Pu Xiao, Jing Zhang (Eds.

)
3D Printing with Light
Also of interest
Green Electrospinning
Horzum, Demir, Muñoz-Espí, Crespy (Eds.), 
ISBN ----, e-ISBN ----

Biocidal Polymers
Pal Singh Chauhan (Ed.), 
ISBN ----, e-ISBN ----

Bioresorbable Polymers
Biomedical Applications.
Devine (Ed.), 
ISBN ----, e-ISBN ----

Nanocellulose
From Nature to High Performance Tailored Materials.
Dufresne, 
ISBN ----, e-ISBN ----

Superabsorbent Polymers
Chemical Design, Processing and Applications.
Van Vlierberghe, Mignon, 
ISBN ----, e-ISBN ----
3D Printing with
Light

Edited by
Pu Xiao and Jing Zhang
Editors
Dr. Pu Xiao
Research School of Chemistry
Australian National University
Canberra, ACT 2601
Australia
[email protected]

Dr. Jing Zhang

Department of Chemical Engineering
Monash University
Clayton, Victoria 3800
Australia
[email protected]

ISBN 978-3-11-056947-6
e-ISBN (PDF) 978-3-11-057058-8
e-ISBN (EPUB) 978-3-11-056984-1

Library of Congress Control Number: 2021930972

Bibliographic information published by the Deutsche Nationalbibliothek

The Deutsche Nationalbibliothek lists this publication in the Deutsche Nationalbibliografie;
detailed bibliographic data are available on the Internet at http://dnb.dnb.de.

© 2021 Walter de Gruyter GmbH, Berlin/Boston

Cover image: Scharfsinn86/iStock/Getty Images Plus
Typesetting: Integra Software Services Pvt. Ltd.
Printing and binding: CPI books GmbH, Leck

www.degruyter.com
Preface
3D printing, different from traditional subtractive manufacturing techniques, is an
additive manufacturing technology in which objects can be produced through com-
puter-aided design without the need of molds. Since its invention in the last cen-
tury, this promising technology has developed rapidly and has found numerous
applications in various fields, ranging from personalized consumer products and
food industry to drug delivery and tissue engineering and so on. Particularly, this
versatile technology has also been used to produce personal protective equipment
(e.g., face shields), medical devices (e.g., ventilator valves) and isolation wards to
fight against the ongoing coronavirus pandemic.
Among various 3D printing approaches (e.g., selective laser sintering, fused de-
position modeling, direct metal laser sintering, electron beam melting and stereoli-
thography), the one based on photopolymerization, that is, polymerization reactions
induced by light, is extremely attractive. In this approach, objects with well-defined
structures can be created from the photopolymerization of liquid photocrosslinkable
resin during light irradiation controlled by computer-aided design models. While
the engineering, electronic and optical technologies of this 3D printing approach
are almost mature, the design and development of high-performance printable
materials/inks remains a key challenge. This book thus aims to provide the recent
progress in the aspects of chemistry and materials of 3D printing with light.
Specifically, Chapter 1 contains information on the recently developed high-
performance photoinitiating systems applicable to the vat photopolymerization 3D
printing technology. Chapter 2 introduces the newly developed two-photon photo-
initiators and their applications in 3D printing and mircofabrication. Chapter 3 criti-
cally reviews the recent advancements in the use of dyes in light-induced 3D printing.
In particular, functional dyes can be exploited to create stimuli-responsive 3D-shaped
polymers. Chapter 4 discusses the role of resin composition for the stereolithographic
3D printing of microfluidic devices, with a specific focus on the methods to success-
fully print enclosed channels of comparable dimensions to existing microfluidic
technologies. The performance of printed objects in microfluidic applications is
also reviewed. Chapter 5 discusses novel 3D printable photopolymerizable bioma-
cromolecules and their applications in 3D printing of biomaterials, which demonstrate
significant potential for clinical diagnosis and therapeutics. Chapter 6 introduces
the principle, development and applications of photocurable 3D printing technology
on the market, and puts forward some key problems of the technique which are re-
quired to be solved. Chapter 7 discusses the dual wavelength photochemistry for the
polymerization reactions and the application in photocuring 3D printing. Chapter 8
introduces a 3D nanoprinting technique based on two-photon photopolymerization,
which has been widely used to fabricate various functional micro-/nanodevices.
Chapter 9 is dedicated to the application of photocontrolled reversible addition frag-
mentation chain transfer polymerization (photoRAFT) in 3D printing, which can add

https://doi.org/10.1515/9783110570588-202
VI Preface

a new dimension to the current manufacturing technologies. Chapter 10 discusses

the main challenges in 3D printing focusing on printing speed and applications in
biomedical areas.
Finally, we would like to thank all chapter authors and De Gruyter, especially
those who have been significantly impacted by the coronavirus pandemic in differ-
ent cities around the world, for their efforts and contributions to the book in this
challenging and tough time. Nothing lasts forever, even the worst disasters must
end some day. Until the day when nature and science shall bring the disasters to
the end, all human wisdom is summed up in two words: wait and hope (Alexandre
Dumas).
Pu Xiao and Jing Zhang
Melbourne, Australia
February 2021
Contents
Preface V

List of contributing authors IX

D. Zhu, J. Zhang, J. Lalevée, P. Xiao

Chapter 1
Novel photoinitiating systems for 3D printing 1

Shixiong Chen, Ruchun Zhou, Ming Jin

Chapter 2
New free radical and cationic photoinitiators for two-photon 3D printing 49

Ignazio Roppolo, Annalisa Chiappone

Chapter 3
Functional dyes in light-induced 3D printing 107

Lubna Shahzadi, Feng Li, Fernando Maya Alejandro, Michael C. Breadmore,

Stuart C. Thickett
Chapter 4
Resin design in stereolithography 3D printing for microfluidic
applications 135

Xiao Chen, Mengfan Zhang, Tingting Wan, Penghui Fan, Kai Shi,
Yingshan Zhou, Weilin Xu, Pu Xiao
Chapter 5
3D printing of biomaterials 175

Xiaoqun Zhu, Guoqiang Lu, Jun Nie

Chapter 6
Photopolymerization and its application in 3D printing of customized
objects 203

Yang-Yang Xu, Zhaofu Ding, Haibin Zhu, Yijun Zhang, Pu Xiao, Jean Pierre
Fouassier, Jacques Lalevée
Chapter 7
Dual wavelength systems in 3D printing 231
VIII Contents

Xuewen Wang, Yunfan Yue, Nianyao Chai, Yibing Chen

Chapter 8
Functional 3D nanoprinting via femtosecond laser nonlinear lithography 249

Ali Bagheri, Jianyong Jin

Chapter 9
3D printing mediated by photoRAFT polymerization process 295

H. Lai, P. Xiao
Chapter 10
Main challenges in 3D printing: printing speed and biomedical
applications 317

Index 335
List of contributing authors
Fernando Maya Alejandro Yibing Cheng
Australian Centre for Research on Separation Foshan Xianhu Laboratory of the Advanced
Science (ACROSS) Energy Science and Technology
University of Tasmania Guangdong Laboratory
Hobart TAS 7001 Foshan 528216
Australia People’s Republic of China

Ali Bagheri State Key Laboratory of Advanced Technology

School of Science and Technology for Materials Synthesis and Processing
The University of New England Wuhan University of Technology
Armidale NSW 2351 Wuhan 430070
Australia People’s Republic of China
[email protected]
Annalisa Chiappone
Michael C. Breadmore Department of Applied Science and
Australian Centre for Research on Separation Technology DISAT
Science (ACROSS) Politecnico di Torino
University of Tasmania Corso Duca degli Abruzzi, 24
Hobart TAS 7001 Torino 10129
Australia Italy

Nianyao Chai Zhaofu Ding

International School of Materials Science and College of Chemistry and Materials Science
Engineering Anhui Normal University
Wuhan University of Technology South Jiuhua Rd. 189
Wuhan 430070 Wuhu 241002
People’s Republic of China People’s Republic of China

State Key Laboratory of Advanced Technology

Penghui Fan
for Materials Synthesis and Processing
College of Materials Science and Engineering
Wuhan University of Technology
Wuhan Textile University
Wuhan 430070
Wuhan 430073
People’s Republic of China
People’s Republic of China

Shixiong Chen
Jean Pierre Fouassier
Department of Polymer Materials
Université de Haute-Alsace
School of Materials Science and Engineering
France
Tongji University
4800 Caoan Road
Jianyong Jin
Shanghai 201804
School of Chemical Sciences
People’s Republic of China
The University of Auckland
Auckland 1010
Xiao Chen
New Zealand
College of Materials Science and Engineering
Wuhan Textile University
Wuhan 430073
People’s Republic of China

https://doi.org/10.1515/9783110570588-204
X List of contributing authors

Ming Jin Ignazio Roppolo

Department of Polymer Materials Department of Applied Science and
School of Materials Science and Engineering Technology DISAT
Tongji University Politecnico di Torino
4800 Caoan Road Corso Duca degli Abruzzi, 24
Shanghai 201804 Torino 10129
People’s Republic of China Italy
[email protected] [email protected]

H. Lai Lubna Shahzadi

Research School of Chemistry Australian Centre for Research on Separation
Australian National University Science (ACROSS)
Canberra, ACT 2601 University of Tasmania
Australia Hobart TAS 7001
Australia
J. Lalevée
Université de Haute-Alsace Interdisciplinary Research Center in
CNRS, Institut de Science des Matériaux de Biomedical Materials
Mulhouse (IS2M) COMSATS University Islamabad
15, rue Jean Starcky Lahore Campus 54000
Cedex 68057 Mulhouse Pakistan
France
[email protected] Kai Shi
College of Materials Science and Engineering
Feng Li Wuhan Textile University
Australian Centre for Research on Separation Wuhan 430073
Science (ACROSS) People’s Republic of China
University of Tasmania
Hobart TAS 7001, Australia Stuart C. Thickett
School of Natural Sciences (Chemistry)
Guoqiang Lu University of Tasmania
College of Materials Engineering and Science Hobart TAS 7001
Beijing University of Chemical Technology Australia
Beijing 100029 [email protected]
People’s Republic of China
Tingting Wan
Jun Nie College of Materials Science and Engineering
College of Materials Engineering and Science Wuhan Textile University
Beijing University of Chemical Technology Wuhan 430073
People’s Republic of China
Beijing 100029
People’s Republic of China
 List of contributing authors XI

Xuewen Wang State Key Laboratory of Advanced Technology

International School of Materials Science and for Materials Synthesis and Processing
Engineering Wuhan University of Technology
Wuhan University of Technology Wuhan 430070
Wuhan 430070 People’s Republic of China
People’s Republic of China
[email protected] J. Zhang
Department of Chemical Engineering
Foshan Xianhu Laboratory of the Advanced Monash University
Energy Science and Technology Clayton, Victoria 3800
Guangdong Laboratory Australia
Foshan 528216
People’s Republic of China Mengfan Zhang
College of Materials Science and Engineering
State Key Laboratory of Advanced Technology
Wuhan Textile University
for Materials Synthesis and Processing
Wuhan 430073
Wuhan University of Technology
People’s Republic of China
Wuhan 430070
People’s Republic of China
Yijun Zhang
Université de Haute-Alsace
P. Xiao
CNRS, Institut de Science des Matériaux de
Research School of Chemistry
Mulhouse (IS2M)
Australian National University
15, rue Jean Starcky
Canberra, ACT 2601
Cedex 68057 Mulhouse
Australia
France
[email protected]

Weilin Xu Ruchun Zhou

State Key Laboratory of New Textile Materials Department of Polymer Materials
and Advanced Processing Technologies School of Materials Science and Engineering
Wuhan Textile University Tongji University
Wuhan 430073 4800 Caoan Road
People’s Republic of China Shanghai 201804
People’s Republic of China
Yang-Yang Xu
College of Chemistry and Materials Science Yingshan Zhou
Anhui Normal University College of Materials Science and Engineering
South Jiuhua Rd. 189 Wuhan Textile University
Wuhu 241002 Wuhan 430073
People’s Republic of China People’s Republic of China
[email protected]
State Key Laboratory of New Textile Materials
and Advanced Processing Technologies
Yunfan Yue Wuhan Textile University
International School of Materials Science and Wuhan 430073
Engineering People’s Republic of China
Wuhan University of Technology [email protected]
Wuhan 430070
People’s Republic of China
XII List of contributing authors

D. Zhu Xiaoqun Zhu

Research School of Chemistry College of Materials Engineering
Australian National University and Science
Canberra, ACT 2601 Beijing University of Chemical Technology
Australia Beijing 100029
People’s Republic of China
Haibin Zhu
College of Chemistry and Materials Science
Anhui Normal University
South Jiuhua Rd. 189
Wuhu 241002
People’s Republic of China
D. Zhu, J. Zhang, J. Lalevée, P. Xiao
Chapter 1
Novel photoinitiating systems for 3D printing
The photosensitive formula for one-photon and two-photon 3D printing consists
of photoinitiating system (PIS) and photocurable monomers/oligomers [1, 2]. PIS
refers to the components group that is irradiated directly by light and produces
active initiating species (free radicals and/or cations) [1, 2]. In more detail, photo-
initiator (PI) is excited by photons, then either homocleaved into free radicals or
reacted with additives via oxidation and energy transfer to generate radicals and/
or cations for polymerization initiation [1, 3]. Therefore, the properties of PIs in
terms of functional group conversion (FC), rate of polymerization (RP,max), color,
transparency and photobleaching affect toughness of 3D printed objects and 3D
printer parameters such as printing layer thickness and printing duration for each
layer [2].
Commercial photoinitiators, 2,4,6-trimethylbenzoyldiphenyl phosphine oxide
(TPO), phenylbis(2,4,6-trimethyl-benzoyl)phosphine oxide (BAPO), (1-hydroxycy-
clohexyl)(phenyl)methanone (Irgacure 184), 2-benzyl-2-(dimethylamino)-1-(4-mor-
pholinophenyl)butan-1-one (Irgacure 369), etc., are efficient and commonly used in
PISs for 3D printing [4]. However, 3D printing technology has been applied to various
fields such as tissue engineering, oral drug production, electrically conductive con-
structs, etc. [5–23]. Commercial PISs have obvious drawbacks such as UV initiation,
toxicity and low efficiency in further advanced use of 3D printing technology. To im-
prove the efficiency of PISs, and to fit low intensity commercial 3D printer projector
in order to meet the standards in some special fields (e.g., medicine, scaffolds, etc.),
additional requirements (e.g., non-toxic, visible-light initiable and highly efficient)
have to be considered. Tons of efficiently designed type I and type II photoinitiators
for 3D printing have been reported (e.g., metal complexes, flavone derivatives and
naphthalimide derivatives) [24–26]. In this chapter, an overview of the newly devel-
oped PISs of centimeter-scale and nanoscale 3D printing are discussed. Guidance on
how to evaluate if a PI or a PIS is suitable for 3D printing is provided as well.

D. Zhu, P. Xiao, Research School of Chemistry, Australian National University, Canberra,

Australia
J. Zhang, Department of Chemical Engineering, Monash University, Clayton, Victoria, Australia
J. Lalevée, Université de Haute-Alsace, CNRS, Institut de Science des Matériaux de Mulhouse
(IS2M), Mulhouse, France

https://doi.org/10.1515/9783110570588-001
2 D. Zhu et al.

1.1 Novel photoinitiating systems in 3D printing

1.1.1 Naturally originated and derived photoinitiators

Due to abundant brightly colored substances (i.e., dyes), nature is a large provider of
potential PIs that are sensitive to visible light LEDs exposure. For instance, curcumin,
a bright yellow turmeric extract, has been observed to be a blue-light-sensitive PI
[27]; riboflavin, also called vitamin B, is another well-investigated natural PI under
blue lights [28, 29]. Several naturally originated and derived compounds have been
reported to be efficient PIs [30–36]. Flavone and coumarin derivatives are presented
in this subsection to introduce their properties and abilities for 3D printing.

1.1.1.1 Flavone-derivative-based photoinitiating systems

Flavone derivatives reported as antioxidants [37] have been discovered to be a new

series of blue-light-sensitive PIs in recent years [24, 38]. A general mechanism of pho-
toinitiation process was proposed [24, 38]. Specifically, flavones are excited to singlet
or triplet state by photons (r1) and then reacted with NPG or Iod forming intermediate
free radicals (r2–r4). An alternate route is two additives (i.e., NPG and Iod) interact
and produce a charge transfer complex (CTC) (r5). This CTC can then be decomposed
to phenyl radicals (Ar•) (r6). The Ar• is then initiated the following polymerization:

Flavone ! 1,3 FlavoneðhνÞ (r1)

1,3
Flavone + NPG ! NPGð− HÞ • + Flavone − H• (r2)

NPGð− HÞ • ! CO2 + NPGð− H, − CO2Þ • (r3)

1,3
Flavone + Ar2 I + ! Flavone• + + Ar• + Ar − I (r4)

NPG + Iod ! ½NPG − IodCTC (r5)

½NPG − IodCTC ! ! ! Ar• ðhνÞ (r6)

Photoinitiators
3-Hydroxyflavone (3HF), 6-hydroxyflavone (6HF) and 7-hydroxyflavone (7HF) (Scheme 1.1)
are monohydroxy-substituted flavone derivatives. Chrysin and myricetin (Scheme 1.1)
are multi-hydroxyl-substituted flavone derivatives. Of all, myricetin is the reddest
shifted compound in terms of light absorption among reported flavone derivatives
(Table 1.1: λmax = ∼375 nm). All presented flavone derivatives have no maximum ab-
sorption peak in visible light range, but their light absorption profiles overlap with
the emission profile of LED@405 nm, and the corresponding extinction coefficients
 Chapter 1 Novel photoinitiating systems for 3D printing 3

O O HO O

OH HO
O O O
3-Hydroxyflavone 6-Hydroxyflavone 7-Hydroxyflavone

OH
OH

HO O HO O O
OH
OH
OH O OH O O
Chrysin Myricetin Flavone

Scheme 1.1: Chemical structures of flavone derivatives.

Table 1.1: Light absorption properties of flavone derivatives in methanol: maximum absorption
wavelength (λmax), molar extinction coefficients at λmax and at the maximum LEDs emission
wavelengths (εLED) of irradiation sources.

PI λmax (nm) εmax (M− cm−) ε nm (M− cm−) Ref.

Flavone -* -* ~ []

HF ~ ~, ~ []
HF -* -* ~ []
HF ~ ~, ~ []
Chrysin ~ ~, ~ []
Myricetin  , , []

*:no obvious maximum absorption peak.

are listed in Table 1.1. Monohydroxy- and dihydroxy-substituted flavones exhibit

extinction coefficients at used LED@405 nm as ∼70 M−1 cm−1–∼450 M−1 cm−1,
while the hexahydroxy substituted flavones, myricetin, has the extinction coeffi-
cient of 4,800 M−1 cm−1 at 405 nm.
Non-hydroxy substituted flavone (i.e., flavone itself) can trigger free radical
polymerization of methacrylates (bisphenol-A-glycidyl methacrylate (Bis-GMA)
and trethylene glycol dimethacrylate (TEGDMA), 70 wt%/30 wt%) but cannot pro-
mote the polymerization propagation (double bond functional group conversion
(FC) of methacrylates at 100-s irradiation is only 4%). 3HF exhibits minor extinction
coefficient at 405 nm in methanol (ε405 nm = ∼250 M−1 cm−1). In addition of the amine,
N-phenylglycine (NPG), 3HF-based PIS can efficiently initiate photopolymerization
of the blend of Bis-GMA/TEGDMA (thickness = 1.4 mm) under the irradiation of
LED@405 nm. The double bond conversion of these methacrylates is 71% at 100-s
4 D. Zhu et al.

irradiation (Table 1.2). In the same conditions as 3HF-based PIS, 6HF- and 7HF-based
PISs initiate the blend of Bis-GMA/TEGDMA quite less than 3HF-based two-component
PIS (FCt = 100 s(6HF/NPG) = 43%; FCt = 100 s(7HF/NPG) = 31.3%), illustrating that the
location of substituents affects a flavone’s photophysics and photoinitiation abili-
ties (Tables 1.1 and 1.2). 20% and 0% methacrylates conversion were attained using
PISs of chrysin/NPG and myricetin/NPG, respectively, although the myricetin ab-
sorbs the most photon at 405 nm irradiation (ε405 nm = 4,800 M−1 cm−1) (Table 1.1
and 1.2). This might be ascribed to the number of the hydroxyl group. Hydroxyl
group is a common radical scavenger that can catch free radicals and prevent active
radicals from initiating polymerization [39]. Therefore, the multi-hydroxy flavone,
myricetin, can hardly initiate photopolymerization of methacrylates in the presence
of NPG upon exposure to LED@405 nm (Table 1.2 and Figure 1.1(a)).

Table 1.2: Functional group conversion (FC) of Bis-GMA/TEGDMA (70%/30%, w/w), when using
diverse photoinitiating systems (0.5 wt% PI/1 wt% NPG, thickness = 1.4 mm) under air upon
exposure to LED@405 nm (I0 = 110 mW cm−2) at 100 s [24, 38].

PIS Flavone/NPG HF/NPG HF/NPG HF/NPG Chrysin/NPG Myricetin/NPG

FC (%)    .  n.p.a

a
n.p.: no polymerization

Additives
Two monohydroxy flavones, 3HF and 6HF, were chosen as target PIs for 3D printing
due to their relatively high efficiency in the presence of NPG in free radical photopoly-
merization of methacrylates studies, as shown in Table 1.2 and Figure 1.1(a). As stated,
the discussed flavone derivatives enclosed in Scheme 1.1 are type II PIs. Different addi-
tives can affect the photoinitiation ability of flavone derivatives positively or negatively,
to various levels (Table 1.3 and Figure 1.1(b)). The effect of additives on NPG, diphe-
nyliodonium hexafluorophosphate (Iod), ethyl 4-(dimethylamino)benzoate (EDB) and
4-diphenylphosphinobenzoic acid (4-DPPBA) were investigated. As for 3HF, PISs in
the presence of NPG alone and Iod/NPG presented efficiency in free radical polymeri-
zation of methacrylates (Table 1.3: FCt = 100 s(3HF/NPG) = 71%, FCt = 100 s(3HF/Iod/
NPG) = 79%, while FCt = 100 s(3HF/Iod/EDB) is only 17%). The Iod/NPG is the best ad-
ditives combination among studied PISs, though NPG alone can improve 3HF photo-
initiation ability excellently (Table 1.3). Therefore, 3HF/NPG (0.5%/1%, wt) in the
blend of Bis-GMA/TEGDMA (70%/30%, wt) was then prepared as 3D printing resin.
As shown in Table 1.3, 6HF-based PISs were studied in two monomer systems –
a blend of Bis-GMA/TEGDMA (70%/30%, wt) and trimethylolpropane triacrylate
(TMPTA) alone. In photopolymerization of the blend of Bis-GMA/TEGDMA, additive
combinations Iod/NPG and Iod/EDB in the presence of 6HF gave the highest double
 Chapter 1 Novel photoinitiating systems for 3D printing 5

(a)
50

40 1 1. 6HF/NPG (0.5/1wt%). LED@405 nm.

Conversion (%)

2. Chrysin/NPG (0.5/1wt%). LED@405 nm.

30 4 3. Myricetin/NPG (0.5/1wt%). LED@405 nm.
2 4. 7HF/NPG (0.5/1/1wt%). LED@405 nm.
20
5. Flavone/NPG (0.5/1wt%). LED@405 nm.
10 6. NPG (1 wt%). LED@405 nm.
5 6
0 3
0 50 100
Time (s)
(b)
1. 6HF/lod/NPG (0.5/1/1wt%). LED@405 nm.
80 (1)
2. 6HF/NPG (0.5/1wt%). LED@405 nm.
70 (5)
3. 6HF/lod/EDB (0.5/1/1wt%). LED@385 nm.
Conversion (%)

60 (4)
(3) 4. 6HF/lod/EDB (0.5/1/1wt%). LED@405 nm.
50
(2) 5. lod/NPG (0.5/1wt%). LED@405 nm.
40 (10) 6. 6HF/lod (0.5/1wt%). LED@385 nm.
30 (6) 7. 6HF/lod (0.5/1wt%). LED@405 nm.
20 8. 6HF/EDB (0.5/1wt%). LED@405 nm.
(7)
10 9. lod/EDB (1/1 wt%). LED@405 nm.
(8)
0 (9) 10. NPG (1 wt%). LED@405 nm.
0 10 20 30 40 50 60 70 80 90 100
Time (s)

Figure 1.1: Photopolymerization of Bis-GMA/TEGDMA (70%/30%, wt, thickness = 1.4 mm) (FC vs.
time) under air in presence of (a) flavone derivatives/NPG and (b) 6HF/additives upon exposure to
LED@405 nm and/or LED@385 nm [38]. Reproduced with permission from [38]. Copyright 2020
Wiley Periodicals, Inc.

Table 1.3: Photopolymerization of Bis-GMA/TEGDMA (70%/30%, wt, thickness = 1.4 mm) at 100 s
and TMPTA (thickness = 25 µm) under air at 200 s in the presence of flavone derivatives and
diverse additive combinations upon exposure to LED@405 nm [24, 38].

PI Additives

NPG Iod EDB Iod/NPG Iod/EDB Iod/-DPPBA

HF(DR ) a
% – – % % b
–
HF(DRa) % .% % .% .% –
HF(TMPTA) .% c  %c .%c %b,c
a
: DR: dental resin, Bis-GMA/TEGDMA (70%/30%, wt)
b
: irradiation at 385 nm
c
: in laminate
6 D. Zhu et al.

bond conversion of methacrylates (FCt = 100 s(6HF/Iod/NPG) = 78.4%, FCt = 100 s

(6HF/Iod/EDB) = 56.6%) (Table 1.3). While using TMPTA as monomers, Iod/4-
DPPBA and Iod/NPG are two efficient additive combinations in the presence of
6HF (FCt = 100 s(6HF/Iod/4-DPPBA) = 43%, FCt = 100 s(6HF/Iod/NPG) = 40%) (Table 1.3).
This is ascribed to the viscosity of the blend of Bis-GMA/TEGDMA. Viscous monomer
prevents oxygen diffusion and reduces oxygen inhibition in free radical poly-
merization [40].

3D printing
After confirming the components of 3D printing resin, the 3HF/NPG (0.5%/1%, wt) and
6HF/Iod/4-DPPBA that demonstrated high initiation efficiency to methacrylates were
used as PISs in 3D printing. Figure 1.2 presents 3D printed objects and their characteri-
zation by numerical optical microscopy. Figure 1.2(A, B) show the 3D printed logo “nat-
ural.” The thickness of the 3D printed object is 1.9 mm according to profilometry of
numerical optical microscopy (Figure 1.2(C)). Figure 1.2(a, b) show the 3D printed letter
“n” and a cube. The thickness of the 3D printed “n” is 30 μm, and the thickness of the
3D printed cube is 1.8 mm, according to profilometry of numerical optical microscopy
(Figure 1.2(c, d)). Among presented flavone derivatives, 3HF/NPG, 3HF/Iod/NPG and
6HF/Iod/NPG and 6HF/Iod/4-DPPBA are promising PISs for 3D printing.

1.1.1.2 Coumarin-derivative-based photoinitiating systems

Photophysical properties
Various coumarin derivatives have been explored as UV-sensitive or blue-light-
sensitive photoinitiators for both free radical and cationic polymerization [41, 42]. An
oxime-ester coumarin has also been introduced to upconversion nanoparticles as a
near-infrared photoinitiator for free radical polymerization [43]. The coumarin deriva-
tives shown in Scheme 1.2 have turned out to be efficient in blue-light-initiating 3D
printing technology [44, 45]. As presented in Table 1.4, the most listed coumarin de-
rivatives exhibit light absorption maxima above 400 nm (except for λmax(KC-E) =
343 nm, λmax(KC-G) = 294 nm and λmax(KC-H) = 349 nm). Even though KC-E and KC-G
presented light absorption maxima in UV range, their light absorption profile con-
tained a tail above 400 nm [44]. The order of magnitude of the extinction coefficients
at their absorption maxima (for all) and at 405 nm is 4 (for all but ε405 nm(KC-E) =
260 M−1 cm−1, ε405 nm(KC-G) = 160 M−1 cm−1 and ε405 nm(KC-H) = 3,260 M−1 cm−1)
(Table 1.4). A few possible effects of functional group on absorption maxima in UV
range can be discovered from Scheme 1.2 and Table 1.4: comparing KC-F with KC-G,
the diethyl amine substitution in KC-F can red shift the light absorption profile; when
comparing KC-C and KC-E, the methoxyl group instead of diethyl amine group offers
the same results as KC-C in blue shifting; all three compounds with absorption maxima
 Chapter 1 Novel photoinitiating systems for 3D printing 7

Figure 1.2: 3D printed object using 3HF/NPG (A-C) and 6HF/Iod/4-DPPBA (a-d) under irradiation of
LED@405 nm [24, 38]. Adapted with permission from [24, 38]. Copyright 2018 American Chemical
Society and Copyright 2020 Wiley Periodicals, Inc.
8 D. Zhu et al.

in UV range are in the absence of diethyl amine substitution (KC-E, KC-G and KC-H) at
coumarin moiety. A reasonable deduction is that the presence of diethyl amine substi-
tute in KC-C and KC-F can induce red-shifted light absorption.

Photoinitiation abilities
Photoinitiation abilities of coumarin derivatives (Scheme 1.2) in the presence of Iod
and/or NPG were illustrated via polymerization of TMPTA (thickness = 1.4 mm)
under air with irradiation of LED@405 nm (Table 1.5). For two-component PISs
(with Iod or NPG), Coum-A1 and KC-H are ineffective (no polymerization detected)
for free radical polymerization of TMPTA under the stated conditions (Table 1.5 cap-
tion). This can be ascribed to photoinitiation abilities – the limited light penetration
due to the thickness of sample and the oxygen inhibition effect due to the under air
condition – which was validated by the fact that the same PISs (Coum-A1/Iod,
Coum-A1/NPG and KC-H/NPG) can effectively initiate polymerization of TMPTA
(thickness = 25 μm) in laminate [44].
As for PISs of coumarin derivatives in the presence of Iod (Table 1.5), KC-E/
Iod PIS-initiated polymerization of TMPTA ended at 100 s with FC = 37%; CoumA/
Iod PIS gave increase in FC of TMPTA to 45%; KC-G/Iod led to no polymerization
initiation. The other two-component PISs (CoumB/Iod, KC-C/Iod, KC-D/Iod and
KC-F/Iod) brought FC within the range of ∼58% to ∼70%. In addition to Iod, NPG
was also investigated as an additive to coumarin derivatives. As presented in
Table 1.5. Thiophene (derivatives)-substituted coumarins, CoumA or CoumB, in
the presence of NPG showed no effect on polymerization of TMPTA (FC = 0%)
(Table 1.5). Benzophenone (derivatives)-substituted coumarins, KCs, presented
more efficient photoinitiation abilities with NPG, compared to Iod (Table 1.5).
NPG, in place of Iod, increased FC of TMPTA by ∼10% for KC-C, KC-D and KC-F,
while it increased FC incredibly for KC-E-based two-component PIS in TMPTA by
49%, and for KC-G-based two-component PIS in TMPTA, from no polymerization
to FC = 78% (Table 1.5).
When combining Iod and NPG with coumarin derivatives as three-component
PISs, the presence of two additives enhanced photoinitiation abilities of coumarin
derivatives or at least retained the effectiveness, when using corresponding two-
component PISs (Table 1.5). All coumarin-derivative-based three-component PISs,
except for Coum-A1- and KC-H-based PISs, can efficiently initiate polymerization
of TMPTA. As for CoumB/Iod/NPG in Table 1.5, the FC(TMPTA) = 93%. Other effective
coumarin-derivative-based three-component PISs can initiate photopolymerization
of TMPTA with high double bond conversions from 79% to 86% (Table 1.5).

3D printable resins and 3D printing

Besides TMPTA, the blend of Bis-GMA/TEGDA (70%/30%, wt) was also used for 3D
printing with coumarin-derivative-based PISs. As shown in Table 1.5, Iod-added
Chapter 1 Novel photoinitiating systems for 3D printing 9

Scheme 1.2: Chemical structures of coumarin derivatives.

10 D. Zhu et al.

Table 1.4: Light absorption properties of coumarin derivatives: maximum absorption wavelength
(λmax), molar extinction coefficients at λmax and at the maximum LED@405 nm emission
wavelengths (ε405 nm) of irradiation sources.

PI λmax (nm) εmax (M− cm−) ε nm (M− cm−) ref

CoumA  , , []

CoumB  , , []
Coum-A  , , []
Coum-B  , , []
KC-C  , , []
KC-D  , , []
KC-E  ,  []
KC-F  , , []
KC-G  ,  []
KC-H  , , []

Table 1.5: Functional group conversion of TMPTA for 100-s irradiation and Bis-GMA/TEGDMA (70%/
30%, wt) for 150-s irradiation under air upon exposure to LED@405 nm in the presence of
coumarin-derivative-based PISs (PI: 0.2 wt%, Iod: 1 wt%, NPG: 1 wt%; thickness = 1.4 mm) [44, 45].

PI Monomer + additives

TMPTA Bis-GMA/TEGDMA

Iod NPG Iod/NPG Iod NPG Iod/NPG

CoumA % n.p.a

% % n.p.a
%
CoumB % n.p.a % % n.p.a %
Coum-A n.p.a n.p.a n.p.a – – –
Coum-B – – % – – –
KC-C % % % – – –
KC-D % % % – – –
KC-E % % % – – –
KC-F % % % – – –
KC-G n.p.a % % – – –
KC-H n.p.a n.p.a n.p.a – – –
a
n.p.: no polymerization

CoumA- and CoumB-based two-component PISs can effectively initiate polymerization

of Bis-GMA/TEGDA (FC(CoumA/Iod)t = 100 s = 36%; FC(CoumB/Iod)t = 100 s = 57%).
Although another additive, NPG, has no effect on CoumA- and CoumB-based two-
component PISs initiating polymerization of Bis-GMA/TEGDA (70%/30%, wt), the ad-
dition of NPG can enhance the CoumA or CoumB/Iod PIS photoinitiation abilities
(Table 1.5). Specifically, the double bond conversions of Bis-GMA/TEGDMA are 69%
and 74% for CoumA/Iod and CoumB/Iod, respectively, in the presence of NPG, while
they are 36% and 57% correspondingly in the absence of NPG (Table 1.5). With the
 Chapter 1 Novel photoinitiating systems for 3D printing 11

results of polymerization of TMPTA and Bis-GMA/TEGDMA, further letter patterns are

3D printed using LED@405 nm under air. The letter patterns shown in Figure 1.3 used
two- and three-component PISs (CoumA(B)/Iod, CoumA(B)/Iod/NPG, KC-C/NPG and
KC-C(D)/Iod/NPG) to initiate 3D photocuring of TMPTA and Bis-GMA/TEGDMA; and

Figure 1.3: Characterization of 3D printed object by numerical optical microscopy using CoumA- and
CoumB-based PISs (A-I) and KCs-based PISs (a-c) under irradiation of LED@405 nm: (A) CoumB/Iod/
NPG (0.012%/0.061%/0.061% w/w) in Bis-GMA/TEGDMA (thickness = 1,880 µm); (B) CoumA/Iod/
NPG (0.025%/0.125%/0.125% w/w) in Bis-GMA/TEGDMA (thickness = 2,200 µm); (C) CoumA/Iod
(0.04%/0.2% w/w) in (3,4-epoxycyclohexane)methyl 3,4-epoxycyclohexylcarboxylate (EPOX)/TMPTA
(thickness = 2,340 µm); (D) CoumA/Iod (0.05%/0.25% w/w) in TMPTA (thickness = 2,420 µm);
(E) CoumB/Iod (0.015%/0.077% w/w) in BisGMA/TEGDMA (thickness = 2,460 µm); (F) CoumA/Iod
(0.04%/0.2% w/w) in TMPTA (thickness = 2,840 µm); (G) CoumB/Iod/NPG (0.018%/0.091%/0.091%
w/w) in TMPTA (thickness = 2,400 µm); (H) CoumA/Iod/NPG (0.02%/0.1%/0.1% w/w) in TMPTA
(thickness = 3,200 µm); (I) CoumB/Iod (0.05%/0.025% w/w) in TMPTA (thickness = 2,620 µm);
(a) KC-D/Iod/NPG (0.02%/0.1%/0.1% w/w) in TMPTA (thickness = 2,220 µm); (b) KC-C/Iod/NPG
(0.016%/0.083%/0.083% w/w) in TMPTA (thickness = 2,220 µm); and (c) KC-C/NPG (0.025%/0.125%
w/w) in TMPTA (thickness = 1,590 µm) [44, 45]. Adapted with permission from [44, 45]. Copyright
2020 Wiley Periodicals, Inc. and Copyright 2019 The Royal Society of Chemistry.
12 D. Zhu et al.

the thickness of the 3D printed patterns range from 1,590 μm to 3,200 μm (Figure 1.3).
All thick patterns were completely printed within 1 min [44, 45].

1.1.2 Carbazole-derivative-based photoinitiating systems

Some commonly used coinitiators or their derivatives later turned out to be efficient
PIS (e.g., NPG derivative: N-phenylglycine-o-carboxylic acid) [33]. A well-known co-
initiator for cationic polymerization initiation is a carbazole derivative (i.e., N-vinyl-
carbazole (NVK)) [31, 36]. A series of carbazole derivatives have been reported as
efficient one-photon PIs and two-photon PIs that initiate polymerization [46, 47].
Recently, some carbazole derivatives were reported as efficient PIs for 3D printing
(Scheme 1.3) [48–51]. All the presented carbazole derivatives illustrate absorption
maxima in UV range (Figure 1.4).

1.1.2.1 Carbazole-oxime-esters: for both one-photon and two-photon 3D printing

Carbazole-oxime-esters (4a–4d) (Scheme 1.3) showed light absorption at 405 nm

(Figure 1.4), and the oxime-ester moiety provides them with the capability of two-
photon polymerization (TPP) initiation [52, 53]. The free radical of 4d trapped by
PBN was generated by light excitation, indicating that investigated carbazole-oxime-
esters can initiate polymerization as a one-component PI [52].
These four compounds as one-component PIs can efficiently initiate polymeriza-
tion of TMPTA/ethoxylated trimethylolpropane triacrylate (TMP3EOTA) (1:1, equality
of functional groups) upon LED@405 nm (45 mW cm−2) in the absence of air (double
bond FC: 40%–60%) [52]. Among these, 4b and 4d were comparable to 2,4,6-
trimethylbenzoyldiphenyl phosphine oxide (TPO) [52]. 4d was chosen as PI for
one-photon digital light process (DLP) 3D printing (Figure 1.5). The resolution of 3D
printed deer figurine (Figure 1.5(a)) is 50 μm [52]. The deer were printed in high fidelity,
which is validated by the vertical view of deer antler in Figure 1.5(b). Figure 1.5(c, d)
reveal the deviation between printed object and designed model. According to the
color band in Figure 1.5(d), the green part indicates the deviation is within ± 0.1 mm.
The more reddish and the more bluish mean that the absolute deviation is larger.
Therefore, it was proved that 4d could produce a precise 3D printed object, limiting the
deviation to 0.1 mm.
As for two-photon 3D printing initiated by carbazole-oxime-esters, the σ2PA of
4a–4d at 800 nm was investigated via z-scan technique [52]. Due to presence of the
electron donating group (EDG) and electron withdrawing group (EWG) in carba-
zole-oxime-ester structure, the two-photon cross section (σ2PA, 800 nm) of 4a–4d
are higher than a reported efficient two-photon PI, and the laser transmittance of
4d in chloroform is the highest among the same concentration of 4a–4d [52, 54].
 Chapter 1 Novel photoinitiating systems for 3D printing

Scheme 1.3: Chemical structures of investigated carbazole derivatives.

13
14 D. Zhu et al.

Figure 1.4: Light absorption maxima and extinction coefficients at maxima of carbazole derivatives
(bubble size: extinction coefficient) [48–51].

1.1.2.2 Other carbazole derivatives: for one-photon 3D printing

In Scheme 1.3, the other compounds (i.e., A1–A4, Cd1–Cd7 and C1–C4) are used in
multicomponent PISs. Their light absorption maxima present within UV range of
320 nm–390 nm (Figure 1.4). However, they illustrate light absorption at 405 nm
with other magnitude of molar extinction coefficients from 2 to 5 (except for Cd2
and Cd6 in Figure 1.4), which is the irradiation wavelength of the projector in the
3D printer that is used [49, 50, 52, 55].
As for free radical polymerization, the photocuring of acrylate (TMPTA) in
the presence of Iod and/or EDB as well as methacrylates (Bis-GMA/TEGDMA) in
the presence of Iod mostly occurred (Table 1.6). While using two-component
PISs, the FC of TMPTA is from 0% to 58% (Table 1.6). The A3/Iod (FCt =100s = 58%),
Cd7/Iod (FCt =100s = 57%) and C2/Iod (FCt =100s = 56%) are the most efficient two-
component PISs in each group (Table 1.6). When EDB, instead of Iod, was added as
the coinitiator in two-component PISs, the FC of TMPTA were less than or, at most,
 Chapter 1 Novel photoinitiating systems for 3D printing 15

(a) (b) (c)

5 mm

(d) 0.200
0.180
0.160
0.140
0.120
0.100

–0.100
–0.120
–0.140
–0.160
–0.180
–0.200
mm

Figure 1.5: (a) 3D printing model of deer; (b) the vertical view of the printed object; (c) 3D printing
model of plant; and (d) 3D scanning picture (4d was used as PI, the wavelength of printer source is
405 nm, and the coin diameter is 25 mm) [48]. Adapted with permission from [48]. Copyright 2020
Wiley‐VCH Verlag GmbH & Co. KGaA, Weinheim.

similar to the FC of TMPTA using Iod as the coinitiator (Table 1.6). The FC differ-
ence between PI/Iod and PI/EDB was from 0% (C3/Iod and C3/EDB) to 19% (A2/Iod
and A2/EDB) (Table 1.6). While using three-component PISs in addition to EDB
to Iod, the FCs of TMPTA were enhanced for all presented PISs (Table 1.6). While
using Bis-GMA/TEGDMA (70%/30%, wt) instead of TMTPA, the double bond
conversion of methacrylate improved by ∼10% for A2/Iod and Cd1/Iod (Table 1.6).
This might be ascribed to less oxygen diffusion due to monomer viscosity [40].
16 D. Zhu et al.

Table 1.6: Photopolymerization of EPOX, acrylates (TMPTA) and methacrylate (Bis-GMA/TEGDMA)

upon exposure to LED@405 nm (110 mW cm−2) under air for 100 s, unless otherwise noted [48–51].

PI Monomer + additives

EPOX Bis-GMA/TEGDMA TMPTA

Iod Iod Iod NPG Iod/NPG

A % a n.p.b,c % d % d % d

A % a % c % d % d % d
A % a – % d % d % d
A % a % d – –
Cd % % c % d – –
Cd n.p. b n.p. b,c n.p. b,d – –
Cd % – % d – –
Cd % – % d – –
Cd % – % d – –
Cd – – % d – –
Cd % % % d – –
C % a – % d % d –
C % a % c % d % d % d
C % a – % d % d –
C % a – % d % d % d
a
: no polymerization
b
: t = 800 s
c
: thickness = 1.4 nm
d
: in laminate

Although the free radical polymerization of TMPTA and Bis-GMA/TEDGMA showed

good efficiency with investigated two- or three-component carbazole-derivatives-based
PISs, the shrinkage effect of polymerization is due to the nature of methacrylates and
acrylates [56, 57]. On the contrary, cationic polymerization of EPOX is a ring-opening
polymerization that shows little shrinkage [58]. Hence, cationic polymerization of
EPOX upon exposure to LED@405 nm under air was performed, and the efficiency
order of carbazole derivatives was: C1 > C4 > C3 > C2 > A2∼A3 > A4∼A1 > Cd7∼Cd1 >
Cd3 > Cd5 > Cd4 > Cd6∼Cd2 (Table 1.6), which aligns with light absorption properties
(Figure 1.4) of ε405 nm(Cd2) = 0 M−1 cm−1 and ε405 nm (Cd6) = 0 M −1 cm−1. Therefore,
two-component PISs in the presence of Iod (1 wt%) with A3, Cd7 or C2 (0.5 wt%) were
then set as PISs for 3D printing [49, 50, 55]. EPOX was used in 3D printing due to its
less shrinkage during polymerization, unlike the free radical polymerization of acryl-
ates and methacrylates [58]. The PISs can apply to a thick layer (thickness = 0.5 mm),
which can reduce overall printing time due to the smallest number of object layers.
 Chapter 1 Novel photoinitiating systems for 3D printing 17

Therefore the printing time was within 1 min, even for a 0.5-mm thick 3D printed
cube [49, 50, 55].

1.1.3 Charge transfer complexes

A number of charge transfer complexes (CTCs) have been found to be efficient in

both visible-light-photoinitiated polymerization – due to their red-shifted light ab-
sorption and allowing extremely deep light penetration (i.e., 31 cm in [59]) – as also
in thermally initiated polymerization [60–64]. The well-investigated CTC combina-
tion is an [amine-iodonium salt]CTC-([donor-acceptor]CTC) combination (e.g., NPG/
Iod) [62]. Chemical structures of discussed CTCs (donors and acceptors) in this
chapter are enclosed in Scheme 1.4.

1.1.3.1 Diverse phenylamines and iodonium salts

NPG was found as a group of [NPG-Iod]CTC that can photoinitiate 9-cm-thick mono-
mer composite [33, 62]. The phenyl amines and tertiary amines were investigated in
PISs for 3D printing (Am1-Am7 in Scheme 1.4) [59]. As presented in Figure 1.6(a),
the obvious red shift was found for [Am1-Iod]CTC through calculation. Meanwhile,
the experimental light absorption profiles (Figure 1.6b) also validated that the CTC

Scheme 1.4: Chemical structures of donors and acceptors in CTCs.

18 D. Zhu et al.

Figure 1.6: (a) Optimized (at the UB3LYP/LANL2DZ level) Am1, Iod, and [Am1-Iod]CTC geometries and
their respective UV-vis spectra (single point in DCM). (b) Experimental UV-vis [59]. Adapted with
permission from [59]. Copyright 2017 American Chemical Society.
 Chapter 1 Novel photoinitiating systems for 3D printing 19

complex of amine in the presence of Iod ([Am1-Iod]C T C CTC curve 3) exhibits light
absorption above 400 nm, up to 550 nm from blue light to green light, while Am1
(curve 1) or Iod (curve 2) alone demonstrate light absorption only within UV range.
This might be ascribed to the HOMO located at electron rich N-aromatic amines and
LUMO located at iodonium salt, inducing lower HOMO-LUMO gap (i.e., ΔE =
3.13 eV) [33, 59]. Due to the drastic red-shift effect, it allowed application of UV-
absorbing PIs to blue-light-triggered 3D printing.

Amines and onium salts: effect on CTC

As NPG/Iod has been investigated as an efficient CTC complex for photopolymeriza-
tion initiation [62], Iod was used as model acceptor for amines in the CTC complex
study. Among Am1-7, Am1/Iod and Am2/Iod were exceptional for FC of resin 1 (1,4-
butanediol dimethacrylate (1,4-BDMA)/hydroxypropyl methacrylate (HPMA)/urethane
dimethacrylate oligomer (33%/33%/33%, wt)) and irradiation time (Table 1.8: FCt = 150 s
(Am1/Iod) = 77% and FCt = 160 s(Am2/Iod) = 71%). This also aligned with their UV-vis
spectra in the presence of Iod: [Am1-Iod]CTC and [Am2-Iod]CTC absorbed the most light
at 405 nm in dichloromethane (DCM) (Ams: 29 mM; Iod: 13.8 mM) [59]. It was noted
that the Iod2 in CTC complexes presented similar results of FCs as did using Iod
(Table 1.8). The author opines that this might be due to the electron donating group
(EDG) located on aromatic ring and increasing electron density on aromatic N atom;
the electron withdrawing group (EWG), ester group on Am3 diluting the electron den-
sity on aromatic N resulted in less red-shift effect and less efficiency on FC and irradia-
tion time (Scheme 1.4 and Table 1.8) [59]. Furthermore, this also aligned with the
results of HOMO energy. Am1 and Am2 have the highest HOMO energy among Am1-
Am7 (HOMO energy (Am1) = HOMO energy (Am2) = –4.84 eV) (Table 1.7), which gave
the lowest HOMO-LUMO gap when using the same acceptor, Iod.

Table 1.7: Summary of donors (amines) HOMO energies in the presence of Iod and acceptors (onium
salts) LUMO energies in the presence of Am1 (calculated at the UB3LYP/LANL2DZ Level) [59].

Amines Am Am Am Am Am Am Am

HOMO energy (eV) −. −. −. −. −. −. −.

Onium salts Iod Iod Iod Iod PSI – –

LUMO energy (eV) −. −. −. −. −. – –

As Am1 showed the best efficiency on FC and irradiation time, it was used as model
donor in acceptor studies. Studied acceptors (i.e., iodonium salts) are presented
in Scheme 1.4. As mentioned, a small HOMO-LUMO gap could induce red-shift ef-
fect for CTC complexes. For donors (i.e., amines), high HOMO energy is attractive,
and for acceptors, low LUMO energy is preferred. As presented in Table 1.7, theoret-
ically, Iod and Iod4 should be more efficient in CTC systems than Iod2 and Iod3 for
20 D. Zhu et al.

their cationic form LUMO energies, which are −6.15 eV and −6.53 eV, respectively.
However, the [Am1-Iod2]CTC molecular orbital property showed a localized LUMO,
and [Am1-Iod]CTC LUMO was somewhat delocalized [59].
Although CTC complexes turned out to be super efficient in deep resin photocur-
ing, thermal free radical polymerization and 3D printing [59, 62], migration issues
due to PI molecular weight remain serious. Therefore, a macro-acceptor (Scheme 1.4),
iodinated polystyrene (PSI), was synthesized and used in CTC complex studies [64].
[Am1-PSI]CTC red-shifted light absorption from range 100–300 nm to range 200–400
nm (λmax = 307 nm) [64]. Irradiation at 405 nm can result in radical generation via
bond photoinduced dehalogenation [64].

Photopolymerization and 3D printing

The photoinitiation abilities of the relevant donor/acceptor/phosphine (1%/2%/
1.5%) as PISs were investigated. The photoinitiation abilities of Iod- and Iod2-based
CTC complexes are pretty similar in the polymerization of resin 1 upon exposure to
LED@405 nm (Table 1.8). As Am1 and Am2 are of similar structure and show similar
photoinitiation abilities in CTC complexes of [amine-onium salt]CTC (Table 1.8), and
as Am2 is less toxic than Am1 according to manufacturer’s data [59], [Am2-Iod2]CTC
was used for the photopolymerization and 3D printing. 4-(Diphenylphosphino)sty-
rene (4dpps) was a phosphine additive in addition to CTC complex ([Am2-Iod2]CTC)
for photopolymerization of resin 1, which shortened the polymerization time from
100 s to 50 s [59]. With Am2/Iod2/4dpps, depth of photopolymerization was investi-
gated with resin 1 and resin 2 (Bis-GMA/TEGDMA: 70%/30%, wt).

Table 1.8: Photopolymerization double bond FC of resin 1 under air in the presence of amine and
Iod or Iod2 upon exposure to LED@405 nm [59].

Donor Am Am Am Am Am Am Am

Accepter Iod

FC (%)       
Irradiation time (s)       

Acceptor Iod

FC (%) ~ ~ ~ ~ ~ ~ ~

Irradiation time (s) ~ ~  ~ ~  ~

According to Raman analysis, the sample depth at 9 cm was of FC(C =C) = ∼40% for
resin 2 within 10 min and of FC(C =C) = ∼60% for resin 1 within 12 min [59]. Moreover,
the deepest cured sample in the presence of Am2/Iod2/4dpps for resin 2 is 31 cm [59].
Such deep photocuring ability provides a broad avenue for application optimization
(e.g., shortening 3D printing time). Using PSI as acceptor, Am1-based CTC complex,
 Chapter 1 Novel photoinitiating systems for 3D printing 21

in the absence of phosphine additive, can result in double bond conversion of

TMPTA of 40% at irradiation time of 100 s [64].
With the same PISs (Am2/Iod2/3dpps: 1%/2%/1.5% and Am1/PSI: 0.5%/1%,
wt), laser-written thick “CTC” and letter “P” were successfully printed in 200-μm
and 96-μm thickness, respectively (laser diode at 405 nm) [59, 64]. The spatial reso-
lution of “CTC” was pretty good as the pattern edge width was only 54 μm [59].

1.1.3.2 Phosphines instead of amines as donors

As mentioned in amine-based donors in CTC complexes, a phosphine additive (i.e.,

4dpps) was used in PISs [59]. Due to lone pairs, phosphine-atom and nitrogen-atom
are promising electron-rich centers (e.g., NPG, Am1 and Am2) [59, 62]. Several phos-
phine-centered compounds were investigated as donors in CTC complexes (Scheme 1.5)
[65]. [Phosphine-Iod2]CTC complexes can red-shift light absorption. Among three CTC
complexes with Iod2 as acceptor, ΔE([2DPP1NA-Iod2]CTC) = 3.29 eV was the highest,
which aligned with its light absorption profile and absorption maxima that its red-
shifted light absorption is the closest to UV range (i.e., the least extent of red-shift)
[65]. Other [phosphine-Iod2]CTC complexes can red-shift light absorption from UV
range to visible light range (blue or green) (e.g., λmax(Iod2) = 277 nm; λmax([DMAPDP-
Iod2]CTC) = 320 nm, 393 nm and 564 nm) due to reduction of HOMO-LUMO gap
(Table 1.9) [65]. Hence, 2DPPBA and DMAPDP were involved in studies of Bis-GMA/
TEGDMA (70%/30%, wt) photopolymerization.

Table 1.9: Summary of HOMO and LUMO energies of phosphines in the absence and the presence
of Iod2 (calculated at the UB3LYP/LANL2DZ Level) [65].

Amines DPPINA DPPBA DMAPDP

HOMO energy (eV) −. −. −.

LUMO energy (eV) −. −. −.
ΔE (eV)  . .
Absorption maxima (nm) ,  ,  , , 

+Iod

HOMO energy (eV) −. −. −.

LUMO energy (eV) −. −. −.
ΔE (eV) . . .
Absorption maxima (nm) , ,  , ,  , , 
1
cationic form

For the photopolymerization of 1.4-mm-thick Bis-GMA/TEGDMA (70%/30%, wt) under

air, with irradiation at 405 nm, photoinitiation ability of [2DPP1NA-Iod2]CTC with low
concentration (donor/acceptor: 0.5%/0.5%, wt) was better than [DMAPDP-Iod2]CTC on
22 D. Zhu et al.

double bond FC (FCt = 100s ([2DPP1NA-Iod2]CTC) = 70%, FCt = 100s ([DMAPDP-Iod2]CTC) =

40%)[65]. Addition of concentration of [donor-acceptor]CTC for [2DPP1NA-Iod2]CTC
prompted a few double bond FCs, while that for [DMAPDP-Iod2]CTC (2%/2%, wt)
increased double bond FCs by ∼40%, similar to FC initiated by [2DPP1NA-Iod2]CTC
(0.5%/0.5%, wt).
Laser-writing experiments using [2DPP1NA-Iod2]CTC and [DMAPDP-Iod2]CTC
with Bis-GMA/TEGDMA were conducted to illustrate the capability of investigated
CTC complexes of 3D printing application. Pattern margin width along cured and
uncured resin board was only 54 μm (similar to the one of the laser beam: ∼50 μm),
which demonstrated that the spatial resolution control of 3D printing using
[2DPP1NA-Iod2]CTC and [DMAPDP-Iod2]CTC were good [65].

Scheme 1.5: Chemical structures of phosphines as donors in CTC systems.

1.1.4 Metal-contained photoinitiators

Metal-contained compound is a large group of visible light PI category [66–69]. For

instance, three metal complexes, zinc tetraphenylporphyrin (ZnTPP), CuC-4 and
Ru, presented in Scheme 1.6, were reported as efficient PIs for FRP and CP. Mean-
while, they were also applied to 3D printing [25, 67, 69].

1.1.4.1 ZnTPP

ZnTPP is a tetraphenylporphyrin complexed with zinc (Scheme 1.6). As depicted in

Table 1.10, ZnTPP can absorb light intensely at 420 nm (λ420 nm = ∼400,000 M−1 cm−1)
and at 552 nm (λ552 nm = ∼200,000 M−1 cm−1) [25]. Light absorption properties of ZnTPP
in combination of photopolymerization of Bis-GMA/TEGDMA and EPOX validated
ZnTPP capability of production of active species when excited by blue and green
lights [25].
For photopolymerization of Bis-GMA/TEGDMA (sample thickness = 1.4 mm), di-
verse visible light LEDs, including LED@405 nm, LED@455 nm, LED@477 nm and
 Chapter 1 Novel photoinitiating systems for 3D printing 23

Scheme 1.6: Chemical structures of introduced metal complexes.

Table 1.10: UV-vis light absorption properties of discussed metal complexes [25].

ZnTPP Ru CuC-A CuC- CuC- CuC- CuC-

λmax (nm)  nm  nm < nm ∼ ∼ ∼ ∼

εmax (M− cm−) , – – – – – –
ε nm (M− cm−) – –   , , ,

LED@530 nm, can excite ZnTPP/Iod (0.3%/1%, wt) to generate free phenyl radicals
and (ZnTPP)•+ under air, which was confirmed via electron paramagnetic resonance
(EPR) experiments, and successfully induce the polymerization [25]. As mentioned
[25], the FC of double bond of methacrylates under air was the highest under irradia-
tion of LED@477 nm after 80 s, among used LEDs (FCC =C, t = 80 s(477 nm) = 70%), while
the lowest upon exposure to LED@405 nm at 100 s (FCC =C, t = 100 s(405 nm) = 12%), as-
cribed to most intense light of LED@477 nm (I477 nm = 300 mW cm−2), leading to fast
polymerization producing cross-linked network, which then protected liquid resin from
the oxygen inhibition effect [25].
The PIS of ZnTPP/Iod (0.3%/1%, wt) presented higher photoinitiation ability in
CP of EPOX (thickness = 25 μm) than FRP of Bis-GMA/TEGDMA under air, upon ex-
posure to blue LEDs in terms of FC (FCepoxy bond, t = 800 s(405 nm) = 47%), while it
was less efficient under irradiation of green light (FCepoxy bond(530 nm) = 33%,
FCC =C(530 nm) = 50%) [25]. Further addition of 0.2 wt% ZnTPP to the PIS (0.3%
ZnTPP/1% Iod, wt) initiated EPOX photocuring under LED@405 nm, improving
FCepoxy bond (405 nm) from 47% to 53% [25]. Moreover, zinc-free ligand (tetraphe-
nylporphyrin (TPP) derivative, H2TPMP), in the presence of Iod, also participated in
photopolymerization of EPOX and presented no polymerization of EPOX under irradi-
ation of LED@405 nm under air [25]. Therefore, metal complexation effect on photo-
initiating capability of TPP has been validated by the comparison of ZnTPP/Iod and
H2TPMP/Iod PISs initiating CP of EPOX.
24 D. Zhu et al.

Due to the higher photoinitiation ability of ZnTPP/Iod in EPOX and oxygen tol-
erance of CP, ZnTPP/Iod (0.3%/1%, wt) in EPOX was included in 3D writing [25].
Numbers (2, 4 and 5) and patterns (rectangular) were successfully formed via 3D
printer projector (λ = 405 nm) [25].

1.1.4.2 Ruthenium complex

Many ruthenium complexes, such as Ru(Ph)32+ and Ru(PPh)32+, have been reported
as efficient PIs over decades [70, 71]. In one report [68], ris(2,2-bipyridyl) dichloror-
uthenium(II) hexahydrate (Ru) was investigated as the PI for gelatin-based bioinks
formation for the cell encapsulation application based on 3D plotted/extruded pro-
tocol, in the presence of sodium persulfate (SPS). Ru was included in the investiga-
tion of 3D printing PI due to the oxygen inhibition effect, compromising formed
hydrogel structure and 3D fidelity seriously [68]. Using Irgacure 2959 under the irra-
diation of UV light (300–400 nm) as the control group, Ru sensitive to visible light
(400–450 nm) was set as the experiment group. A dome and a nose structures were
successfully printed out using the uncured resin of 10 wt% gelatin-methacryloyl
(Gel-MA) with 0.6 wt% collagen [68].
Using PISs and their corresponding irradiation source (30 mW cm−2), the change
of diameter of biofabricated and photopolymerized hydrogel fibers after one day was
only ∼10% for the one initiated by Ru/SPS/visible light (400–450 nm) and was
∼60%–∼70% for the other initiated by Irgacure 2959/UV (300–400 nm). This result
indicated that the formed hydrogel structures photoinitiated by Ru/SPS were more sta-
ble than those initiated by Irgacure 2959, which heavily decomposed within 24 h [68].
As for cell viability studies, the hydrogel formed fiber network initiated by Ru/SPS
under 30 mW cm−2 LED (400–450 nm) encapsulated human articular chondro-
cytes (HAC) or human bone marrow-derived mesenchymal stromal cells (MSC)
ended up with more cell viability after 1-day culture (viabilityHAC(Ru/SPS) = 84%;
viabilityMSC(Ru/SPS) = 86%) than while using Irgacure 2959 under 30 mW cm−2
UV light (300–400 nm) (viabilityHAC(Irgacure 2959) = 76%; viabilityMSC(Irgacure
2959) = 79%) [68]. Furthermore, when using diverse intensities of irradiation sour-
ces (3 mW cm−2, 30 mW cm−2, 50 mW cm−2and 100 mW cm−2), the viability per-
centage of cells encapsulated in formed hydrogel were 85%–90% when using Ru/
SPS under the visible light (400–450 nm) and drastically dropped from 90% to
only ∼45% for Irgacure 2929 under the UV light (300–400 nm), indicating that Ir-
gacure 2959 could generate toxic substances excited by light but Ru/SPS PIS did
not. With the visible light, Ru/SPS is of lower cytoxicity and high cytocompatibil-
ity for application in 3D printing-promoted tissue engineering [68].
 Chapter 1 Novel photoinitiating systems for 3D printing 25

1.1.4.3 Cu(I) complexes

Among the seven Cu-complexes (CuC-1–CuC-7 listed in Scheme 1.7) investigated as

the PIs for 3D printing [67], CuC-4 illustrates light absorption maxima in UV range at
around 350 nm, but it has trace absorption at 405 nm with molar extinction coeffi-
cient of 400 M−1 cm−1 (Table 1.10). CuC-5 has the most red-shifted light absorption
(λmax = ∼450 nm) and CuC-7 has the highest molar extinction coefficient at its ab-
sorption maxima (λmax = ~ 370 nm, εmax = 6,100 M−1 cm−1) [67]. At 405 nm, CuC-5 and
CuC-7 both exhibit higher molar extinction coefficients than CuC-4 (400 M−1 cm−1
refer to Table 1.10). This red-shift trend from CuC-1 to CuC-5 (Table 1.10) could be as-
cribed to the property of substituted group (R) [67].

Scheme 1.7: Chemical structures of investigated Cu complexes.

Even though the light property of CuC-4 was not outstanding, its photoinitiation abi-
lity in CP of EPOX under air and FRP of TMPTA in laminate under irradiation of
LED@405 nm were the best [67]. As for CP of EPOX, two-component PISs (0.5 wt%
PI/1 wt% additive), CuC-4/Iod ended the photopolymerization of EPOX with FCepoxy
bond(CuC-4/Iod) = 48% after only 400-s irradiation (half time for CPs initiated by
other Cu(I)-based PISs), while CuC-5/Iod, CuC-6/Iod and CuC-7/Iod did not induce po-
lymerization of EPOX. CuC-1/Iod and CuC-2/Iod resulted in only ∼6% and ∼12% FC of
epoxy group, respectively, after 800-s irradiation of LED@405 nm under air [67]. The
polymerization of EPOX initiated by CuC-3A/Iod and CuC-3B/Iod completed ∼45%
and ∼63% FC, which were higher than FCepoxy bond(CuC-4/Iod) but took 800 s [67]. As
for FRP, FC of acrylates (i.e., TMPTA) irradiated for 100 s in the presence of Cu(I)/Iod
(0.5%/1%, wt) ranged from 0% (initiated by CuC-5/Iod and CuC-7/Iod) to ∼65% (initi-
ated by CuC-4/Iod); FC of methacrylates, Bis-GMA/TEGDMA, initiated by CuC-4/Iod2
(0.5%/1%) under air for 100-second irradiation was 69% for thick sample (thickness =
1.4 mm) [67]. With the addition of 1 wt% EDB to the CuC-4-based two-component PIS,
CuC-4/Iod2/EDB (0.5%/1%/1%, wt) caused improvement of FC of methacrylates by
11% after 100-s irradiation (FCC =C(CuC4/Iod2/EDB) = 80%) [67].
26 D. Zhu et al.

Concluding the studies of CP and FRP, the three-component PIS, CuC-4/Iod2/

EDB, was considered the best among the investigated Cu(I)-based PISs. Therefore,
CuC-4/Iod2/EDB (0.5%/1%/1%, wt) was chosen as the PIS for printing of patterns
and numbers under LED projector@405 nm, and a few letters, numbers and geo-
metric bars were successfully written using the LED projector@405 nm [67].

1.1.5 Other newly published PIs for 3D printing

Some other reported PISs for 3D printing, such as naphthalimides, acridones, di-
thienophospholes, anthraquinones, etc., are summarized in this section. Besides,
modified commercial PIs can also become more efficient PIs after substitution or
planting onto macromolecules (e.g., BAPO). All presented chemical structures of
the PIs are summarized in Schemes 1.8 and 1.9.

1.1.5.1 Naphthalimide derivatives

Naphthalimide is a synthesized compound containing two benzene rings and an

N-contained-heterocycle. A series of naphthalimide derivatives (amino-/akylamino-/
etc. substituted) were reported as sensitive PIs in the context of UV light to green light
Scheme 1.8 [26]. The NDP2 (Scheme 1.8) chosen as the PI for 3D printing has light ab-
sorption below 475 nm, and its absorption maxima is at 417 nm, with molar extinction
coefficient of 5,600 M−1 cm−1 (Figure 1.7) [26]. In addition, the light absorption of
NDP2 at 405 nm (ε405 nm = 5,100 M−1 cm−1) can ensure its application in 3D printing
[26]. Moreover, EWG (-NO2, NDP1), instead of EDG (-NH2, NDP2), resulted in the
decrease of extinction coefficient in visible light range (ε405 nm(NDP1) = 560 M−1
cm−1; ε405 nm(NDP2) = 5,100 M−1 cm−1), and three other amine-substituted naph-
thalimides, NDP4, NDP6 and NDP7 (chemical structures are not listed), all showed
obvious extinction coefficients at their absorption maxima in visible light range
(λmax = ∼430 nm) [26], in accordance with the results mentioned in the section of
CTC [59].
The photoinitiation abilities of NDP1-7-based PISs for the cationic photopolyme-
rization of EPOX under air and the free radical photopolymerization of TMPTA in
laminate upon the exposure of LED@405 nm were then investigated [26]. The
NDP2/Iod, NDP4/Iod and NDP6/Iod (NDPs: 0.5 wt%, Iod: 2 wt%) can efficiently ini-
tiate polymerization of EPOX upon exposure to LED@405 nm, and three PISs re-
sulted in ∼60% conversion of epoxy group under air after 800-s irradiation while
the conversion of epoxy group for NDP7/Iod was only 28% (Table 1.11). With the
addition of 3 wt% NVK, the FC of EPOX at 800 s was almost not affected, but for
NDP7/Iod/NVK, whose FC increased by 24% (FCEP OX (NDP7/Iod/NVK) = 52%) [26].
For the free radical photopolymerization of TMPTA, adding 3 wt% NVK can improve
Scheme 1.8: Chemical structures of introduced PIs in this section.
Chapter 1 Novel photoinitiating systems for 3D printing
27
28 D. Zhu et al.

FC of TMPTA by 11% to two-component PIS 0.5 wt% NDP2/2 wt% Iod, and by 6%
to 0.5 wt% NDP4/2 wt% Iod (Table 1.11). An interesting finding was that NDP2 can
act as water-soluble PI complexed with cyclodextrin (CD). A blend of HEA/water
(36%/64%, wt) was photoinitiated by NDP2-CD/methyldiethanolamine (MDEA)
PIS and resulted in the final double bond conversion of 80%, under irradiation with
LED@405 nm [26]. Therefore, NDP2 was included in 3D printing due to its versatility in
both 3D printed hydrophilic and hydrophobic polymers [26]. Steady-state photolysis

Scheme 1.9: Chemical structures of modified BAPOs and a commercial PI (Irgacure 2959) as
control.

Figure 1.7: Light absorption maxima and the molar extinction coefficients of PIs in this section.
Solvents used are NDP2, TPA-DTP, 15-DAAQ: acetonitrile; A-2DPA, A-2PTz and BDAPT: toluene
[26, 53 72–77].
 Chapter 1 Novel photoinitiating systems for 3D printing 29

Table 1.11: Photopolymerization of EPOX under air for

800 s and TMPTA in laminate for 400 s upon
exposure to LED@405 nm in the diverse PISs (NDPs:
0.5 wt%, Iod: 2 wt%, NVK: 3 wt%) [26].

FC(EPOX) (%) FC(TMPTA) (%)

Iod Iod/NVK Iod Iod/NVK

NDP    
NDP    
NDP   – –
NDP   – –

Figure 1.8: 3D printed objects using formula containing (A) NDP2/ Iod/NVK (0.5%/2%/3%, wt) in
TEGDA/tricyclodecane dimethanol diacrylate (70%/30%, wt) under air (diameter 4 mm, thickness
2 mm); (B) (1–2) A-2DAP/Iod/NPG (thickness = ∼2,100 µm), (3–4) A-2PTz/Iod/NPG (thickness
= ∼2,220 µm) in the BisGMA/TEGDMA (0.00625% Acridone/0.125% Iod/0.125% NPG, wt); (C1) 15-
DAAQ/TEAOH/R-Br (0.5%/2%/2%, wt) (64.0 mm * 30.0 mm * 3.6 mm), (C2) 15-DAAQ/Iod/TMA/
MWCNT (0.5%/2.0%/2.0%/0.5%); (D) SFH+/TPB/TA (0.4%/1%/1%, wt) in SR349; (E) 0,1 wt% yellow
triazine in DPGDA (32 mm * 32 mm * 18 mm); (F) OCE3-2; (G) HAPI, the object was encapsulated with
MC3T3 [26, 34, 53, 73, 76–79]. Adapted with permission from [26, 34, 53, 73, 76–79]. Copyright 2015
American Chemical Society, Copyright 2019 American Chemical Society, Copyright 2019 Wiley‐VCH
Verlag GmbH & Co. KGaA, Weinheim, Copyright 2019 WILEY‐VCH Verlag GmbH & Co. KGaA,
Weinheim, Copyright 2018 Elsevier Ltd., Copyright 2017 The Royal Society of Chemistry, Copyroght
2019 Wiley‐VCH Verlag GmbH & Co. KGaA, Weinheim and Copyright 2018 American Chemical Society.

results demonstrated that the light absorption profile dropped significantly within
only 10 s, indicating its quick photobleaching property and the efficient interac-
tion between NDP2 and Iod [26]. To validate whether investigated NDPs can be
used in 3D printing, a 4-mm-diameter, 2-mm-thick polymer disk was successfully
cured using triethylene glycol diacrylate/tricyclodecane dimethanol diacrylate
(70%/30% w/w) under LED projector under air within 30 s (Figure 1.8(A)). This
30 D. Zhu et al.

positive result determined that NDP2/Iod/NVK is an outstanding PIS for 3D

printing.

1.1.5.2 Acridone derivatives

Acridone derivative-based PISs, A-2DPA and A-2PTz (Scheme 1.8) in the presence of
Iod2 (Scheme 1.4) were investigated as efficient PISs for 3D printing [61]. As presented
in Figure 1.7, green dot (A-2DPA) and blue dot (A-2PTz) are placed at up left side,
which demonstrates that they have intense light absorption in short wavelength rage
less than 380 nm (λmax(A-2DPA) = 354 nm and λmax(A-2PTz) = 313 nm). Corresponding
molecular extinction coefficients at their absorption maxima are εmax(A-2DPA) =
33,400 M−1 cm−1 and εmax(A-2PTz) = 18,200 M−1 cm−1 [61]. Meanwhile, they both have
profile tails in visible light range from 400 nm to 470 nm (ε405 nm(A-2DPA) = 2,500
M−1 cm−1 and ε405 nm(A-2PTz) = 3,600 M−1 cm−1) [61]. As for A-2DPA, it also absorbs
green light (extinction coefficient at 510 nm: ε510 nm (A-2DPA) = ∼2,000 M−1 cm−1) [61].
The photoinitiation ability of A-2DPA and A-2PTz in two- or three-component
PISs in the presence of Iod2 and/or EDB (or NPG) were determined by photopolyme-
rization studies of EPOX (thickness = 25 μm) under air, TMPTA (thickness = 25 μm)
in laminate and Bis-GMA/TEGDMA (70%/30%, wt) (thickness = 1.4 mm) under air
[61]. For the CP of EPOX, A-2PTz/Iod2 was of higher efficiency than A-2DPA/Iod2 in
the CP of EPOX. The FC of epoxy group that resulted from A-2DPA/Iod2 (0.1%/1%,
wt) was negligible, while that initiated by A-2PTz/Iod2 (0.1%/1%, wt) was 45% [61].
Addition of extra 0.2 wt% acridone improved efficiency of acridone-based PISs in
terms of FCepoxy group (FCepoxy group, t = 800 s(A-2PTz/Iod2) = 47%; FCepoxy group, t = 800 s
(A-2DPA/Iod2) = 62%) [61]. For FRP of TMPTA, two-component PISs, A-2PTz/Iod2
(0.05%/1%, wt) gave a good result that FC of double bonds of TMPTA was 55%
under air (thickness = 1.4 mm), while there was no polymerization for A-2DPA/Iod2
(0.05%/1%, wt) [61]. The three-component PISs in the presence of Iod and NPG
showed outstanding results that FCs of acrylates double bonds were 85% for A-
2DPA/Iod2/NPG and 84% for A-2PTz/Iod2/NPG [61]. This should be ascribed to the
mentioned CTC combination, and [NPG-Iod2]CTC has superb photoinitiating and
thermal-initiating ability [59, 65]. Although the [NPG-Iod2]CTC resulted in an out-
standing FC of double bond of TMPTA, the addition of A-2DPA and 2-PTz did accel-
erate the rate of TMPTA polymerization [61]. For 150-s irradiation-initiated FRP of
viscous resin, methacrylates (Bis-GMA/TEGDMA), the concentration of acridone led
to negative effects on polymerization [61]. For both A-2DPA- and A-2PTz-based two-
component PISs (in the presence of 1 wt% Iod2), 0.05 wt% acridone-based PISs re-
sulted in 66% methacrylates polymerized; however, only 63% or 62% methacrylates
polymerized with the addition of extra 0.05 wt% acridone [61]. Furthermore,
0.3 wt% and 0.5 wt% acridone/Iod2 PISs cannot initiate the polymerization of Bis-
GMA/TEGDMA [61]. Acridone/NPG or acridone/EDB (0.5%/1%, wt) also gave rise
 Chapter 1 Novel photoinitiating systems for 3D printing 31

to no polymerization of Bis-GMA/TEGDMA [61]. The three-component PISs, acri-

done/Iod2/NPG (0.05%/1%/1%, wt), were more efficient than the two-component
PISs (FCt = 150 s(A-2PTz/Iod2/NPG) = 82%; FCt = 150 s(A-2DPA/Iod2/NPG) = 81%) [61].
Low PI migration property was also validated via UV-vis quantifying PI partitioning
into acetonitrile by soaking, and the results demonstrated that only 1.9% A-2DPA and
A-2PTz were migrated [61]. With acridone/Iod2/NPG (0.00625%/0.125%/0.125%, wt) in
Bis-GMA/TEGDMA, ∼2,100 μm thick sample, “DPA” (Figure 1.8(B1, B2), for A-2DPA)
and ∼2,220 μm thick sample, “PTz” (Figure 1.8(B3, B4)), for A-2PTz were successfully
laser-written within 1 min [61].

1.1.5.3 Dithienophosphole derivatives

Dithienophospholes (DTP) substituted with and without N,N-phenylamine (-NPh2)

(TPA-DTP and Ph-DTP in Scheme 1.8) are presented in this section. Compared to the
commercial PI, BAPO (λmax (BAPO) < 400 nm, εmax (BAPO) < 5,000 M−1 cm−1), TPA-
DTP (λmax (TPA-DTP = 465 nm)) and Ph-DTP (λmax(Ph-DTP) = 420 nm, Figure 1.7) can
absorb light in visible range. Obviously, with -NPh2 substitution, TPA-DTP presented
more red-shift light absorption than Ph-DTP [74]. At 405 nm, which is the common
wavelength for 3D printer projector, TPA-DTP absorbs more photons than Ph-DTP
(ε405 nm (TPA-DTP) = ∼12,800 M−1 cm−1, ε405 nm (Ph-DTP) = ∼12,000 M−1 cm−1). More-
over, Ph-DTP and TPA-DTP both presented higher extinction coefficients at 405 nm
than BAPO (ε405 nm (BAPO) = ∼500 M−1 cm−1) [74].
Photoinitiation abilities of TPA-DTP and Ph-DTP were investigated via photopoly-
merization of EPOX, TMPTA and Bis-GMA/TEGDMA [74]. As for CP of EPOX initiated
by the two-component PISs (0.5 wt% PI/1 wt% Iod), DTPs-based PISs exhibited better
photoinitiation abilities compared to BAPO-based PIS (FCepoxy(TPA-DTP/Iod) = 53%;
FCepoxy(Ph-DTP/Iod) = 41%; FCepoxy (BAPO/Iod) = 15%), illustrating that amine substi-
tuted DTP (TPA-DTP) not only presented light absorption in longer wavelengths but
also resulted in more EPOX polymerized [74]. As to FRP of TMPTA, the photoinitiation
ability of TPA-DTP-based PIS in terms of double bond FC of TMPTA was also better
than Ph-DTP/Iod (FCC=C(TPA-DTP/Iod) = 47%, FCC=C(Ph-DTP/Iod) = 41%) for the sam-
ple in laminate, under irradiation for 100 s (thickness = 25 μm) in the presence of 1 wt
% Iod [74]. According to study of TMPTA, the effect of DTP concentration on photo-
polymerization was surprisingly negative in the thick sample (thickness = 1.4 mm)
with DTP/1 wt% Iod under air for 100 s irradiated by LED@405 nm [74]. With TPA-
DTP concentration reduction from 0.5 wt% to 0.001 wt% in gradient, the FCC=C drasti-
cally increased from 5% to 30%, which might be ascribed to its deep red color that
could reduce light throughput for PI excitation [74]. The photopolymerization of
Bis-GMA/TEGDMA processed in the presence of 0.01 wt% TPA-DTP/1 wt% Iod
under air upon exposure to LED@405 nm was of higher FC of C=C (FCC=C(Bis-GMA
/TEGDMA) = 54%) than the photopolymerization of TMPTA, under the same
32 D. Zhu et al.

conditions (FCC=C (TMPTA) = 30%) due to their different viscosity [40, 74]. However,
EDB, instead of Iod, that participated in two-component PISs led to no polymeriza-
tion of Bis-GMA/TEGDMA [74]. With the most efficient PIS (TPA-DTP/Iod: 0.001%/
1%, wt) validated by CP and FRP studies in the context of various conditions, the 2-
mm thick logo “CNRS” was successfully written by laser using Bis-GMA/TEGDMA as
monomer in a short irradiation time (<1 min) [74].

1.1.5.4 Diaminoanthraquinones

Anthraquinone derivatives such as hydroxy-substituted, and amino-substituted an-

thraquinones [30–32, 35, 36] are popular objects in PI exploration. Among these,
a diamino-substituted anthraquinone (DAAQ), 15-DAAQ (Scheme 1.8), has been
proved to be a highly efficient PI for 3D printing [34, 80]. As reported [34, 80], 15-DAAQ
has its light absorption maxima at 479 nm (εmax = 9,300 M−1 cm−1) [34, 75, 80]. In the
report [80], the projector of the 3D printer emitted from 400 nm to 750 nm, which
overlaps with the 15-DAAQ light absorption profile. The photoinitiation abilities of
15-DAAQ in the presence of diverse additives were investigated upon exposure to
LED@455 nm (blue), LED@518 nm (green), LED@594 nm (yellow) and LED@636 nm
(red). To find out optimal additives for DAAQ-based PIS that had lower cost and
higher efficiency than Iod and NVK, triethanolamine (TEAOH) and phenacyl bromide
(R-Br) were considered as alternatives [80]. From the results of steady state photoly-
sis experiments and fluorescence spectra, it has been confirmed that 15-DAAQ/
TEAOH and 15-DAAQ/R-Br had interaction under irradiation of LED@518 nm [80].
For 15-DAAQ/TEAOH, it produced intermediates having less light absorption at
480 nm and more absorption at ∼580 nm [80].
To reveal the photoinitiation ability of DAAQ-based PISs in 3D printing appli-
cations, the commercial resin for 3D printing in the absence of commercial PIS
was mixed with 15-DAAQ in the presence of TEAOH and/or R-Br. As concluded in
Table 1.12, two-component 15-DAAQ-based PISs (with TEAOH or R-Br) presented
lower initiation capability of 3D resin curing than three-component 15-DAAQ-based
PISs, in terms of FC. As for three-component 15-DAAQ-based PISs, 15-DAAQ/Iod/NVK
and 15-DAAQ/TEAOH/R-Br were investigated under the four above mentioned LEDs
(Table 1.12). Irradiated by LED@455 nm (60 mW cm−2) or LED@518 nm (60 mW cm−2),
three-component 15-DAAQ/TEAOH/R-Br PISs overweighed 15-DAAQ/Iod/NVK in terms
of FC of double bond by 5%–8% (Table 1.12) [80]. Therefore, 15-DAAQ/TEAOH/R-Br
(0.5%/2%/2%, wt) was then applied to 3D keyring printing (Figure 1.8(C1)) [80].
In another report [34], EDB, 4-(dimethylamino)benzaldehyde (DMAB), N,N-
dimethylaniline (DMA) and 4,N,N-trimethylaniline (TMA) were also involved in an
investigation of additives for 15-DAAQ-based PISs under LED@518 nm irradiation.
According to photopolymerization of PEGDA MW250 studies, 15-DAAQ/Iod/TMA
and 15-DAAQ/Iod/DMA (0.023 M/0.052 M/0.164 M) presented an outstanding FC of
 Chapter 1 Novel photoinitiating systems for 3D printing 33

Table 1.12: Photopolymerization of Monocure 3D resin (without commercial PI) in laminate upon
exposure to various LEDs for 300 s, in the presence of 15-DAAQ and diverse additives (15-DAAQ:
0.5 w%; Iod, TEAOH, and R-Br: 2 wt%; NVK: 3 wt%) [34, 79].

Additives  nm  nm  nm  nm

Iod/NVK % % np *

np*
TEAOH % % np* np*
R-Br % % np* np*
TEAOH/R-Br % % np* np*
*
np: no polymerization

double bond (∼80%) among all two-component and other three-component 15-
DAAQ-based PISs [34]. 1.5-DAAQ/Iod/TMA (0.5%/2%/2%, wt) PIS then successfully
initiated 3D printing of some logo pads [34]. To expand the application of 15-DAAQ-
based PISs in 3D printing resin, fillers, multiwall carbon nanotube (MWCNT), were
added into the uncured formula for 3D printed object reinforcement [34]. The photo-
polymerization of PEGDA MW250 showed that the filler less than 10 wt% did not
attenuate the photoinitiation ability of 15-DAAQ/Iod/TMA PIS, ascribed to its lim-
ited effect on light penetration [34]. Therefore, a tower (Figure 1.8(C2)) of dimen-
sions 10.9 mm × 10.9 mm × 4.7 mm was printed in the presence of 0.5 wt% MWCNT,
which allowed for further stereoscopic objects printing, rather than only the planar
objects.

1.1.5.5 Safranine O

Safranine O (SFH+) is a phenazine derivative (Scheme 1.8). The impressive three-

component PIS based on SFH+ has turned out to be efficient for 3D printing, that
tetrabutylammonium tetraphenylborate (TPB) and triazine A (R-Cl) were used as co-
initiator and redox, respectively [78]. Photopolymerization of acrylates, ethoxylated
(3) bisphenol A diacrylate (SR349), in solvent, propylene carbonate (PC), was per-
formed to illustrate photoinitiating ability of SFH+ [78]. The two-component SFH+-
based PISs consisting of TPB or R-Cl, gave rise to double bond conversion of SR349
less than 10%, while the three-component SFH+-based PIS containing both TPB and R-
Cl presented the most efficient photoinitiation ability with FCC =C = 57.3% and RP,max =
7.2 s−1 (SFH+: 0.1 wt%, TPB: 1 wt%, R-Cl: 1 wt%, LED@532 nm, in laminate) [78].
Light penetration and cure depth studies were performed to confirm the most op-
timal component ratio. According to the results, increasing irradiance reduced inhibi-
tion time and critical time drastically, within weak irradiance range. The irradiance
did not affect light penetration depth (DP) but SFH+ concentration did (DP (0.05 wt%)
= 220 µm, DP (0.1 wt%) = 170 µm, DP (0.2 wt%) = 100 µm and DP (0.4 wt%) = 60 µm)
[78]. Since the model layer thickness was set as 50 µm, the formula composed of
34 D. Zhu et al.

SFH+/TPB/R-CL (0.4%/1%/1%, wt) and SR349 was prepared for 3D printing, guaran-
teeing enough DP and fast RP. A sharp Eiffel Tower with high resolution was effectu-
ally printed out by a B9Creator DLP 3D printer (Figure 1.8(D)) [78].

1.1.5.6 Yellow Triazine

R-Cl (Scheme 1.8), indicated as additive in SFH+-based PIS [78], was determined to be
an efficient type I and type II PI in CP and FRP [81, 82]. In the report [73], R-Cl was
efficient in 3D printing applications. The light absorption maxima of R-Cl is at 373 nm
and the corresponding molar extinction coefficient is 44,000 M−1 cm−1 (Figure 1.7),
and it also exhibits light absorption at 405 nm (ε405 nm = 17,000 M−1 cm−1) [82]. Be-
sides, upon exposure to LED@405 nm (∼110 mW cm−2), it has been confirmed that
R-Cl can initiate FPR of TMPTA under air with the FC = 25% under irradiation of
LED405 nm [82].
To optimize the 3D printing resin composites for R-Cl-based PIS, various acryl-
ates were considered as potential monomers/oligomers for optimized fast 3D
printing. The acrylates used included tetra(ethylene glycol) diacrylate (TetEGDA),
poly(ethylene glycol) diacrylate Mn = 575 (PEGDA575), poly(ethylene glycol) diacry-
late Mn = 700 (PEGDA700), 1,6-hexanediol diacrylate (HDDA), di(ethylene glycol) dia-
crylate (DEGDA), di(propylene glycol) diacrylate (DPGDA) and tri(propylene glycol)
diacrylate (TPGDA), EBECRYL® 605 (EB605; it is the bisphenol A epoxy diacrylate,
EBECRYL® 600, diluted 25 wt% with TPGDA) and Bis-GMA/TEGDMA [73]. All acryl-
ates mentioned can be initiated by R-Cl (FCsC =C > 50%) [73]. TetEGDA, DEGDA and
DPGDA, in the presence of 0.5 wt% R-Cl, were the three systems that were more effi-
cient than other monomers in terms of rate of polymerization (RP max), that RP,max
(TetEGDA) = 14.84 s−1, RP,max(DEGDA) = 13.82 s−1 and RP, max(DPGDA) = 13.21 s−1 [73].
And PEGDA575, PEGDA700 and TetEGDA can be initiated by R-Cl to lead to high
double bond conversions under the irradiation of the LED@400 nm (∼4 mW cm−2),
with the emission wavelength and intensity similar to those of the used 3D
printer projector, that FCC =C(PEGDA575) = 91%, FCC =C(PEGDA700) = 91% and FCC =C
(TetEGDA) = 88% [73].
As TetEGDA was of both high RP,max and FC, photoinitiated by R-Cl under the
LED similar to 3D printer projector, it was set as model monomer for further PI con-
centration optimization. As the result of similar FCsC =C of TetEGDA initiated by
0.1 wt%, 0.3 wt% and 0.5 wt% R-Cl, the concentration of R-Cl was little affected
when it was higher than 0.1 wt%. Specifically, threefold and fivefold 0.1 wt% R-Cl
concentration only improved FC of TetEGDA by 6% and 11% (i.e., FCC =C(0.1 wt%) =
77%, FCC =C(0.3 wt%) = 83% and FCC =C(0.5 wt%) = 88%) [73].
Even though 0.1 wt% R-Cl was superb for photopolymerization of TetEGDA, re-
duction of PI concentration could decrease potential risk of PI migration due to less
concentration in resin. As 0.05 wt% R-Cl in TetEGDA resulted in FCC =C = 65% and
 Chapter 1 Novel photoinitiating systems for 3D printing 35

RP,max = 7.67 s−1, which was acceptable for 3D printing [73], 0.1 wt% and 0.05 wt%
R-Cl mixed with TetEGDA were prepared for 3D printing of a pyramid (32 mm ×
32 mm × 18 mm) (0.05 wt% R-Cl: Figure 1.8(E)) [73]. Clearly, the resolution of the
pyramid using 0.1 wt% R-Cl was higher than the one using 0.05 wt%, due to faster
RP,max of the more concentrated R-Cl. The same condition and process was also fol-
lowed for a commercial PI, BAPO, to 3D print the pyramid, but the stairs printed
was blurred [73]. R-Cl was turned out to be an efficient PI for 3D printing.

1.1.5.7 Modified BAPOs

TPO and BAPO are well-known and efficient commercial PIs [4]. Improvement of their
properties (e.g., solubility) and reduction of their drawbacks (e.g., PI migration) are
alternatives for discovery of novel PISs. Two main methods are the synthesis of their
derivatives and bonding them onto a carrier (e.g., cellulose nanocomposite (CNCs),
PEG, etc.). Examples of modified BAPOs are presented in this section (Scheme 1.9)
[83, 84]. For easy comparison, some commercial PIs (e.g., Irgacure 2959, BAPO-Ona
and BAPO-OLi) were used as one-component PISs in control group [83, 84].
Bonding phosphine-atom in BAPO structure onto PEG (Scheme 1.9) can enhance
the PI homogeneous dispersity in water phase due to hydrophilicity of PEG (i.e., 3 g
PEG-BAPO in 7 mL water) [83]. Furthermore, PEG-BAPO exhibits light absorption at
405 nm with higher molecular extinction coefficient in UV and blue light range (λ <
440 nm) than the mentioned BAPO derivatives (BAPO-OLi and BAPO-ONa) and Irga-
cure 2959 (Figure 1.9) [83]. With promoted light absorption property in blue light

800
PEG-BAPO
Molar extinction coefficient (M–1 cm–1)

BAPO-OLi
BAPO-ONa
600 Irgacure 2959

400

200

0
320 340 360 380 400 420 440 460
Wavelength (nm)

Figure 1.9: UV-vis absorption spectra of PEG-BAPO and commercial PIs in water (PI: 1 mM) [83].
Reproduced with permission from [83]. Copyright 2018 The Royal Society of Chemistry.
36 D. Zhu et al.

range and water solubility, the photoinitiation ability of PED-BAPO was then investi-
gated in aqueous media [83]. The photoinitiation ability comparison among PEG-
BAPO and BAPO derivatives (BAPO-OLi and BAPO-ONa) in 50 wt% aqueous solution
of poly(ethylene glycol) diacrylate (PEGDA Mn700) was determined via photorheome-
ter (Figure 1.10). In accordance with the photo-DSC results, even though the FCC =C of
PEGDA Mn700 were almost similar among the three PIs (FCC =C(PEG-BAPO) = 55%,
FCC =C(BAPO-ONa) = 52% and FCC =C(BAPO-OLi) = 56%), PEG-BAPO resulted in the
shortest delay time (td = 12.1 s) (Figure 1.10(b)) and the highest rate of polymerization
determined by ΔG′/Δt = 23.1 KPa/s (Figure 1.10(c)). The time taken to reach 95% of the
total polymerization enthalpy (t95%) initiated by PEG-BAPO was t95%(PEG-BAPO) = 53 s
while t95%(BAPO-ONa) = 76 s, t95%(BAPO-OLi) = 70 s, which validated the high photo-
initiation ability of PEG-BAPO.
Besides PEG, cellulose nanocrystal-carrying BAPO is also reported as efficient
PIS for hydrogel 3D printing [84]. BAPO-ONa (Scheme 1.9) in the absence and the

(a) 600

500

400
G’max [kPa]

300 Light off

200

100 PEG-BAPO
BAPO-OLi
BAPO-ONa
0
0 50 100 150 200 250 300
Time (s)

Time (s)
(b) 70 (c)
58.8 25 23.1
60

50 20
40.3
slope [kPa/s]

40 15
td [s]

30
10 8.3
7.2
20
12.1
5
10

0 0
PEG-BAPO BAPO-OLi BAPO-ONa PEG-BAPO BAPO-OLi BAPO-ONa

Figure 1.10: Photo-rheology measurements of PEGDA Mn700 in the presence of PEG-BAPO,

BAPO-OLi or BAPO-ONa (PI: 5 mM). (a) Photo-rheometer curves. The light was automatically turned
on after 120 s. (b) Delay time (td) of the three different PIs. (c) Slope ΔG′/Δt of the three different
PIs [83]. Reproduced with permission from [83]. Copyright 2018 The Royal Society of Chemistry.
 Chapter 1 Novel photoinitiating systems for 3D printing 37

presence of freely neat CNC as PISs in monofunctional methacrylate, PEGMEM, pre-

sented similar but low gel content percentage (16% and 22%, respectively) and
Young’s modulus (130 ± 38 MPa and 272 ± 20 MPa, respectively) [84]. On the contrary,
valent-linked CNC-BAPO (3.27 wt%) having the same amount of BAPO as the PIS of
BAPO, in the presence of CNC, resulted in around fourfold gel content percentage in
PEGMEM resin (82%) with cross-linking density of 0.006 mmol cm−3 [84].
Furthermore, increasing CNC-BAPO concentration (6.14 wt%) did not affect gel
content but increased Young’s modulus to 340 ± 25 MPa and cross-linking density
to 0.028 mmol cm−3, which correspondingly decreased swelling ratio from 1,100 ±
65% (3.27 wt% CNC-BAPO) to 740 ± 40% (6.14 wt% CNC-BAPO) [84]. Hence, the
CNC-BAPO was chosen as PIS for 3D printing.
3D printed gyroid structure using PEG-BAPO and cubic and beehive structures
using CNC-BAPO are presented in Figure 1.11. In Figure 1.11A(a), a coin-sized inner-
vortex object was scanned under microscopy. The precision of x-y lateral dimensions
were well-constructed (Figure 1.11A(b)) while the z-deviation appeared by 342 nm
(Figure 1.11A(c)). As for CNC-BAPO, the printed hydrogel (Figure 1.11B(a)) can hold
100 g weight on dried object and 20 g weight on swollen object (Figure 1.11B(b–d)).

A: PEG-BAPO B: CNC-BAPO
(a) (a) (b)
Swollen

Dried 100 g

(c) (d)
20 g

(b)

(e) (f)

(c)

1 cm 1 cm

Figure 1.11: 3D printed hydrogels using (A): PEG-BAPO in 50 wt% PEGDA Mn700 using 460 nm
irradiation and (B): CNC-BAPO as photoinitiators in 50 wt% PEGMEM under 405 nm LED [83, 84].
Adapted with permission from [83, 84]. Copyright 2018 The Royal Society of Chemistry and
Copyright 2018 Wiley‐VCH Verlag GmbH & Co. KGaA, Weinheim.
38 D. Zhu et al.

In Figure 1.11B(e,f), (b–f), the blue CNC-BAPO inside can be removed by rinsing the
beehive structure in water and then drying, along with CNC-BAPO partitioning activity.
With results of PEG-BAPO and CNC-BAPO, planting of BAPO onto macrostructure
could be considered for development of novel PI/PIS with high migration stability.

1.1.5.8 Semiconductor-metal hybrid nanoparticle

A hybrid nanoparticle (HNP) was discovered as a “photoinitiator” recently [85]. As

illustrated in Figure 1.12(a, b), the photon (hν) emits onto gold-tipped cadmium sul-
fide nanorods, and the excited gold can produce electrons interacting with water
and/or oxygen to form active species (free radicals) that can initiate polymerization
(Figure 1.12(a, b)). The photopolymerization of acrylamide in water upon exposure
to LED@385 nm was performed for the investigation of its photoinitiation ability
[85]. It was found that the FC of acrylamide increased along with increasing HNP
concentration (FCC =C(0.1 μM) = 0%, FCC =C(0.2 μM) = ∼20%, FCC =C(0.3 μM) = ∼60%,
FCC =C(0.45 μM) = ∼90%, FCC =C(1.8 μM) = ∼100%) [85]. Moreover, the effect of vari-
ous solvents on the polymerization performance was studied. It demonstrated that
water was the best media enabling 70% acrylamide polymerization, while the FC of
polymerization conducted in ethanol was only ∼25% due to ethanol’s role as radical
scavenger [85]. For 3D printing, 0.4 μM CdS-Au HNP was used as photoinitiator,
and a 3D printed spherical hydrogel objective (Figure 1.12(c)) was successfully
formed, when a 3D printer was used with the projector at 385 nm (17.5 mW cm−2)
More interestingly, the giant two-photon absorption cross section ∼107 GM of
HNP can allow it to achieve nanolithographic writing [85]. To validate this hypothe-
sis, a nanospiral structure (120 × 120 × 16 μm) has been printed by a two-photon
printer [85]. Metal nanoparticle is an interesting concept in photopolymerization
and 3D printing. An extra step between being irradiated and generating active spe-
cies is electron production, which differs from traditional PIs [85]. This should be a
promising and attractive research area, in future.

1.1.5.9 Photoinitiators for two-photon nanolithography

Two-photon nanolithography has been mentioned in the previous sections (e.g.,

CNC-BAPO, carbazole-oxime-esters). More two-photon PIs are concluded here as
they are validated for only two-photon nanolithography, even though they might
be promising in centimeter-scale 3D printing. Two-photon printing shows potential
in nanoscale and precise applications such as cell encapsulation, tissue engineer-
ing and drug delivery [77, 86]. More details on the progress of the newly developed
two-photon initiators in recent years are presented in Chapter 2. The functional 3D
nanoprinting technique via two-photon lithography is demonstrated in Chapter 8.
Figure 1.12: Mechanism of polymerization photoinitiated by HNP [85]. Adapted with permission from [85]. Copyright 2017 American Chemical Society.
Chapter 1 Novel photoinitiating systems for 3D printing
39
40 D. Zhu et al.

Oxime-esters
As mentioned in the section on carbazole derivatives, the carbazole-oxime-esters
have capability of TPP and formation of micro fabricated structure. Other oxime-
ester derivatives, OEC3-2 and BDAPT (Scheme 1.8), have been reported as two-
photon-initiators (TPI), as well [53, 72]. As a two-photon absorption chromophore
core of the OEC3-2 and BDAPT, coumarin structure and thioxanthone structure
were conjunct with one or two oxime-ester groups responsible for initiation [53, 72].
According to Figure 1.7 and Table 1.13, OEC3-2 has light absorption below 500 nm
and absorption maxima at 466 nm with extinction coefficient at its absorption max-
ima of 35,000 M−1 cm−1; BDAPT absorbs maximum light at 408 nm (dissolved in
toluene) with εmax(BDAPT) = 9,100 M−1 cm−1. As half wavelength of diode laser writ-
ing should be the wavelength at which the compound has light absorption, OEC3-2
and BDAPT are supposed to be sensitive to 800-nm infrared [72].

Table 1.13: One-photon and two-photon properties of

OEC3-2, BDAPT and HAPI [77].

λmax(nm) εmax(M− cm−) σPA (GM)

OEC-  , a

BDAPT  , b
HAPI  , a

Two-photon cross sections at a: 800 nm, b: 788 nm

To investigate the TPI ability of OEC3-2 and BDAPT, σ2PA, 800 nm was obtained from
z-scan (σ2PA, 800 nm(OEC3-2) = 536 GM, σ2PA, 788 nm(BDAPT) = 368 GM) (Table 1.13),
which was higher than many of published two-photon initiators such as the men-
tioned carbazole-oxime-ester, 4d (σ2PA, 800 nm(4d) = 136 GM) [52, 53]. The laser
power window for two-photon initiated nanolithography of high resolution and
quality was 10 mW–28 mW, which is similar to the laser power window of 4d
(8 mW–30 mW) [52, 53]. The same structure as that in Figure 1.8(F) was successfully
printed out, using a formula comprising of OEC3-2 as initiator, and some nanoscale
polymer lines was formed, using 100 µm s−1 with the 800 nm diode laser [52, 53].
Nanoscale lines were written by 800-nm laser using BDAPT, as well [72].

Macro photoinitiator
HAPI, a macro photoinitiator substituted with MGABA (Scheme 1.8), has light ab-
sorption below 600 nm and maximum one-photon light absorption at 466 nm with
εmax = 35,000 M−1 cm−1 (Figure 1.7 and Table 1.13); thus, it is a promising TPI under
800 nm [77]. The two-photon absorption spectra of HAPI validated its capability of
being a TPI [77]. The two-photon absorption cross section of HAPI was 400 GM
(Table 1.13), which is higher than BDAPT but lower than OEC3-2. A mixture of 15%
 Chapter 1 Novel photoinitiating systems for 3D printing 41

GelMod, 1 mM HAPI and 10 mM MBCD in αMEM cell culture medium containing

MC3T3 cells was prepared for two-photon 3D printing (Figure 1.8(G)) [77]. A yin-
yang structure was formed in the cell culture medium. The cell stayed alive for
5 days after yin-yang structure formed and continued to proliferate.
Extra studies including transmembrane migration and cytotoxicity were con-
ducted for safety concerns applied to tissue engineering. Exciting results that HAPI
was prevented from entering cell membrane by covalent of hyaluronan, and negligible
cytotoxicity was found in HAPI contained assay [77] came out. Macro-, hydrophilic-
and two-photon PIs are hence promising in pharmaceuticals.

1.1.6 Conclusions and perspectives

In this chapter, various categories of PIs (e.g., natural derivatives, metal complexes,
CTC, etc.) were presented for their potential in 3D printing. The PISs of efficiency
under light from UV to red were introduced. PIS for centimeter-scale 3D printing
and microscale 3D printing were described as well. Key properties of PI and/or PIS
that need to be considered were enclosed (e.g., UV-vis absorption, fluorescence,
two-photon absorption cross section, etc.). To expand the scope of PIs, the follow-
ing approaches are supposed to be firstly considered:
– naturally derived compounds discovery
– molecule modification by substitution
– photosensitive molecule conjugated with macromolecule

Although drawbacks of commercial PIs (e.g., UV-irradiated, PI migration, unstable)

are overcome by newly reported PIs, further investigation is necessary to improve
their efficiency. A PI with diverse advantages (e.g., low/no PI migration, nontoxic,
active to low intensity visible light and hydrophilic), all in one, is anticipated in
future.

References
[1] Bowman, C. N., Kloxin, C. J. Toward an enhanced understanding and implementation of
photopolymerization reactions, AIChE J, 2008, 54(11), 2775–2795.
[2] Bagheri, A., Jin, J. Photopolymerization in 3D Printing, ACS Appl Polym Mat, 2019, 1(4),
593–611. 10.1021/acsapm.8b00165.
[3] Yagci, Y., Jockusch, S., Turro, N. J. Photoinitiated polymerization: Advances, challenges, and
opportunities, Macromolecules, 2010, 43(15), 6245–6260. 10.1021/ma1007545.
[4] Zhang, J., Xiao, P. 3D printing of photopolymers, Polym Chem, 2018, 9, 1530–1540.
[5] PHARMACEUTICALS U.S. Food & drug administration approves first 3-D printed drug, Chem
Eng News Arch, 2015, 93(32), 7. 10.1021/cen-09332-notw7.
42 D. Zhu et al.

[6] Bozuyuk, U., Yasa, O., Yasa, I. C., Ceylan, H., Kizilel, S., Sitti, M. Light-Triggered drug release
from 3D-Printed magnetic chitosan microswimmers, ACS Nano, 2018, 12(9), 9617–9625.
10.1021/acsnano.8b05997.
[7] Credi, C., Fiorese, A., Tironi, M., Bernasconi, R., Magagnin, L., Levi, M., Turri, S. 3D printing of
cantilever-type microstructures by stereolithography of ferromagnetic photopolymers, ACS
Appl Mater Interfaces, 2016, 8(39), 26332–26342. 10.1021/acsami.6b08880.
[8] Dickerson, M. B., Dennis, P. B., Tondiglia, V. P., Nadeau, L. J., Singh, K. M., Drummy, L. F.,
Partlow, B. P., Brown, D. P., Omenetto, F. G., Kaplan, D. L., Naik, R. R. 3D printing of
regenerated silk fibroin and antibody-containing microstructures via multiphoton
lithography, ACS Biomat Sci Eng, 2017, 3(9), 2064–2075. 10.1021/acsbiomaterials.7b00338.
[9] Herzberger, J., Meenakshisundaram, V., Williams, C. B., Long, T. E. 3D printing all-aromatic
polyimides using stereolithographic 3d printing of polyamic acid salts, ACS Macro Lett, 2018,
7(4), 493–497. 10.1021/acsmacrolett.8b00126.
[10] Kuang, X., Chen, K., Dunn, C. K., Wu, J., Li, V. C. F., Qi, H. J. 3D printing of highly stretchable,
shape-memory, and self-healing elastomer toward novel 4D printing, ACS Appl Mater
Interfaces, 2018, 10(8), 7381–7388. 10.1021/acsami.7b18265.
[11] Manzano, J. S., Weinstein, Z. B., Sadow, A. D., Slowing, I. I. Direct 3D printing of catalytically
active structures, ACS Catal, 2017, 7(11), 7567–7577. 10.1021/acscatal.7b02111.
[12] Palaganas, N. B., Mangadlao, J. D., de Leon, A. C. C., Palaganas, J. O., Pangilinan, K. D., Lee,
Y. J., Advincula, R. C. 3D printing of photocurable cellulose nanocrystal composite for
fabrication of complex architectures via stereolithography, ACS Appl Mater Interfaces, 2017,
9(39), 34314–34324. 10.1021/acsami.7b09223.
[13] Parkatzidis, K., Chatzinikolaidou, M., Kaliva, M., Bakopoulou, A., Farsari, M.,
Vamvakaki, M. Multiphoton 3D printing of biopolymer-based hydrogels, ACS Biomat Sci Eng,
2019, 5(11), 6161–6170. 10.1021/acsbiomaterials.9b01300.
[14] Pekkanen, A. M., Mondschein, R. J., Williams, C. B., Long, T. E. 3D printing polymers with
supramolecular functionality for biological applications, Bio macromolecules, 2017, 18(9),
2669–2687. 10.1021/acs.biomac.7b00671.
[15] Peng, B., Yang, Y., Gu, K., Amis, E. J., Cavicchi, K. A. Digital light processing 3D printing of
triple shape memory polymer for sequential shape shifting, ACS Mat Lett, 2019, 1(4),
410–417. 10.1021/acsmaterialslett.9b00262.
[16] Pyo, S. H., Wang, P., Hwang, H. H., Zhu, W., Warner, J., Chen, S. Continuous optical 3D
printing of green aliphatic polyurethanes, ACS Appl Mater Interfaces, 2017, 9(1), 836–844.
10.1021/acsami.6b12500.
[17] Schultz, A. R., Lambert, P. M., Chartrain, N. A., Ruohoniemi, D. M., Zhang, Z., Jangu, C.,
Zhang, M., Williams, C. B., Long, T. E. 3D printing phosphonium ionic liquid networks with
mask projection microstereolithography, ACS Macro Lett, 2014, 3(11), 1205–1209. 10.1021/
mz5006316.
[18] Wang, Z., Kumar, H., Tian, Z., Jin, X., Holzman, J. F., Menard, F., Kim, K. Visible light
photoinitiation of cell-adhesive gelatin methacryloyl hydrogels for stereolithography 3D
bioprinting, ACS Appl Mater Interfaces, 2018, 10(32), 26859–26869. 10.1021/
acsami.8b06607.
[19] Xue, D., Wang, Y., Zhang, J., Mei, D., Wang, Y., Chen, S. Projection-based 3D printing of cell
patterning scaffolds with multiscale channels, ACS Appl Mater Interfaces, 2018, 10(23),
19428–19435. 10.1021/acsami.8b03867.
[20] Zarek, M., Layani, M., Cooperstein, I., Sachyani, E., Cohn, D., Magdassi, S. 3D printing of
shape memory polymers for flexible electronic devices, Adv Mater, 2016, 28(22), 4449–4454.
10.1002/adma.201503132.
 Chapter 1 Novel photoinitiating systems for 3D printing 43

[21] Cullen, A. T., Price, A. D. Digital light processing for the fabrication of 3D intrinsically
conductive polymer structures, Synth Met, 2018, 235, 34–41.
[22] Chiappone, A., Fantino, E., Roppolo, I., Lorusso, M., Manfredi, D., Fino, P., Pirri, C. F.,
Calignano, F. 3D printed PEG-Based hybrid nanocomposites obtained by sol-gel technique,
ACS Appl Mater Interfaces, 2016, 8(8), 5627–5633.
[23] Mu, Q., Wang, L., Dunn, C. K., Kuang, X., Duan, F., Zhang, Z., Qi, H. J., Wang, T. Digital light
processing 3D printing of conductive complex structures, Addit Manuf, 2017, 18, 74–83.
[24] Al Mousawi, A., Garra, P., Schmitt, M., Toufaily, J., Hamieh, T., Graff, B., Fouassier, J. P.,
Dumur, F., Lalevée, J. 3-Hydroxyflavone and N-Phenylglycine in high performance
photoinitiating systems for 3d printing and photocomposites synthesis, Macromolecules,
2018, 51(12), 4633–4641. 10.1021/acs.macromol.8b00979.
[25] Al Mousawi, A., Poriel, C., Dumur, F., Toufaily, J., Hamieh, T., Fouassier, J. P., Lalevée, J. Zinc
tetraphenylporphyrin as high performance visible light photoinitiator of cationic
photosensitive resins for LED projector 3D printing applications, Macromolecules, 2017,
50(3), 746–753. 10.1021/acs.macromol.6b02596.
[26] Zhang, J., Dumur, F., Xiao, P., Graff, B., Bardelang, D., Gigmes, D., Fouassier, J. P., Lalevée,
J. Structure design of naphthalimide derivatives: Toward versatile photoinitiators for Near-
UV/Visible LEDs, 3D printing, and water-soluble photoinitiating systems, Macromolecules,
2015, 48(7), 2054–2063. 10.1021/acs.macromol.5b00201.
[27] Zhao, J., Lalevée, J., Lu, H., MacQueen, R., Kable, S. H., Schmidt, T. W., Stenzel, M. H., Xiao,
P. A new role of curcumin: As a multicolor photoinitiator for polymer fabrication under
household UV to red LED bulbs, Polym Chem, 2015, 6(28), 5053–5061.
[28] Kim, S. H., Chu, C. C. Fabrication of a biodegradable polysaccharide hydrogel with riboflavin,
vitamin B2, as a photo‐initiator and L‐arginine as coinitiator upon UV irradiation, J Biomed
Mater Res B Appl Biomater, 2009, 91B(1), 390–400.
[29] Encinas, M. V., Rufs, A. M., Bertolotti, S., Previtali, C. M. Free radical polymerization
photoinitiated by riboflavin/amines. effect of the amine structure, Macromolecules, 2001,
34(9), 2845–2847. 10.1021/ma001649r.
[30] Xiao, P., Dumur, F., Graff, B., Fouassier, J. P., Gigmes, D., Lalevée, J. Cationic and thiol-ene
photopolymerization upon red lights using anthraquinone derivatives as photoinitiators,
Macromolecules, 2013, 46(17), 6744–6750.
[31] Zhang, J., Hill, N., Lalevée, J., Fouassier, J.-P., Zhao, J., Graff, B., Schmidt, T. W., Kable, S. H.,
Stenzel, M. H., Coote, M. L., Xiao, P. Multihydroxy-Anthraquinone derivatives as free radical
and cationic photoinitiators of various photopolymerizations under green LED, Macromol
Rapid Commun, 2018, 39(19), 1800172.
[32] Zhang, J., Lalevée, J., Morlet-Savary, F., Graff, B., Xiao, P. Photopolymerization under various
monochromatic UV/visible LEDs and IR lamp: Diamino-anthraquinone derivatives as versatile
multicolor photoinitiators, Eur Polym J, 2018, 591–600.
[33] Zhang, J., Lalevée, J., Mou, X., Morlet-Savary, F., Graff, B., Xiao, P. N-Phenylglycine as a
versatile photoinitiator under Near-UV LED, Macromolecules, 2018, 51(10), 3767–3773.
10.1021/acs.macromol.8b00747.
[34] Wang, G., Hill, N. S., Zhu, D., Xiao, P., Coote, M. L., Stenzel, M. H. Efficient photoinitiating
system based on diaminoanthraquinone for 3D printing of polymer/carbon nanotube
nanocomposites under visible light, ACS Appl Polym Mat, 2019, 1(5), 1129–1135. 10.1021/
acsapm.9b00140.
[35] Zhang, J., Lalevée, J., Zhao, J., Graff, B., Stenzel, M. H., Xiao, P. Dihydroxyanthraquinone
derivatives: Natural dyes as blue-light-sensitive versatile photoinitiators of
photopolymerization, Polym Chem, 2016, 7(47), 7316–7324.
44 D. Zhu et al.

[36] Zhang, J., Lalevee, J., Hill, N. S., Peng, X., Zhu, D., Kiehl, J., Morlet-Savary, F., Stenzel, M. H.,
Coote, M. L., Xiao, P. Photoinitiation mechanism and ability of monoamino-substituted
anthraquinone derivatives as cationic photoinitiators of polymerization under LEDs,
Macromol Rapid Commun, 2019, 40(16), e1900234.
[37] Atala, E., Fuentes, J., Wehrhahn, M. J., Speisky, H. Quercetin and related flavonoids conserve
their antioxidant properties despite undergoing chemical or enzymatic oxidation, Food Chem,
2017, 234, 479–485.
[38] Al Mousawi, A., Garra, P., Dumur, F., Graff, B., Fouassier, J. P., Lalevée, J. Flavones as natural
photoinitiators for light mediated free‐radical polymerization via light emitting diodes, J
Polym Sci, 2020, 58(2), 254–262. 10.1002/pol.20190044.
[39] Gijsman, P. 23 – Polymer Stabilization, Handbook of environmental degradation of materials,
(Second Edition), Kutz, M. Ed, William Andrew Publishing: Oxford, 2012, 673–714.
[40] Lee, T. Y., Guymon, C. A., Jönsson, E. S., Hoyle, C. E. The effect of monomer structure on
oxygen inhibition of (meth)acrylates photopolymerization, Polymer, 2004, 45(18), 6155–6162.
10.1016/j.polymer.2004.06.060.
[41] Boeira, P. O., Meereis, C. T. W., Suárez, C. E. C., de Almeida, S. M., Piva, E., da Silveira Lima,
G. Coumarin-based iodonium hexafluoroantimonate as an alternative photoinitiator for
experimental dental adhesives resin, Appl Adhe Sci, 2017, 5(1), 2. 10.1186/s40563-016-0080-6.
[42] Mokbel, H., Toufaily, J., Hamieh, T., Dumur, F., Campolo, D., Gigmes, D., Pierre Fouassier, J.,
Ortyl, J., Lalevée, J. Specific cationic photoinitiators for near UV and visible LEDs: Iodonium
versus ferrocenium structures, J Appl Polym Sci, 2015, 132, 46.
[43] Li, Z., Zou, X., Shi, F., Liu, R., Yagci, Y. Highly efficient dandelion-like near-infrared light
photoinitiator for free radical and thiol-ene photopolymerizations, Nat Commun, 2019, 10(1),
3560. 10.1038/s41467-019-11522-0.
[44] Abdallah, M., Dumur, F., Hijazi, A., Rodeghiero, G., Gualandi, A., Cozzi, P. G., Lalevée, J.
Keto‐coumarin scaffold for photoinitiators for 3D printing and photocomposites, J Polym Sci,
2020, 10.1002/pol.20190290.
[45] Abdallah, M., Hijazi, A., Graff, B., Fouassier, J.-P., Rodeghiero, G., Gualandi, A., Dumur, F., Cozzi,
P. G., Lalevée, J. Coumarin derivatives as versatile photoinitiators for 3D printing, polymerization
in water and photocomposite synthesis, Polym Chem, 2019, 10.1039/c8py01708e.
[46] Dumur, F. Recent advances on carbazole-based photoinitiators of polymerization, Eur Polym J,
2020, 125, 109503.
[47] Zheng, Y. C., Zhao, Y. Y., Zheng, M. L., Chen, S. L., Liu, J., Jin, F., Dong, X. Z., Zhao, Z. S.,
Duan, X. M. Cucurbit[7]uril-Carbazole two-photon photoinitiators for the fabrication of
biocompatible three-dimensional hydrogel scaffolds by laser direct writing in aqueous
solutions, ACS Appl Mater Interfaces, 2019, 11(2), 1782–1789.
[48] Hu, P., Qiu, W., Naumov, S., Scherzer, T., Hu, Z., Chen, Q., Knolle, W., Li, Z. Conjugated
bifunctional carbazole‐based oxime esters: Efficient and versatile photoinitiators for 3D Printing
under one‐ and two‐photon excitation, ChemPhotoChem, 2020, 10.1002/cptc.201900246.
[49] Al Mousawi, A., Dumur, F., Garra, P., Toufaily, J., Hamieh, T., Graff, B., Gigmes, D., Fouassier,
J. P., Lalevée, J. Carbazole scaffold based photoinitiator/photoredox catalysts: Toward new
high performance photoinitiating systems and application in LED projector 3D printing resins,
Macromolecules, 2017, 50(7), 2747–2758. 10.1021/acs.macromol.7b00210.
[50] Al Mousawi, A., Lara, D. M., Noirbent, G., Dumur, F., Toufaily, J., Hamieh, T., Bui, -T.-T.,
Goubard, F., Graff, B., Gigmes, D., Fouassier, J. P., Lalevée, J. Carbazole derivatives with
thermally activated delayed fluorescence property as photoinitiators/photoredox catalysts
for LED 3D printing technology, Macromolecules, 2017, 50(13), 4913–4926. 10.1021/acs.
macromol.7b01114.
 Chapter 1 Novel photoinitiating systems for 3D printing 45

[51] Al Mousawi, A., Garra, P., Dumur, F., Bui, T. T., Goubard, F., Toufaily, J., Hamieh, T., Graff, B.,
Gigmes, D., Fouassier, J. P., Lalevee, J. Novel carbazole skeleton-based photoinitiators for
LED polymerization and LED projector 3D printing, Molecules, 2017, 22(12), 10.3390/
molecules22122143.
[52] Hu, P., Qiu, W., Naumov, S., Scherzer, T., Hu, Z., Chen, Q., Knolle, W., Li, Z. Conjugated
bifunctional carbazole‐based oxime esters: Efficient and versatile photoinitiators for 3D
Printing under one‐ and two‐photon excitation, ChemPhotoChem, 2020, 224–232.
[53] Qiu, W., Hu, P., Zhu, J., Liu, R., Li, Z., Hu, Z., Chen, Q., Dietliker, K., Liska, R. Cleavable
unimolecular photoinitiators based on oxime‐ester chemistry for two‐photon three‐dimensional
printing, ChemPhotoChem, 2019, 3(11), 1090–1094. 10.1002/cptc.201900164.
[54] Zhou, R., Malval, J.-P., Jin, M., Spangenberg, A., Pan, H., Wan, D., Morlet-Savary, F., Knopf,
S. A two-photon active chevron-shaped type I photoinitiator designed for 3D
stereolithography, Chem Commun, 2019, 55, 6233–6236.
[55] Al Mousawi, A., Garra, P., Dumur, F., Bui, -T.-T., Goubard, F., Toufaily, J., Hamieh, T., Graff, B.,
Gigmes, D., Fouassier, J. Novel carbazole skeleton-based photoinitiators for LED
polymerization and LED projector 3D printing, Molecules, 2017, 22(12), 2143.
[56] Hamama, H. H. 19 – Recent advances in posterior resin composite restorations, Woodhead
Publishing, 2019, 18.
[57] Schricker, S. R. 9 – Composite resin polymerization and relevant parameters, Woodhead
Publishing, 2017, 153–170.
[58] Shah, D. U., Schubel, P. J. Evaluation of cure shrinkage measurement techniques for
thermosetting resins, Polym Test, 2010, 29(6), 629–639.
[59] Garra, P., Graff, B., Morlet-Savary, F., Dietlin, C., Becht, J.-M., Fouassier, J.-P., Lalevée,
J. Charge transfer complexes as pan-scaled photoinitiating systems: From 50 μm 3D printed
polymers at 405 nm to extremely deep photopolymerization (31 cm), Macromolecules, 2017,
51(1), 57–70. 10.1021/acs.macromol.7b02185.
[60] Asmusen, S., Arenas, G., Cook, W. D., Vallo, C. Photobleaching of camphorquinone during
polymerization of dimethacrylate-based resins, Dent Mater, 2009, 25(12), 1603–1611.
[61] Abdallah, M., Le, H., Hijazi, A., Schmitt, M., Graff, B., Dumur, F., Bui, -T.-T. A., Goubard, F.,
Fouassier, J.-P., Lalevée, J. Acridone derivatives as high performance visible light
photoinitiators for cationic and radical photosensitive resins for 3D printing technology and
for low migration photopolymer property, Polymer, 2018, 159, 47–58.
[62] Garra, P., Caron, A., Al Mousawi, A., Graff, B., Morlet-Savary, F., Dietlin, C., Yagci, Y.,
Fouassier, J.-P., Lalevée, J. Photochemical, thermal free radical, and cationic polymerizations
promoted by charge transfer complexes: Simple strategy for the fabrication of thick
composites, Macromolecules, 2018, 51(19), 7872–7880. 10.1021/acs.macromol.8b01596.
[63] Abdallah, M., Hijazi, A., Graff, B., Fouassier, J.-P., Rodeghiero, G., Gualandi, A., Dumur, F.,
Cozzi, P. G., Lalevée, J. Coumarin derivatives as versatile photoinitiators for 3D printing,
polymerization in water and photocomposite synthesis, Polym Chem, 2019, 872–884.
[64] Baralle, A., Garra, P., Graff, B., Morlet-Savary, F., Dietlin, C., Fouassier, J. P., Lakhdar, S.,
Lalevée, J. Iodinated polystyrene for polymeric charge transfer complexes: Toward
high-performance near-UV and visible light macrophotoinitiators, Macromolecules, 2019,
52(9), 3448–3453. 10.1021/acs.macromol.9b00252.
[65] Wang, D., Garra, P., Lakhdar, S., Graff, B., Fouassier, J. P., Mokbel, H., Abdallah, M., Lalevée,
J. Charge transfer complexes as dual thermal and photochemical polymerization initiators for
3D printing and composites synthesis, ACS Appl Polym Mat, 2019, 1(3), 561–570. 10.1021/
acsapm.8b00244.
[66] Palmer, B. J., Kutal, C., Billing, R., Hennig, H. A new photoinitiator for anionic polymerization,
Macromolecules, 1995, 28(4), 1328–1329. 10.1021/ma00108a078.
46 D. Zhu et al.

[67] Al Mousawi, A., Kermagoret, A., Versace, D.-L., Toufaily, J., Hamieh, T., Graff, B., Dumur, F.,
Gigmes, D., Fouassier, J. P., Lalevée, J. Copper photoredox catalysts for polymerization upon
near UV or visible light: Structure/reactivity/efficiency relationships and use in LED projector
3D printing resins, Polym Chem, 2017, 8, 568–580.
[68] Lim, K. S., Schon, B. S., Mekhileri, N. V., Brown, G. C. J., Chia, C. M., Prabakar, S., Hooper,
G. J., Woodfield, T. B. F. New visible-light photoinitiating system for improved print fidelity in
gelatin-based bioinks, ACS Biomat Sci Eng, 2016, 2(10), 1752–1762. 10.1021/
acsbiomaterials.6b00149.
[69] Lalevéé , J., Blanchard, N., Tehfe, M.-A., Morlet-Savary, F., Fouassier, J. P. Green bulb light
source induced epoxy cationic polymerization under air using Tris(2,2′-bipyridine)ruthenium(II)
and silyl radicals, Macromolecules, 2010, 43(24), 10191–10195.
[70] Iwai, K., Uesugi, Y., Sakabe, T., Hazama, C., Takemura, F. Tris(1,10-phenanthroline)ruthenium(II)-
and Tris(2,2′-bipyrazine)ruthenium(II)-Sensitized Photopolymerization of Acrylamide, Polym
J, 1991, 23(6), 757–763. 10.1295/polymj.23.757.
[71] Versace, D.-L., Cerezo Bastida, J., Lorenzini, C., Cachet-Vivier, C., Renard, E., Langlois, V.,
Malval, J.-P., Fouassier, J.-P., Lalevée, J. A Tris(triphenylphosphine)ruthenium(II) Complex as a
UV Photoinitiator for Free-Radical Polymerization and in Situ Silver Nanoparticle Formation in
Cationic Films, Macromolecules, 2013, 46(22), 8808–8815.
[72] Chi, T., Somers, P., Wilcox, D. A., Schuman, A. J., Iyer, V., Le, R., Gengler, J., Ferdinandus, M.,
Liebig, C., Pan, L., Xu, X., Boudouris, B. W. Tailored thioxanthone‐based photoinitiators for
two‐photon‐controllable polymerization and nanolithographic printing, J Polym Sci B Polym
Phys, 2019, 57(21), 1462–1475. 10.1002/polb.24891.
[73] Lai, H., Zhu, D., Xiao, P. Yellow triazine as an efficient photoinitiator for polymerization and
3D printing under LEDs, Macromol Chem Phys, 2019, 220(18), 10.1002/macp.201900315.
[74] Al Mousawi, A., Garra, P., Sallenave, X., Dumur, F., Toufaily, J., Hamieh, T., Graff, B., Gigmes,
D., Fouassier, J. P., Lalevée, J. π-Conjugated dithienophosphole derivatives as high
performance photoinitiators for 3D printing resins, Macromolecules, 2018, 51(5), 1811–1821.
10.1021/acs.macromol.8b00044.
[75] Zhang, J., Lalevée, J., Hill, N. S., Launay, K., Morlet-Savary, F., Graff, B., Stenzel, M. H.,
Coote, M. L., Xiao, P. Disubstituted aminoanthraquinone-based multicolor photoinitiators:
Photoinitiation mechanism and ability of cationic polymerization under blue, green,
yellow, and red LEDs, Macromolecules, 2018, 51(20), 8165–8173. 10.1021/acs.
macromol.8b01763.
[76] Abdallah, M., Le, H., Hijazi, A., Schmitt, M., Graff, B., Dumur, F., Bui, -T.-T., Goubard, F.,
Fouassier, J.-P., Lalevée, J. Acridone derivatives as high performance visible light
photoinitiators for cationic and radical photosensitive resins for 3D printing technology and
for low migration photopolymer property, Polymer, 2018, 159, 47–58, 10.1016/j.
polymer.2018.11.021.
[77] Tromayer, M., Gruber, P., Markovic, M., Rosspeintner, A., Vauthey, E., Redl, H., Ovsianikov,
A., Liska, R. A biocompatible macromolecular two-photon initiator based on hyaluronan,
Polym Chem, 2017, 8(2), 451–460. 10.1039/c6py01787h.
[78] Metral, B., Bischoff, A., Ley, C., Ibrahim, A., Allonas, X. Photochemical study of a
three‐component photocyclic initiating system for free radical photopolymerization:
Implementing a model for digital light processing 3D printing, ChemPhotoChem, 2019, 3(11),
1109–1118. 10.1002/cptc.201900167.
[79] Zhang, J., Launay, K., Hill, N. S., Zhu, D., Cox, N., Langley, J., Lalevée, J., Stenzel, M. H.,
Coote, M. L., Xiao, P. Disubstituted aminoanthraquinone-based photoinitiators for free
radical polymerization and fast 3D printing under visible light, Macromolecules, 2018,
10.1021/acs.macromol.8b02145.
 Chapter 1 Novel photoinitiating systems for 3D printing 47

[80] Zhang, J., Launay, K., Hill, N. S., Zhu, D., Cox, N., Langley, J., Lalevée, J., Stenzel, M. H.,
Coote, M. L., Xiao, P. Disubstituted aminoanthraquinone-based photoinitiators for free
radical polymerization and fast 3D printing under visible light, Macromolecules, 2018,
10104–10112. 10.1021/acs.macromol.8b02145.
[81] Christmann, J., Allonas, X., Ley, C., Ibrahim, A., Croutxé-Barghorn, C. Triazine-Based type-ii
photoinitiating system for free radical photopolymerization: Mechanism, efficiency, and
modeling, Macromol Chem Phys, 2017, 218(18), 1600597.
[82] Zhang, J., Xiao, P., Morlet-Savary, F., Graff, B., Fouassier, J. P., Lalevée, J. A known
photoinitiator for a novel technology: 2-(4-methoxystyryl)-4,6-bis(trichloromethyl)-1,3,5-
triazine for near UV or visible LED, Polym Chem, 2014, 5(20), 6019–6026.
[83] Wang, J., Stanic, S., Altun, A. A., Schwentenwein, M., Dietliker, K., Jin, L., Stampfl, J., Baudis,
S., Liska, R., Grutzmacher, H. A highly efficient waterborne photoinitiator for visible-light-
induced three-dimensional printing of hydrogels, Chem Commun (Camb), 2018, 54(8),
920–923. 10.1039/c7cc09313f.
[84] Wang, J., Chiappone, A., Roppolo, I., Shao, F., Fantino, E., Lorusso, M., Rentsch, D., Dietliker,
K., Pirri, C. F., Grutzmacher, H. All-in-One cellulose nanocrystals for 3D printing of
nanocomposite hydrogels, Angew Chem Int Ed Engl, 2018, 57(9), 2353–2356. 10.1002/
anie.201710951.
[85] Pawar, A. A., Halivni, S., Waiskopf, N., Ben-Shahar, Y., Soreni-Harari, M., Bergbreiter, S.,
Banin, U., Magdassi, S. Rapid three-dimensional printing in water using semiconductor-metal
hybrid nanoparticles as photoinitiators, Nano Lett, 2017, 17(7), 4497–4501. 10.1021/acs.
nanolett.7b01870.
[86] Xing, J.-F., Zheng, M.-L., Duan, X.-M. Two-photon polymerization microfabrication of
hydrogels: An advanced 3D printing technology for tissue engineering and drug delivery,
Chem Soc Rev, 2015, 44, 5031–5039.
Shixiong Chen, Ruchun Zhou, Ming Jin
Chapter 2
New free radical and cationic photoinitiators
for two-photon 3D printing
2.1 Introduction
Two-photon absorption (TPA) – the simultaneous absorption of two photons by the
same molecule – was analyzed and predicted theoretically by Göppert-Mayer in
1931 [1]. However, the experimental evidence was firstly provided by Kaiser and
Garrett in 1961 [2], soon after the invention of the laser. Later, the up-converted las-
ing was found in some organic dyes such as Rhodamine 6G [3], Rhodamine B [4]
and Xanthalene [5]. But due to the poor TPA ability, these special properties were
not wildly used. The research of TPA materials and their application vastly im-
proved since the 1990s. On the one hand, TPA became easier to investigate, as sub-
picosecond pulsed lasers (particularly the Ti:sapphire laser) became more readily
available. On the other hand, many novel multi-functionalized organic dyes with
good TPA properties were synthesized [6]. Nowadays, organic molecules [7–9], mac-
romolecules [10, 11] and organo-metallic complexes [12–14] are the mostly reported
two-photon materials due to their good TPA properties.
Compared to one photon absorption (OPA), there are several advantages for TPA.
First, compared to OPA, the irradiation wavelength is longer. The linear loss and the
Rayleigh scattering are weaker, resulting in better transmission. Additionally, the
damage caused by the irradiating light is less due to the lower photon energy. Last
but not the least, the spatial selectivity of TPA is much better than linear absorption.
There is now a strong demand for efficient TPA molecules for a wide range of appli-
cations, including microscopy [15–17], microfabrication [18–20], three-dimensional data-
storage [21, 22], optical power limiting [23], up-converted lasing [24, 25], photodynamic
therapy [26–28], fluorescent probes [29, 30] and the localized release of bio-active species
[31, 32]. Among the applications involving three-dimensional microstructure construc-
tion, two-photon polymerization (TPP) into which polymerization is initiated by the TPA
is mostly used to prepare materials.
The TPP reaction mechanism is shown in Figure 2.1. Compared to one photon
polymerization (OPP), the size resolution of samples prepared from TPP is better
due to the higher spatial selectivity. Since the TPA is nonlinear, the probability of
these absorption events falls off quickly, away from the focal point of laser light.

Shixiong Chen, Ruchun Zhou, Ming Jin, Department of Polymer Materials, School of Materials
Science and Engineering, Tongji University, Shanghai, P. R. China

https://doi.org/10.1515/9783110570588-002
50 Shixiong Chen, Ruchun Zhou, Ming Jin

Figure 2.1: The Jablonski diagram of photosensitive molecule where (a) an electron in the
photoinitiator can become excited from the ground state (S0) to an excited state (S1) either by
linear absorption (blue line) or TPA (red line); (b) the active species generation routes at triplet
state and (c) the active species generation routes at singlet state.

This means that the reaction is highly localized to a single point in space and can
be smaller than the diffraction limit. Thus, TPP is more effective in microfabrica-
tion. The only difference between TPP and OPP is the irradiation path from ground
state to excited state. In other words, the properties of the excited state of the pho-
tosensitive molecule are the same in the two fabrication processes.
Similar to that of OPP, the rate of polymerization in TPP is mainly decided by
the absorption property of initiation systems (photoinitiators, co-initiators or photo-
sensitizers), the generation rate of active species and the rate of initiating monomer
polymerization. The absorption property or TPA cross section (δ) of photosensitive
molecules is the most important parameter. Initiation system with a higher δ can
initiate polymerization more efficiently; that is, high writing speeds, low polymeri-
zation thresholds and high-quality resulting structures. In 2004, the δ of commer-
cial photoinitiators was systematically characterized by Belfield, Schafer and their
coworkers [33]. They found that the TPA of commercial initiators is low (less than
20GM). Molecules containing (a) large and rigid conjugation structure, (b) donor
and acceptor groups at the center and ends of the molecule and (c) dipolar push-
pull-systems, quadrupolar, octupolar and more generally branched/multipolar TPA
chromophores (even dendritic and polymeric TPA active compounds) are favorable
in high two-photon absorption ability, which was first announced by Pawlicki and
his coworkers in 2009 [34]. Since then, many organic molecules with large δ have
been synthesized. We now introduce the novel two-photon initiators developed in
the recent years and their applications related to 3D printing and microfabrication.
 Chapter 2 New free radical and cationic photoinitiators for two-photon 3D printing 51

2.2 Two-photon free-radical photoinitiator

Free radical polymerization is wildly used in the preparation of a polymer. It can be
applied in many processing conditions except in oxygen containing environments, es-
pecially in aqueous environments [35]. As mentioned earlier, the δ of photoinitiator is
of great importance for TPP. Thus, the photoinitiation system for free radical polymeri-
zation with large δ is one of the most important research fields. In 1998, Albota et al.
[36] reported the design strategies and studied the structure-property relationships to
obtain the organic molecules with large δ. They proved that the δ was related to the
symmetric charge transfer conjugation length, as is shown in Scheme 2.1.

Scheme 2.1: The molecule structure and related TPA properties of the compounds studied by
Albota (there is a large uncertainty in this δ value because of a large uncertainty in the rather low
value of Φf, which is 0.0055 (±45%)).
52 Shixiong Chen, Ruchun Zhou, Ming Jin

Li et al. [37] designed and synthesized a series of carbazole-based Schiff bases

(Figure 2.2(a)) with long conjugation length that are used as two-photon initiators
(TPIs) using a simple and economical synthetic route. In this method, the N=C
bonds worked as π bridges. The method simultaneously introduced different elec-
tron donor/acceptor groups in the molecules to form the D-π-D-π-D, A-π-D-π-A
structures. The TPIs exhibited bathochromic absorption up to 415 nm (Figure 2.2(b))
and enhanced two-photon absorption at 800 nm. Lower threshold energy was ex-
hibited by the synthesized TPIs than the commercial Irgacure 369 and IP-L, as is
shown in Figure 2.2(c), which considerably favored two-photon-induced microfabri-
cation (corresponding δ is shown in Figure 2.2(c)).
Qiu et al. [38] obtained three unimolecular TPIs (OEC3-1, OEC3-2 and OEC4,
Figure 2.3(a)) containing the coumarin moieties for enhancing TPA and oxime esters for
producing initiation groups. The TPIs here have much higher δ compared to the refer-
ence compounds (TPO and M2CMK) in Table 2.1. OEC3-2 showed a low threshold laser
power for polymerization and a broad processing window similarity to the reported
highly efficient two-photon initiator M2CMK. These properties benefit the two-photon 3D
printing of complex 3D microstructures high resolution, as is shown in Figure 2.3(b, c).
Cao et al. [39] reported a new series of chromophores (TPAQ, TPABQ, EOQ and
EOBQ, Figure 2.4(a)) to improve δ. Each of the four molecules has an anticipated red
shift maxima absorption between 350–470 nm because of the conjugation expansion.
An appropriate π-conjugation degree is necessary for high δ, which was supported by
the results that TPABQ with a larger π-conjugation structure has a far lower δ2PA com-
pared to TPAQ in the 780–820 nm range. Additionally, the TPAQ showed a far better
performance than the common photoinitiator benzil in Two-photon initiating poly-
merization (TPP) used as a photoinitiator, as is shown in Figure 2.4(c–f).
Pucher et al. [40] presented a series of cross-conjugated D-π-A-π-D-based 2PIs
(Scheme 2.2) with different donor and acceptor groups to evaluate the structure-
activity relationship. All of them showed high extinction coefficients at around 400
nm with hardly any emission quantum yields, and relatively broad processing win-
dows for two-photon-induced microfabrication, as is shown in Table 2.2. A fine mi-
crostructure was obtained with line widths of about 250 nm and PI concentrations
of about 0.05 wt%, as is shown in Figure 2.5.
Lu et al. [41] designed a novel two-photon photoinitiator with a radical quench-
ing moiety (BNMBC, Figure 2.6(a)), which was devised for high efficiency TPP initia-
tion, while confining radical diffusion. By using Z-scan measurement, the δ of
BNMBC showed a high value of 2,367GM. It has been proved that a high two-photon
-induced photopolymerization (TPIP) initiating efficiency and an effective radical
quenching effect (Figure 2.6(c)), benefit the fabrication of precise structures. Malval
et al. [42] investigated a new chevron-shaped hybrid anthracene-thioxanthone
(ANTX) system, which retained the high efficiency in photo-inducing free radical
polymerization and significantly increased the δ. The polymerization profits and
laser direct writing results are shown in Figure 2.7.
 Chapter 2 New free radical and cationic photoinitiators for two-photon 3D printing 53

Figure 2.2: (a) The structures of carbazole-based Schiff bases; (b) UV–vis absorption spectra of the
TPIs measured in chloroform; (c) TPP processing window of all investigated TPIs and references
under irradiation of a 800 nm pulsed laser (PIs concentration: 5.2 × 10−6 mol g−1 resin, writing
speed: 60 μm s−1). Reproduced with permission from [37]. Copyright 2018, John Wiley and Sons.
54 Shixiong Chen, Ruchun Zhou, Ming Jin

(a) O
N O R
O N
O

O O O O

N OEC4 N OEC3–1 R = phenyl

OEC3–2 R = vinyl

(b) (c)

OEC3–1
10 μm
OEC3–2
(d)
OEC4

M2CMK

8 12 16 20 24 28 32
Laser power (mW) 20 μm

Figure 2.3: (a) The structures of coumarin-based oxime esters; (b) Two‐photo 3D printing screening
tests with PI concentration: 1.1 × 10−5 mol/g resin and writing speed: 750 μm/s. SEM images of
(c) one geometric structure and (d) four geometric structures of OEC3‐2 produced via two‐photon
3D printing. Reproduced with permission from [38]. Copyright 2019, John Wiley and Sons.

Table 2.1: Photophysical properties of the TPIs synthesized by Qiu [38].

TPIs λmax/nma ελmax/L mol− cm− ε nm/L mol− cm− δ nm/GMa

OCE-  , , 

OCE-  , , 
OCE  , , 
MCMK  , – 

δ at 800 nm
a

δ at 600 nm from the literature

b

Xue et al. [43] synthesized two coumarin-containing benzylidene cyclopenta-

none dyes (1 and 2, referred BDMA, Scheme 2.3) as TPI through a simple route. The
successful TPP fabrications were taken and 2 used as the initiator with high photo-
sensitizing efficiency, as is shown in Figure 2.8.
Fitilis et al. [44] reported two TPA photoinitiators-sensitizers with fluorene as
the core structure for TPP of a diacrylate. They mainly investigated the influence on
polymerization properties of different resin, the laser power and writing speed, and
 Chapter 2 New free radical and cationic photoinitiators for two-photon 3D printing 55

(a)

N N N N

N N N N

TPAQ TPABQ

N N

N N

O O

O O
EOQ
(b) EOBQ
200
EOQ
EOBQ
TAPQ
150 TPABQ
TPA Cross Section (GM)

100

50

0
720 740 760 780 800 820 840 860 880 900
Wavelength (nm)

Figure 2.4: (a) The structures of benzil-type compounds; (b) Two-photon excitation spectra of the
target compounds in CHCl3; (c) SEM images of TPAQ (c), TPABQ (d) and benzil (e) after polymerization.
The laser powers used to fabricate lines are shown on the SEM images in the power range of 0.8–5.5
mW. The scan speed is 10 m s−1. (f) SEM image of a photonic crystal using TPAQ as photoinitiator
(0.5%), MMA (48%) and DPE-6A (51.5%). Scale bar is 2 μm. Reproduced with permission from [39].
Copyright 2009, Royal society of Chemistry.
56 Shixiong Chen, Ruchun Zhou, Ming Jin

(c) 2.7 2.6 2.2 1.8 1.7 1.4 1.2 1.0 0.8 (d) 4.6 4.2 4.0 3.7 3.5 3.2 2.7 2.6

(e) 5.5 5.1 4.6 4.2 4.0 3.7 3.5 3.2 (f)

Figure 2.4 (continued )

Scheme 2.2: The structures of new TPA PIs and reference compounds.

the Numerical Aperture (NA) of focusing and determined the optimum polymeriza-
tion conditions, as is shown in Figure 2.9.
Li et al. [45] summarized a series of D-π-A-π-D type aromatic ketone-based
TPIs (molecule structure and corresponding photophysical properties are shown
in Scheme 2.4). As is shown in Figure 2.10, the TPIs can be applied in two-photon
induced 3D printing.
Chi et al. [46] tailed a great number of thioxanthone-based TPIs with extended
conjugation to get a bathochromic shift, as is shown in Figure 2.11. Besides, there
 Chapter 2 New free radical and cationic photoinitiators for two-photon 3D printing 57

Figure 2.5: 3D structures (resin ETA/TTA 1:1, B3K as initiator) using different laser systems: system A
(1 kHz): (a) dragonfly; (b) dinosaur; system B (100 MHz): (c) woodpile structure; (d) detailed view of the
woodpile structure. Reproduced with permission from [40]. Copyright 2009, American Chemistry Society.

Table 2.2: Detailed photophysical data of TPIs in

Pucher’s work [40].

TPIs λmax/nma ελmax/L mol− cm−a δ nm/GMb

HK  , –

OK  , <
MK  , 
BK  , 
PK  , 
MK  , c
MP  , 
MP+  , -d
a
measured in acetonitrile
b
measured in THF
c
The broad signal may cause a certain error
d
not measured due to the poor solubility
58 Shixiong Chen, Ruchun Zhou, Ming Jin

Polymer
w

Formed polymer

Polymer chain
Quencher
Development
Development
Development

Propagation & Termination

Radical
Focused light spot

Quenched radical
BNMBC
BNBC+PhOMe

BNMBC
BNBC

Photoinitiator

BNBC
Initiating

Propagation direction
activated PI
Photoactivation

Resin
(c)
Initiating group

Quenching group

Two-photon-induced initiator
NO2

5 μm
O
O2N

(b)
(a)

Figure 2.6: (a) The chemical structure of photoinitiator; (b) SEM images of a fly fabricated with a
laser power of 7.70 mW and a scan speed of 66 μm s−1 on the photoresist R6. Scale bars are 5 μm;
(c) Mechanism on confining radical diffusion in TPIP. Reproduced with permission from [41].
Copyright 2011, Royal Society of Chemistry.
 Chapter 2 New free radical and cationic photoinitiators for two-photon 3D printing 59

Figure 2.7: SEMs of a microstructure fabricated by TPIP upon excitation at 532 nm. (a) Inset: model
master and the molecule structure of TPI. (b) Arrays of microdots written (λexc: 532 nm; power:
1.5 mW; NA: 0.64) in diacrylate formulations of Ebecryl 605 with (ANTX/ MDEA, 0.08 wt%/4 wt%)
and (DAF, 0.20 wt%). Adapted with permission from [42]. Copyright 2011, American Chemistry
Society.
60 Shixiong Chen, Ruchun Zhou, Ming Jin

Scheme 2.3: The structures of TPIs and coinitiators in Xue’s work.

was an increase in the δ of TPIs increased as well as the TPP properties, as is shown
in Table 2.3.
In 2019, Hu et al. [47] facile synthesized several conjugated ketocarbazoles for
efficient 2PP (4c, 5c and 6c, Figure 2.12(a)). All molecules showed an obvious pho-
tobleaching and had much lower threshold energy than commercial TPO and IP-L
(shown in Figure 2.14(b)). In 2020 [48], they considered photo-induced direct
cleavage as another efficient approach to TPP. They designed four bifunctional
carbazole-based oxime esters for active radicals after photodecarboxylation,
which could be used in 3D printing under two-photon excitation, as is shown in
Figure 2.13.
Besides large two-photon cross section, Leander Poocza et al. [49] considered
the solubility of the PI in the macromonomers as a critical factor. They introduced
some polar side chains on the cyclopentanone-based PIs (BDEA and BA740,
Scheme 2.5) to improve the solubility in the monomer urethanedimethacrylate. The
TPP profits are shown in Figure 2.14.
For photocleavage concept, Zhou et al. [50] presented a novel chevron-shaped
type I TPI (OXE, Figure 2.15(a)). By comparing with TPO-L, OXE showed a better 2PP
performance than the reference system and proved the chevron-shaped design
strategy. (OXE ~ 90GM at 720 nm)
Much effort has gone in to get the TPP microfabrication of cytocompatible scaf-
folds with the conventional commercial photoinitiators. For example, the inorganic-
organic hybrid formulations containing Irgacure 369 are commercially available
[51, 52] and some hydrophilic constructs can be obtained by TPP photoinduced by
 Chapter 2 New free radical and cationic photoinitiators for two-photon 3D printing 61

1.05 1.09 1.14 1.21 1.28 1.35 1.42 1.49 1.68 1.882.11 2.34 0.44 0.46 0.48 0.51 0.53 0.55 0.57 0.59 0.72 0.84 0.99

(d)

2μm
Incident energy (mW)
3μm
(b)

69
345 299 253 207 161 115
Incident energy (mW)

Scan speed (m/s)

483 437 391
2μm

1μm
(a)

(c)

Figure 2.8: 2D nanopattern fabricated in R1 (a) and R3; (b) by changing the incident energy with a
fixed line scan speed of 10 μm/s, and in R2; (c) by adjusting the line scan speed with fixed incident
energy of 1.6 mW; and (d) 3D wood pile structure fabricated in R1 with 1.1 mW power and 44 μm/s
scan speed. R1: monomer/Dye-2=99.9/0.1; R2: monomer/Dye-2/o-Cl-HABI/MMT=97.99/0.01/1/1;
R3: monomer/Dye-2/HABI/MMT=97.9/0.1/1/1. Reproduced with permission from [43]. Copyright
2008, Elsevier.
62 Shixiong Chen, Ruchun Zhou, Ming Jin

10μm
2μm

10μm

20μm

10μm
(g)
(e)

(f)

CH2
N
N
O

O
O

Diacrylate monomer

CH3
O

Co-initiator (DIDMA)
CH3
C6H13 C6H13

C6H13 C6H13

H3C CH3

CH3
F(PHT)2

F(TPA)2

CH3 N
H3C

H3C
O
O

O
O
O

H2C
N

N
(a)

(b)

(d)
(c)

Figure 2.9: Chemical structures of (a, b) the two fluorenes; (c) the diacrylate monomer; (d) the
co-initiator; (e and f) SEM images of a 3D lattice fabricated using resin R4 under a plane view and at
45° (writing power: 6 mW, writing speed: 10 μm/s). (g) SEM image of single polymerized lines used
to measure the lateral and axial resolution (writing speed: 50 μm/s; Tthe laser power increases
from the upper towards the lower line). The perpendicular thick polymerized walls support the
single horizontal lines. Reproduced with permission from [44]. Copyright 2010, Elsevier.
 Chapter 2 New free radical and cationic photoinitiators for two-photon 3D printing 63

Scheme 2.4: The structures and related TPA properties of TPIs in Li’s work.
64 Shixiong Chen, Ruchun Zhou, Ming Jin

Figure 2.10: 3D structures (resin ETA/TTA 1:1, B3FL as initiator): (a) St. Stephen’s Cathedral;
(b) Tarantula Spider; (c) detail of the London Tower Bridge; (d) detailed view of the woodpile
structure. Reproduced with permission from [45]. Copyright 2011, John Wiley and Sons.

hydrophobic UV photoinitiators [53, 54]. Comprehensive lists of commonly used TPP

photoinitiators are found in the reference of Torgersen et al. [55] and Song et al. [56].
They are shown in Table 2.4.
Li et al. [57] introduced three new cyclic benzylidene ketone-based molecules
with carboxylic acid sodium salts as water-soluble TPIs (P2CK, G2CK and E2CK,
Scheme 2.6). All three TPIs showed broad processing windows in TPIP screening
tests and yielded higher cytocompatibility than Irgacure 2,959 in cell culture and
MTT assay, both in the case of MG63 and OEC. (shown in Figure 2.16)
Huang et al. [58] synthesized a series of benzylidene cyclanone dyes and im-
proved the water solubility via salification of carboxylic acid sodium (T1–T3,
Scheme 2.7) and these TPIs also showed a favorable biocompatibility in the cytotox-
icity study (the TPP profits are shown in Figure 2.17). To fabricate biosafety materi-
als, they focused on the low-mobility visible light photoinitiators by introducing
polymerizable double bonds onto the molecular structures [59] (PBDA, Scheme 2.6).
The acryloyl groups can help PBDA connect to polymer matrices and reduce the
small molecular migration, thus improving the biocompatibility of the final poly-
meric samples. The TPP profits are shown in Figure 2.18.
Figure 2.11: The predicted UV–Vis absorption spectra and the structures of TPIs in Chi’s work. Reproduced with permission from [46]. Copyright 2019,
John Wiley and Sons.
Chapter 2 New free radical and cationic photoinitiators for two-photon 3D printing
65
66 Shixiong Chen, Ruchun Zhou, Ming Jin

Table 2.3: Two-photon absorption cross section δ and

writing threshold of photoinitiators.

TPIs δ/GMa Writing threshold

( molecules mW−)

BDAPT  (±) .

DANT  (±) .
ITX  (±.) .
DAPT  (±) -b
DBTX  (±) -b
a
The values in parentheses indicate one standard
deviation from the average measured value
b
Difficulty dissolving this material uniformly in the monomer

O
(a) (b)
4c
δ⁓357 GM
N N 5c
4c δ⁓377 GM
O
6c
δ⁓340 GM
N N
5c TPO

N N IP-L
10 15 20 25 30 35 40
O Laser power (mW)
6c

Figure 2.12: (a) Molecular structure of TPIs synthesized by Hu in 2019; (b) TPP processing window
of all investigated TPIs (shown in Figure 2.14(a)) and references under irradiation of a 780 nm
pulsed laser (PIs concentration: 1.3 × 10−6 mol PI/g resin). Reproduced with permission from [47].
Copyright 2019, The Society of Photopolymer Science and Technology.

Zheng et al. [60] reported a water-soluble host − guest complex two-photon

photoinitiator (BMVPC and CB7, Figure 2.19(a)). The related photophysical proper-
ties are shown in Table 2.5. The complex simultaneously realized the large TPA
cross section and biocompatibility, allowing for the fabrication of low cell toxicity
hydrogel structures. The TPP also attained a low laser threshold of 4.5 mW and
high fabricating resolution of 180 nm (shown in Figure 2.19(b, c)).
 Chapter 2 New free radical and cationic photoinitiators for two-photon 3D printing 67

(a)

O N O
N
O 4a, 4b O
Z Z

O N N O
Z N Z
O O

4c, 4d
4a, 4c Z = phenyl 4b, 4d Z = vinyl
(b)

4a
δ ⁓ 122 GM
4b
δ ⁓ 102 GM
4c
δ ⁓ 125 GM
4d
δ ⁓ 136 GM

TPO

IP-L
5 10 15 20 25 30 35 40
Laser power (mW)

(c)

10 μm

Figure 2.13: (a) Structures of the novel TPIs synthesized by Hu [48]. (b) Two‐photon 3D printing
processing window of the investigated PIs and references (PIs concentration: 1.3 × 10−6 mol PI/g
resin); (c) SEM picture of the microfabricated structure under a 800 nm pulsed laser irradiation
using 4 d as a PI. Reproduced with permission from [48]. Copyright 2020, John Wiley and Sons.
68 Shixiong Chen, Ruchun Zhou, Ming Jin

Scheme 2.5: The structures of TPIs in Poocza’s work.

2.3 Two-photon cationic photoinitiators

The application of two-photon induced cationic polymerization in microfabrication
was first reported by Belfield and his coworkers in 2000 [61]. The fluorene-based
molecules and iodonium salts were used as photoinitiation system. In 2002, Perry
and Marder synthesized a two-photon–activatable photoacid generator based on a
bis[(diarylamino)styryl]benzene core with covalently attached sulfonium moieties
[62]. The photoacid generator has both a large two-photon absorption cross section
and a high quantum yield of photoacid generation (ΦH+). This photoacid generator
was used in conjunction with a positive-tone chemically amplified resist for the fab-
rication of a three-dimensional (3D) microchannel structure. The basic mechanism
of two-photon induced cationic photoinitiation system is the intramolecular/inter-
molecular charge transfer. Since then, the dyes or photoacid generators with large δ
were synthesized and applied in two-photon microfabrication.
In 2015, Jin and Wu [63] synthesized a series of two-photon sensitive benzene
oligomer-containing D-π-A type sulfonium salts (PAG-1 to PAG-4). These PAGs are di-
polar molecules, which showed good LED sensitivity as well as non-linear absorption
properties (δ at 780 nm is in the range of 184GM to 474GM, as is shown in Table 2.6).
By changing 4-cyanobenzyl into benzyl groups in the sulfonium salts, the ΦH+ of four
PAGs are all more than 0.60. By the laser-scanning lithography (LSL) at 780 nm, pho-
toresists SU-8 can be effectively two-photon polymerized by PAG-3. This polymeriza-
tion occurs only near the focus of a laser beam, as is shown in Figure 2.20.
In 2016, Wu et al. [64] synthesized a series of one/two-branched A-π-D-π-A-type
PAGs. These dipole or quadrupole molecules showed good linear and non-linear ab-
sorption properties. Besides, the two-branched structures collectively showed two-
fold higher H+ production abilities and improved two-photon absorption cross
sections compared to those in the corresponding mono-branched PAGs, as is shown
in Table 2.1. Among the four PAGs (PAG-5 to PAG-8), PAG-8 performed best and it
was used in the microfabrication with SU-8, as is shown in Figure 2.21.
 Chapter 2 New free radical and cationic photoinitiators for two-photon 3D printing 69

Figure 2.14: Results of TPP structuring with different PIs: (a) IC907, (b) IC369 and (c) BA740. (d) CAD
simulated Schwarz P unit cell (side and plan view). (e) Representative SEM micrograph (plan view
of Schwarz P unit cells with 250 μm) of BA740 (0.2%) in LCM (highlighted in gray). The colored
circles represent the obtained results in the heat maps (a–c). Dark Red: bulk polymerization, loss
of structure; Red: bulk polymerization is sealing the pores; Yellow: most precise 3D Schwarz P
structure, best TPP writing conditions; Blue: polymerized structures are not stable/load bearing;
With x: not a single trace of polymerization, no TPP writing possible. Reproduced with permission
from [49]. Copyright 2017, John Wiley and Sons.
70 Shixiong Chen, Ruchun Zhou, Ming Jin

Figure 2.15: (a) The structures of TPIs in Zhou’s work; (b) SEM micrographs of representative 3D
pyramidal structures fabricated by 2P induced polymerization (λirr: 800 nm). Reproduced with
permission from [50]. Copyright 2019, Royal Society of Chemistry.

2.4 Two-photon sensitizers and their initiation

system
In molecules, large δ is often related to the large conjugation structure and large
intramolecular electron transfer, which will also lead to the low energy of π* or-
bital. For PAGs, especially for the onium salts, the lower energy of π* orbital (Eπ*)
will weaken the photochemistry reaction rates due to the lower energy gap between
π* and σ* orbitals. Moreover, when the energy of π* is lower than that of σ* orbitals,
the molecules will not generate acid. Thus, it is difficult to design the molecule with
large δ (more than 500GM) and high ΦH+ (more than 0.40). So, compared to the
one-component initiation system described earlier, the multicomponent initiation
system is more common. In the multicomponent initiation systems, the sensitizer
with a large two-photon absorption cross section will undergo redox reaction with
another molecule (usually the onium salt with a short-wavelength absorption or the
Table 2.4: The water soluble, availability and δ at 800 nm measured using Z-scan analysis of TPIs [55, 56].

TPIs Water soluble Commercial δ nm (GM) Chemical structure

Irgacure  No Yes 

N
O

O SO3Na

Irgacure -SONa Yes Yes a

N
O

O O
O
Irgacure  No Yes 

O
OH
b HO
Irgacure  Yes Yes -

(continued)
Chapter 2 New free radical and cationic photoinitiators for two-photon 3D printing
71
Table 2.4 (continued)
72

TPIs Water soluble Commercial δ nm (GM) Chemical structure

I I
O O O

I I
Rose Bengal Yes Yes  O 2K+
Cl
O

Cl Cl
Cl

Br Br
Shixiong Chen, Ruchun Zhou, Ming Jin

O O O

Eosin Y Yes Yes  Br Br

O

I I
O O ONa

Erythrosin Yes Yes  I I

O

ONa
 H
O N NH

N
N OH OH

Flavin adenine dinucleotide (FAD) Yes Yes . N O

H 2N
O P O
OH O
P O O N N
O
O
N N
HO H
OH

N
Methylene bule Yes Yes -b
N S N
Cl

(+I3NC6H12)2N
WSPI Yes No 
4I–
N(C6H12NI3+)2

GCK Yes No  O

O
N N O
O 2Na+

O
LAP Yes Yes -b
P
Chapter 2 New free radical and cationic photoinitiators for two-photon 3D printing

O
O Na+

a
Based on Irgacure 369
b
73

not known
 +
74

N (H2C) O
6 N O
+ (CH2) N+
N (H2C)
6 6 O O
N +
(CH2) N + – –+
O Na O N N ONa
6
4I–
P2CK
WSPI

O
O
+ – –+ O
Na O () () O Na HO
N N n
n OH
O O
Shixiong Chen, Ruchun Zhou, Ming Jin

G2CK n=1 Irgacure 2959

E2CK n=2

Scheme 2.6: The structures of TPIs in Li’s work.

 Chapter 2 New free radical and cationic photoinitiators for two-photon 3D printing 75

100

(c)
90

red
80
70
60

structure qualities
speed [mm/s]

(b)
P2CK

50

yellow
40
30

(a)
20
10

green
1
410

360

310

260

210

160

110

(B)
60
0

power [mW]

100
100

90
90

80
80

70
70

60
60

Speed [mm/s]
speed [mm/s]

G2CK
E2CK

50
50

40
40

30
30

20
20

10
10

1
1
410

360

310

260

210

160

110

410

360

310

260

210

160

110
60

60
0

power [mW] power [mW]

(A)

Figure 2.16: (a) Processing windows of investigated initiators in TPP screening tests;
(b) Classification of the structures by the typical quality of their shapes. Reproduced
with permission from [57]. Copyright 2013, Royal Society of Chemistry.
 76

Scheme 2.7: The structures of TPIs in Huang’s work.

Shixiong Chen, Ruchun Zhou, Ming Jin
 Chapter 2 New free radical and cationic photoinitiators for two-photon 3D printing 77

(a) (b)

6um

3um

Incident energy (mW) 3D carbon nano-tube

(c)

Figure 2.17: (a) 2D micropattern fabricated by changing the incident energy with a fixed line scan
speed of 10 μm/s; (b) 3D carbon nano-tube fabricated with 0.72 mW power and 110 μm/s scan
speed; (c) 2D logo of our laboratory, the designed model (left) and real pattern (right). Reproduced
with permission from [58]. Copyright 2017, Elsevier.

inorganic salts that can be reduced) by means of intermolecular electron transfer

followed by the generation of acid and the cationic polymerization.
The dyes with dipolar, quadrupolar or octupolar push-pull systems are the most
common sensitizers in two-photon polymerization initiation systems. In 2019, Jia and
his coworkers synthesized a series of quadrupolar A-π-D-π-A molecules [65], of which
the δmax is in the range of 285–1,030GM, as is shown in Figure 2.22(a) and Table 2.7.
The fabrication thresholds of P-DSO and T-DSO at 780 nm are 4.11 mW and 4.55 mW,
respectively (speed: 10 μm s−1). A two-layer periodic microstructure was produced
with a laser power of 10.1 mW and a writing speed of 100 μm s−1, as is shown in
Figure 2.22(b). The distance between every two neighboring polymerization streaks
(∼380 nm) is about 1.7 μm and the unpolymerized resin can be easily washed out by
ethanol.
Duocastella and his coworkers [66] found that the fullerene derivative, [6,6]-
phenyl-C61-butyric acid methyl ester (C60-PCBM, shown in Figure 2.5(a)) can initiate
the cationic polymerization together with AgPF6. The δ of PCBM is approximately
400GM, which is comparable to that of fullerene derivates. In the PCBM/AgPF6
78 Shixiong Chen, Ruchun Zhou, Ming Jin

Figure 2.18: (a) Logo of TIPC, (b) a gear structure and (c) a carbon nanotube structure, fabricated
with 4.88 mW power and 110 μm s−1 scan speed. Reproduced with permission from [59]. Copyright
2019, Royal Society of Chemistry.

(a) ⊕ (b)
⊕N Laser power decreasing
N
⊝ ⊝
I I 10.5 10.0 9.5 9.1 8.7 8.2 7.8 7.2 6.9mW

280nm 180nm
N
Laser power decreasing Threshold

6.5 6.2 5.9 5.7 5.5 5.2 5.0 4.7 4.5mW

2μm
unit: mW
BMVPC
(c)
300
Line width (nm)

270
O
H 240
N N C
H H H
210
H
N N 180
H 7
O 150
7 8 9 10 11 12 13 14
Cucurbit[7]uril (CB7)
Laser power (mW)

Figure 2.19: (a) Structures of BMVPC and CB7; (b) SEM images of hydrogel nanowire array
fabricated with varied laser power from 10.5 to 4.5 mW at a scanning speed of 10 μm s–1.
(c) Corresponding dependence of the linewidth on the laser power. Reproduced with permission
from [60]. Copyright 2019, American Chemistry Society.

system, the ground-state complex can be formed and the Ag+ will be reduced to Ag0
when PCBM is in the singlet excited state, forming the PCBM+·/Ag0. The cationic
polymerization will then be initiated. Interestingly, the electron transfer of PCBM/
Ag+ is revisable. The radical cation (PCBM+·) disappeared in the nanosecond time
scale, returning to PCBM (shown in Figure 2.23(a)). Thus, the active species formed
in the TPP process decreased; the “memory effect” was significantly limited. The
 Chapter 2 New free radical and cationic photoinitiators for two-photon 3D printing 79

Table 2.5: Summary of photophysical properties of TPIs in Zheng’s work.

TPIs solvent λmax/nma δ/GMb

BMVPC HO  

BMVPC DMSO  
BMVPC+CB (eq.) HO  ,
BMVPC+CB (eq.) HO  ,
a
one-photon absorption
b
measured by two-photon excited fluorescence

Figure 2.20: (a) The molecular structure of PAG-1 to PAG-4. (b) The SEM image of a microstructure
fabricated upon excitation at 780 nm (Power is 15 mW, speed is 5 μm s−1). Formulation: SU-8 resin with
PAG-3 (1 wt%). Reproduced with permission from [63]. Copyright 2015, Royal Society of Chemistry.
80 Shixiong Chen, Ruchun Zhou, Ming Jin

Figure 2.21: (a) The molecular structure of PAG-5 to PAG-8. (b) The microscopy image of a
microstructure fabricated upon excitation at 780 nm (Power is 10 mW, speed is 5 μm s−1).
Formulation: SU-8 resin with Bi-Meta (1 wt%). Scale bars: 5 mm. Reproduced with permission from
[64]. Copyright 2016, Elsevier.

Table 2.6: The linear and nonlinear photophysical properties and acid generation property of PAGs
in Figures 2.20 and 2.21.

PAGs λmax/nma ελmax/L mol− cm−a δ nm/GMb ΦH+

PAG-  ,  .

PAG-  ,  .
PAG-  ,  .
PAG-  ,  .
PAG-  ,  .
PAG-  ,  .
PAG-  ,  .
PAG-  ,  .
a
linear absorption spectra in ACN
Open aperture Z-scan measurement, the uncertainty of δ is in the order of 20%
b
 Chapter 2 New free radical and cationic photoinitiators for two-photon 3D printing 81

Figure 2.22: (a) The molecular structure of A-π-D-π-A synthesized by Jia. (b) SEM images of 3D
microstructures fabricated by TPP with a writing speed of 100 μm s−1, P-DSO/iodonium salt (0.1%/
1%, w/w), P = 10.1 mW. Reproduced with permission from [65]. Copyright 2019, Royal Society of
Chemistry.

Table 2.7: The linear and nonlinear photophysical properties and acid generation property of PAGs
in Figure 2.22(a).

Dyes λmax/nma ελmax/L mol− cm−a δ nm/GMb δmax/GMb

C-DSO  ,  

P-DSO  ,  ,
T-DSO  ,  ,
a
linear absorption spectra in ACN
b
Two-photon excited fluorescence measurement

polymerization profit of the PCBM/AgPF6 initiation system is merely the same as

that of ITX/commercial sulfonium salt (shown in Figure 2.23(c–d)). However, the
spatial resolution of nano-scale 3D structure increases (shown in Figure 2.23(e–f)).
82 Shixiong Chen, Ruchun Zhou, Ming Jin

Figure 2.23: (a) The molecular structure of C60-PCBM; (b) Schematic energy level diagrams together
with the proposed decay pathways for PCBM/AgPF6 upon excitation at 400 nm; SEM images of the
photopolymerized lines fabricated via DLW lithography (c) with the conventional sulfonium salt and
ITX at 85 mW and (d) with PCBM/AgPF6 as the cationic photoinitiator at 95 mW. Scale bar = 3 μm;
Height profiles of the photopolymerized lines using the (e) conventional sulfonium salt and ITX and
the (f) PCBM/AgPF6 system at different theoretical separation between the lines: 750, 600, 500, 400,
and 300 nm. Reproduced with permission from [66]. Copyright 2017, American Chemical Society.
 Chapter 2 New free radical and cationic photoinitiators for two-photon 3D printing 83

2.5 Some application based on 3D printing

and microfabrication
2.5.1 Biological

Paun and his coworkers [67] prepared the 3D honeycomb-like structures (HSs) by
using 7-(Diethylamino)-3-(2-thienylcarbonyl)-2H-1-benzopyran 2-one as a water-
soluble two-photon photoinitiator. As is shown in Figure 2.24, fabrication using
Laser direct writing (LDW) by the TPP of such complex structures with isotropic
and reproducible architectures is feasible. Importantly, LDW by TPP overcomes the
major disadvantages of randomness and loss of isotropy on entire volume encoun-
tered for previously reported HSs. The newly designed and prepared HSs ensured

Figure 2.24: 3D structure produced by LDW via TPP in IP-L780 photopolymer: (a) large area
overview; (b) side view of the structure tilted at 30°; (c) top view of the structure; (d) closer top
views of the structure with dimensions. Laser power was 25 mWand scan speed 50 μm s−1 for all
structures. Reproduced with permission from [67]. Copyright 2018, IOP Publishing.
84 Shixiong Chen, Ruchun Zhou, Ming Jin

the possibility to control the 3D spatial cells growth inside complex 3D honeycomb-
like architectures by adjusting the free spacing inside the structures. These 3D
structures supported viable and functioning human osteoblasts and have a real
potential as orthopedic implants.
Accardo and his coworkers [68] fabricated 3D freestanding scaffolds, which
was achieved by multiphoton DLW and seeded with neuroblastoma cells, as is
shown in Figure 2.25. The high accuracy of the fabrication process (about 200 nm)
allows a much finer control of the micro- and nanoscale features compared to other
3D printing technologies that are based on fused deposition modeling, inkjet print-
ing, selective laser sintering, or polyjet technology. Both SEM morphological inves-
tigation and confocal imaging showed a high level of cell adhesion as well as the
capability to form long and thick neuritic extensions (up to ≈ 60 µm). This work
opens interesting scenarios for the use of 3D fabrication/3D imaging protocols in
several neuroscientific contexts.
Versace and his coworkers [69] prepared the μ-cage with highly virulent bacte-
ricidal effect by using curcumin as two-photon initiator, as is shown in Figure 2.26
(a–d). The height of μ-cage (4.1 ± 0.4 μm) is four times higher than the feature size
of Staphylococcus aureus (S. aureus) so that the bacteria can be easily trapped. The
amount of curcumin is large (4% wt in monomer PETIA) that most of them can be
embedded in the microstructure, which will generate H2O2 after the irradiation of
visible light to kill the S. aureus bacteria. As is shown in Figure 2.26, such μ-cages
exhibit very impressive photocytotoxicity with a bacteria mortality rate of 95%,
after only 10 m of irradiation.
Wei et al. [70] reported bovine serum albumin (BSA)-based three-dimensional
microstructures with tunable surface morphology and pH-responsive properties via
TPP microfabrication technology. The tunable morphology of BSA microstructures
and a wide range of pH responses corresponding to the swelling ratio of 1.08–2.71
have been achieved. The swelling behavior of the microstructures can be strongly
influenced by the concentration of BSA precursor. A panda facial micropattern with
unique facial expression changes and mesh microsieve structures with changing
pore sizes in different pH values were fabricated, as is shown in Figure 2.27. Due to
the wild range of pH responses, it is a promising application in drug delivery.

2.5.2 Composite materials

Shota Ushiba and his coworkers [71] prepared the single wall carbon nanotube
(SWCNT) reinforced composite materials by TPP. By using 2-Benzyl-2-(dimethyla-
mino)-4ʹ-morpholinobutyrophenone as the photosensitizer, the SWCNT containing
photosensitive resin can be irradiated by femtosecond pulsed laser (780 nm) to fab-
ricate the micro/nano scaled composite materials, as is shown in Figure 2.28.
Figure 2.25: (a) CAD design of the 3D scaffold; (b) SEM micrograph of the 3D scaffold; (c) close‐up on the micrometer‐scaled cylindrical subunits of the
CAD design; (d) close‐up on the micro‐ and nanoscale features of the 3D scaffold; (e) Light sheet fluorescence microscopy imaging of the 3D scaffold
seeded with N2A cells; (f) imaging of the inner part of the 3D scaffold from its back‐side. Reproduced with permission from [68]. Copyright 2017, John
Wiley and Sons.
Chapter 2 New free radical and cationic photoinitiators for two-photon 3D printing
85
86 Shixiong Chen, Ruchun Zhou, Ming Jin

Figure 2.26: (a) SEM of a 290 × 290 μm grid composed of periodic 30 × 30 μm square cages
fabricated by TPP (λirr: 800 nm, Eirr = 20 μJ). (b) 45° tilted view. (c) Fluorescence image of the two-
photon patterned microgrid. (d) Recorded fluorescence spectrum of embedded curcumin within the
grid. (e) Electro-Induced Reduction Mechanism of curcumin in the Presence of O2 Leading
Ultimately to the Formation of H2O2. (f) The steps for μ-cage to kill S. aureus bacteria. Reproduced
with permission from [69]. Copyright 2020, American Chemistry Society.
 Chapter 2 New free radical and cationic photoinitiators for two-photon 3D printing 87

Figure 2.27: Preparation process of pH-responsive panda facial micropattern and the
microstructure at different pH. Reproduced with permission from [70]. Copyright 2017, American
Chemistry Society.

Figure 2.28: 3D micro/nano structural SWCNT/polymer composites are fabricated by using the TPP
lithography. The structures in (a)-(f) are an 8-μm-long micro bull, a micro tea pod, a micro lizard, a
nanowire suspended between two micro boxes, magnified image of (d), and perspective view of the
nanowire, respectively. Reproduced with permission from [71]. Copyright 2013, Elsevier.

Anne and his coworkers [72] prepared the microceramics by two-photon fabri-
cation and pyrolysis. In their work, Si-O-Ti-O networks were formed by the sol-gel
reaction and then the hybrid material was prepared by TPP using 4.4-Bis(dimethy-
lamino)benzophenone (photoinitiator a in Figure 2.29) and N-methylnifedipine
 88
Shixiong Chen, Ruchun Zhou, Ming Jin

Figure 2.29: Preparation process of Si-Ti microceramic. Photoinitiator a: Bis(dimethylamino)benzophenone; Photoinitiator b: N-methylnifedipine
ethyl ester derivative. Reproduced with permission from [72]. Copyright 2020, SpringerLink.
 Chapter 2 New free radical and cationic photoinitiators for two-photon 3D printing 89

ethyl ester derivative (photoinitiator b in Figure 2.29) as initiation systems. The mi-
croceramics were fabricated after the pyrolysis of hybrid materials, as is shown
in Figure 2.29.
Xiong et al. developed a soft magnetic hydrogel containing about 1% Fe3O4
nano particles (NPs) that acted as a magnetic actuator [73]. 2-benyl-2-(dimethyla-
mino)-4ʹ-morpholinobutyrophenone was used as photosensitizers and the magnetic
composite particles was prepared by the irradiation of 780 nm lasers (pulse length
is 80 fs; repetition rate is 80 MHz). The structures they prepared were also charac-
terized by a very small feature size, with lines that were down to 110 nm in width,
as is shown in Figure 2.30.

2.5.3 Optical materials

Vyatskikh et al. [74] prepared the 3D dielectric photonic crystals by TPP. By using Ti-
containing acrylate as monomers, the 3D Ti-containing microstructure was prepared
first, followed by the pyrolysis in the air at 750 °C–900 °C, as is shown in Figure 2.31.
The refractive index of the material can reach 2.3.
Quantum dots (QDs) films or layers have been extensively used for various pho-
tonic and electronic applications over the recent decades. Peng et al. [75] reported
the preparation of structures obtained from QDs dispersions in pentaerythritol tet-
raacrylate (PETA), which exhibited a superior resolution: they ascribed this phe-
nomenon to a smaller voxel, which is generated upon the absorption of photons by
the filler, as is shown in Figure 2.32.
Mayer et al. [76] prepared a series of microstructures composed of a nonfluores-
cent 3D cross-grid scaffold and fluorescent markers by the TPP of acrylate monomers,
realized by an acrylate-based resist containing CdS/Se-based core-shell semiconduc-
tor quantum dots, arranged onto this scaffold at will, as is shown in Figure 2.33.
First, the 3D cross‐grid with walls for stabilization and holes for drainage as well as
alignment markers on the substrate is 3D‐printed out of a nonfluorescent photoresist.
Second, fluorescent markers are added to the 3D cross‐grid using a fluorescent photo-
resist. This step can be repeated many times using fluorescent photoresists with
different emission colors. Finally, the structure is planarized using exactly the
same polymer as the 3D cross‐grid. With characteristic optical properties and
stability toward photobleaching, these microstructures could lead to important
breakthroughs in the fields of communication photonics and security.
Lata et al. [77] prepared the photonic crystals by a single fabrication step using
DLW, as is shown in Figure 2.34. A strong contrast of the cross-polarized reflectance
of photonic crystals as a function of the in-plane orientation is observed in the
mid-infrared spectral range at λ ≈ 6.5 μm. Photonic crystals obliquely oriented with
respect to the direction of the input polarization show a strong reflectance. The cross-
 90
Shixiong Chen, Ruchun Zhou, Ming Jin

Figure 2.30: Lines produced using photoresists with various contents of Fe3O4 NPs: (a–c) 0, (d–f) 0.32 wt%, and (g–i) 0.96 wt%. The magnified SEM
images of line 7, 8 (b), line 1, 2 (c), line 7, 8 (e), line 1, 2 (f), line 8, 9 (g), and line 2, 3 (h) come from the selected areas shown in (a), (d) and (g),
respectively. Scale bars = 1 μm; Magnetic-field driven hydrogel micro-rod: microscopy images of the micro-rod at (j) its original position and (k, l)
deflected positions, along with the corresponding (m) SEM image. θ is the deflecting angle between the original position of a micro-rod and a deflected
condition. Reproduced with permission from [73]. Copyright 2018, Elsevier.
 Chapter 2 New free radical and cationic photoinitiators for two-photon 3D printing 91

Figure 2.31: Process for nanoscale additive manufacturing (AM) of titanium dioxide and SEM
characterization of as-fabricated TiO2 3D architectures. (a) Ligand exchange reaction between
titanium (IV) ethoxide and acrylic acid is used to synthesize a liquid TiO2 precursor in the
photopolymer. (b) Titania preceramic photopolymer is used in a two-photon lithography process to
fabricate preceramic 3D architectures. (c) Schematic of a preceramic woodpile architecture
supported by a set of springs that decouple it from the substrate. (d) Titania woodpile structure is
formed by calcination of the preceramic part. (e, g) Representative SEM images of preceramic
woodpile architectures. (f–i) Representative TiO2 woodpile architectures after calcination at
750–900 °C. Scale bars are 50 μm for panel E, 20 μm for F, 2 μm for G, 1 μm for H, and 2 μm for
I. Reproduced with permission from [74]. Copyright 2020, American Chemistry Society.

polarized reflectance of the crystals that are perpendicularly or parallelly oriented to

the input polarization is vanishing.

2.5.4 Lithography

Bertin et al. [78] have developed an armed microbubble (AMB)‐based microswimmer,

shown in Figure 2.35. The shell‐shape structure was first fabricated on a glass sub-
strate by TPP. It was then placed in a polydimethylsiloxane chamber filled with
 92
Shixiong Chen, Ruchun Zhou, Ming Jin

Figure 2.32: SEM images of woodpile fabricated by TPP in a period of 350 nm fabricated by TPP in the formulation without QDs (a, b) and in the
presence of QDs‐R (c, d). The woodpile in a period of 500 nm, fabricated in the absence of QDs (e, f) and in a period of 400 nm, fabricated in the
presence of QDs‐R (g, h). Fabrication laser power: 8 mW; scanning speed: 100 µm s−1. Reproduced with permission from [75]. Copyright 2019,
John Wiley and Sons.
Figure 2.33: (a) Blueprint of the 3D‐printed fluorescent security feature (before embedding in a thin transparent polymer film).
It consists of fluorescent markers (green and blue) arranged onto a nonfluorescent 3D cross‐grid. (b) Scheme of the fabrication
process. Fluorescent readout of 3D security features measured by confocal laser scanning fluorescence microscopy. (c) 3D
reconstruction of the fluorescent markers results from the nonfluorescent support structure. (d) The structure based on two
Chapter 2 New free radical and cationic photoinitiators for two-photon 3D printing

fluorescent photoresists with different emission wavelengths. (e) Individual z‐slices of the 3D image stack shown in (c). The z‐
slice at the very left bottom corresponds to the substrate layer, the one in the top right to the uppermost marker layer. The
intensity normalization is relative to the peak slice intensity In of the individual sample. (f) Same as (e), but for the sample in
93

(c). Reproduced with permission from [76]. Copyright 2017, John Wiley and Sons.
94 Shixiong Chen, Ruchun Zhou, Ming Jin

Figure 2.34: (a) Tilted (approx. 50°) top-view SEM micrograph of fabricated birefringent photonic
crystals. The individual photonic crystals with azimuthal orientations ranging from 0° to 135° are
clearly distinguishable. The scale bars indicate 20 and 5 μm for the top panel and the insets,
respectively. (b) Cross-polarized reflectance image of the fabricated birefringent photonic crystals
obtained at normal incidence and λ ≈ 6.5 μm. The dotted boxes illustrate the surface area of the
individual photonic crystals with an azimuthal orientation from φ = 0° to 135° with respect to the
incident polarization direction. The scale bar indicates 20 μm. Reproduced with permission from
[77]. Copyright 2019, American Vacuum Society.

tracing particles. It is found that the bubble, protected by such a shell‐shaped struc-
ture, can last hours, which circumvents the problems of short lifetime for conven-
tional bubble‐based actuation. Later, free‐standing microswimmers were designed
and fabricated, and they were able to move with a speed of 1 mm s−1.
 Chapter 2 New free radical and cationic photoinitiators for two-photon 3D printing 95

Figure 2.35: (a) Spinner design; (b) fabricated spinner (SEM image); (c) armed microbubble (AMB)
spinning at 175 Hz under actuation with acoustic pressure (Pac) of 96.2 kPa; (d) AMB and pedestal;
(e) moving AMB with Pac = 5.6 kPa. Reproduced with permission from [78]. Copyright 2015,
American Physical Society.

Liao and his coworkers [79] prepared a series of functional three-dimensional (3D)
microstructures incorporating accessible interiors by TPP using IP-series resists (IP-L,
IP-S and IP-Dip), as is shown in Figure 2.36. Unlike conventional fabrication techni-
ques, the DLW-TPP fabrication scheme provides superior control over the full geomet-
ric properties (both interior and exterior) of the fabricated device. The tailored hollow
3D microstructure devices produced by our technique hold great potential for biosys-
tem applications, including micropores for biochemical sensing, microneedles for phar-
maceutical delivery, microelectrodes for neural recording, microvalves for biofluidic
measurement and manipulation and micromachines for biomedical therapy.
Dong and his coworkers [80] prepared a doubly re-entrant micropillar by DLW
using two-photon sensitive commercial photoresist, which is used for the formation
of superoleophobic slippery lubricant-infused surfaces, as is shown in Figure 2.37.
This novel type of slippery superoleophobic surface could be interesting for both fun-
damental research and practical applications, including superoleophobic surfaces
with extreme liquid repellency, controlled droplet mobility, anti-icing, anti-fouling,
anti-adhesive or other properties attributed to its lubricant-air hybrid interface.
96 Shixiong Chen, Ruchun Zhou, Ming Jin

Figure 2.36: Series of CAD-designed hollow 3D microdevices were fabricated using the TPP-enabled
DLW technique. Scale bar: 50 μm. (a, b) Hollow microneedles for enhanced pharmaceutical delivery.
Left: Tilt angle view. Right: Cross-section view. (c) Hollow microelectrode for neural recording and
stimulation. Left: Tilt angle view. Right: Cross-section view. (d) Hollow microvalve for biofluidic
controlling. Left: Tilt angle view. Right: Cross-section view. (e) Hollow microrobot for medical therapy.
Left: Tilt angle view. Right: Cross-section view. Reproduced with permission from [79]. Copyright 2019,
American Chemical Society (article link https://pubs.acs.org/doi/10.1021/acsomega.8b03164).

Power et al. [81] prepared a tethered, 3D, compliant grasper with an integrated
force sensor, the entirety of which is fabricated on the tip of an optical fiber in a
single‐step process using TPP, as is shown in Figure 2.38. The preparation process
is simple and the force error is small (Figures 2.38(e-f)), which holds significant po-
tential for future use in cellular manipulation, sensing, and microscale surgery.
Geng et al. [35] designed a revolutionary laser nanofabrication process based on
TPP and an ultrafast random-access digital micromirror device (DMD) scanner, as
is shown in Figure 2.39. By exploiting binary holography, the DMD scanner can si-
multaneously generate and individually control one to tens of laser foci for parallel
nano-fabrication at 22.7 kHz. Complex 3D trusses and woodpile structures have been
fabricated via single or multi-focus processes, showing a resolution of ~ 500nm. The
nanofabrication system may be used for largescale nano-prototyping or creation of
complex structures that cannot be easily fabricated via conventional raster-scanning-
based systems, bringing significant impact to the world of nanomanufacturing. The
functional 3D nanoprinting technique via two-photon lithography is demonstrated in
Chapter 8.
 Chapter 2 New free radical and cationic photoinitiators for two-photon 3D printing 97

Figure 2.37: SEM images of doubly re-entrant micropillars with flat and nanopillared (nanorough)
tops. (a) 45° view of doubly re-entrant micropillars with flat tops. The inset picture shows a 6 µL
ethanol drop deposited on a surface composed of the doubly re‐entrant micropillars with static
contact angle of 158 ± 5°. (b) 45° view of doubly re‐entrant micropillars with nanorough tops.
(c) Cross‐sectional view of a doubly re‐entrant micropillar with a nanorough top. Key geometric
parameters: D, P, and H are the diameter, pitch (center‐to‐center), and height of the doubly
re‐entrant micropillars, respectively. δ and t are the length and thickness of the vertical overhang,
respectively. d, p, and h are the diameter, pitch (center‐to‐center), and height of the nanopillars,
respectively. D = 25 µm, P = 100 µm, H = 50 µm, δ = 4.0 µm, t = 250 nm, d = 400 nm, p = 750 nm,
h = 1.0 µm. Reproduced with permission from [80]. Copyright 2018, John Wiley and Sons.
 98
Shixiong Chen, Ruchun Zhou, Ming Jin

Figure 2.38: (a) CAD model of the gripper with a side‐on view of one of the three gripper fingers. The compressible three‐hinge mechanism is
highlighted in red, along with the locations of the three flexure hinges. (b) An illustration of the printing setup in the TPP system. The optical fiber is
suspended with the cleaved surface facing downward toward the focal point of the TPP system. (c) An SEM image of the full gripper fabricated on the tip
of a 125 µm diameter optical fiber. The link lengths of the compressible three‐hinge mechanism are annotated. (d) A zoomed‐in view of the microgripper
force‐sensing element. The thin, semi‐transparent plates are colored yellow, with the plate thickness and spacing annotated. (e) 7.5 m of applied versus
predicted force from a manual control validation experiment. The average predicted force error is 0.8 µN. (f) 4 m of applied versus predict force from an
automated control validation experiment, where the setpoint force was 17 µN. The average predicted force error is 0.8 µN. Reproduced with permission
from [81]. Copyright 2018, John Wiley and Sons.
Figure 2.39: (a) Optical configuration of the TPP fabrication system. Femtosecond laser beams are scanned by the DMD
multi-point random-access scanner. M1, high-reflectivity mirrors; DM, dichroic mirror; BS, beam splitter; L1–L4: lenses (fL1,
fL2, fL3, fL4 = 100, 250, 200, 200 mm, respectively); (b) CAD model of the microscale London Bridge; (c) SEM image of the TPP
Chapter 2 New free radical and cationic photoinitiators for two-photon 3D printing

fabricated London Bridge. Scale bar: 10 μm; single-focus, two-focus, and three-focus fabrication results. (d–f) Planned laser
scanning trajectories; (g–i) snapshots of the multi-focus TPP fabrication process; (j–l) SEM images of the fabricated
woodpile structures. Scale bars: 10 μm. Reproduced with permission from [35]. Copyright 2019, Springer Nature.
99
100 Shixiong Chen, Ruchun Zhou, Ming Jin

2.6 Conclusions and perspectives

As one of the most popular processing methods, 3D printing by TPP has already
shown its advantages in the microfabrication. For the TPP system, the initiation sys-
tem with good TPA is still the focus of research. Initiators or sensitizers with multi-
ple functions can simplify the chemical environment of the formulation and
facilitate research on the initiation ability of the photoinitiator system, which will
also become a focus area. At the same time, with the widespread application of ce-
ramic matrix composites, the use of two-photon polymerization to prepare hybrid
materials that will form the ceramic material after the pyrolysis will become a new
method for ceramic matrix microstructure preparation. Besides, the high spatial se-
lectivity may lead the TPP to the application of microcircuit lithography. The photo-
initiation system with high two-photon absorption cross section combined with a
suitable monomer, resin and other functional additives, has a promising applica-
tion in many advanced research fields.

References
[1] Göppert-Mayer, M. Über elementarakte mit zwei quantensprüngen, Ann Phys (Berlin Ger),
1931, 401, 273–294.
[2] Kaiser, W. K., Garrett, C. G. B. Two-photon excitation in CaF2: Eu2+, Phys Rev Lett, 1961, 7,
229–231.
[3] Rapp, W., Gronau, B. Laser emission from two xanthene dyes via double-photon excitation,
Chem Rev Lett, 1971, 8, 529–532.
[4] Rubinov, A. N., Richardson, M. C., Sala, K., Alcock, A. J. Generation of single-picosecond dye
laser pulses using one- and two-photon traveling-wave excitation, Appl Phys Lett, 1975, 27,
358–360.
[5] Qiu, P., Penzkofer, A. Intense ultrashort pulse generation in a 2-photon pumped generator-
amplifier system, Appl Phys B: Photophys Laser Chem, 1989, 48, 115–124.
[6] Bhawalkar, J. D., He, G. S., Prasad, P. N. Nonlinear multiphoton processes in organic and
polymeric materials, Rep Prog Phys, 1996, 59, 1041–1070.
[7] Lim, C. S., Cho, B. R. Two-photon probes for biomedical applications, BMB Rep, 2013, 46,
188–194.
[8] Kim, D., Ryu, H. G., Ahn, K. H. Recent development of two-photon fluorescent probes for
bioimaging, Org Biomol Chem, 2014, 12, 4550–4566.
[9] Gan, X., Wang, Y., Ge, X., Li, W., Zhang, X., Zhu, W., Zhou, H., Wu, J., Tian, Y. Triphenylamine
isophorone derivatives with two photon absorption: Photo-physical property, DFT study and
bio-imaging, Dye Pigm, 2015, 120, 65–73.
[10] Wu, P.-C., Wang, J.-Y., Wang, W.-L., Chang, C.-Y., Huang, C.-H., Yang, K.-L., Chang, J.-C., Hsu,
C.-L.-L., Chen, S.-Y., Chou, T.-M., Kuo, W.-S. Efficient two-photon luminescence for cellular
imaging using biocompatible nitrogen-doped graphene quantum dots conjugated with
polymers, Nanoscale, 2018, 10, 109–117.
[11] Caminade, A.-M., Zibarov, A., Diaz, E. C., Hameau, A., Klausen, M., Ching, K. M.-C., Majoral,
J.-P., Verlhac, J.-B., Mongin, O., Blanchard-Desce, M. Fluorescent phosphorus dendrimers
 Chapter 2 New free radical and cationic photoinitiators for two-photon 3D printing 101

excited by two photons: Synthesis, two-photon absorption properties and biological uses,
Beilstein J Org Chem, 2019, 15, 2287–2303.
[12] D’Aleo, A., Bourdolle, A., Brustlein, S., Fauquier, T., Grichine, A., Duperray, A., Baldeck, P. L.,
Andraud, C., Brasselet, S., Maury, O. Ytterbium-based bioprobes for near-infrared two-photon
scanning laser microscopy imaging, Angew Chem Int Ed Engl, 2012, 51, 6622–6625.
[13] Zhang, P., Wang, J., Huang, H., Chen, H., Guan, R., Chen, Y., Ji, L., Chao, H. RuNH2@AuNPs as
two-photon luminescent probes for thiols in living cells and tissues, Biomaterials, 2014, 35,
9003–9011.
[14] Jin, F., Pan, C., Zhang, W., Sun, L., Hu, X., Liao, R., Tao, D. Enhanced two-photon excited
fluorescence of mercury complexes with a conjugated ligand: Effect of the central metal ion, J
Lumin, 2016, 172, 264–269.
[15] Park, Y. I., Lee, K. T., Suh, Y. D., Hyeon, T. Upconverting nanoparticles: A versatile platform
for wide-field two-photon microscopy and multi-modal in vivo imaging, Chem Soc Rev, 2015,
44, 1302–1317.
[16] Ke, M.-T., Fujimoto, S., Imai, T. SeeDB: A simple and morphology-preserving optical clearing
agent for neuronal circuit reconstruction, Nat Neurosci, 2013, 16, 1154–U246.
[17] Yang, W., Yuste, R. In vivo imaging of neural activity, Nat Methods, 2017, 14, 349–359.
[18] Wang, X., Wei, Z., Baysah, C. Z., Zheng, M., Xing, J. Biomaterial-based microstructures
fabricated by two-photon polymerization microfabrication technology, RSC Adv, 2019, 9,
34472–34480.
[19] Lin, Y., Xu, J. Microstructures fabricated by two-photon polymerization and their remote
manipulation techniques: Toward 3D printing of micromachines, Adv Opt Mater, 2018, 6,
1701359.
[20] LaFratta, C. N., Baldacchini, T. Two-photon polymerization metrology: Characterization
methods of mechanisms and microstructures, Micromachines, 2017, 8, 101.
[21] Ogawa, K. Two-photon absorbing molecules as potential materials for 3D optical memory,
Appl Sci (Basel, Switz), 2014, 4, 1–18.
[22] Chu, Y., Xiao, H., Wang, G., Xiang, J., Fan, H., Liu, H., Wei, Z., Tie, S., Lan, S., Dai,
Q. Randomly distributed plasmonic hot spots for multilevel optical storage, J Phys Chem C,
2018, 122, 15652–15658.
[23] Lemercier, G., Four, M., Chevreux, S. Two-photon absorption properties of 1,10-
phenanthroline-based Ru(II) complexes and related functionalized nanoparticles for potential
application in two-photon excitation photodynamic therapy and optical power limiting, Coord
Chem Rev, 2018, 368, 1–12.
[24] Medishetty, R., Zareba, J. K., Mayer, D., Samoc, M., Fischer, R. A. Nonlinear optical
properties, upconversion and lasing in metal-organic frameworks, Chem Soc Rev, 2017, 46,
4976–5004.
[25] Liu, Z., Hu, Z., Shi, T., Du, J., Yang, J., Zhang, Z., Tang, X., Leng, Y. Stable and enhanced
frequency up-converted lasing from CsPbBr3 quantum dots embedded in silica sphere, Opt
Express, 2019, 27, 9459–9466.
[26] Paisley, N. R., Tonge, C. M., Mayder, D. M., Thompson, K. A., Hudson, Z. M. Tunable
benzothiadiazole-based donor-acceptor materials for two-photon excited fluorescence, Mater
Chem Front, 2020, 4, 555–566.
[27] McKenzie, L. K., Bryant, H. E., Weinstein, J. A. Transition metal complexes as photosensitisers
in one- and two-photon photodynamic therapy, Coord Chem Rev, 2019, 379, 2–29.
[28] Griesbeck, S., Michail, E., Wang, C., Ogasawara, H., Lorenzen, S., Gerstner, L., Zang, T.,
Nitsch, J., Sato, Y., Bertermann, R., Taki, M., Lambert, C., Yamaguchi, S., Marder, T. B. Tuning
the π-bridge of quadrupolar triarylborane chromophores for one- and two-photon excited
fluorescence imaging of lysosomes in live cells, Chem Sci, 2019, 10, 5405–5422.
102 Shixiong Chen, Ruchun Zhou, Ming Jin

[29] Guo, L., Wong, M. S. Multiphoton excited fluorescent materials for frequency upconversion
emission and fluorescent probes, Adv Mater, 2014, 26, 5400–5428.
[30] Fam, T. K., Klymchenko, A. S., Collot, M. Recent advances in fluorescent probes for lipid
droplets, Materials, 2018, 11, 1768.
[31] Kasko, A. M., Wong, D. Y. Two-photon lithography in the future of cell-based therapeutics and
regenerative medicine: A review of techniques for hydrogel patterning and controlled release,
Future Med Chem, 2010, 2, 1669–1680.
[32] Zhao, W., Zhao, Y., Wang, Q., Liu, T., Sun, J., Zhang, R. Remote light-responsive nanocarriers
for controlled drug delivery: Advances and perspectives, Small, 2019, 15.
[33] Schafer, K. J., Hales, J. M., Balu, M., Belfield, K. D., Van Stryland, E. W., Hagan, D. J. Two-
photon absorption cross-sections of common photoinitiators, J Photochem Photobiol A,
2004, 162, 497–502.
[34] Pawlicki, M., Collins, H. A., Denning, R. G., Anderson, H. L. Two-photon absorption and the
design of two-photon dyes, Angew Chem Int Ed Engl, 2009, 48, 3244–3266.
[35] Geng, Q., Wang, D., Chen, P., Chen, S.-C. Ultrafast multi-focus 3-D nano-fabrication based on
two-photon polymerization, Nat Commun, 2019, 10, 2179.
[36] Albota, M., Beljonne, D., Bredas, J. L., Ehrlich, J. E., Fu, J. Y., Heikal, A. A., Hess, S. E., Kogej,
T., Levin, M. D., Marder, S. R., McCord-Maughon, D., Perry, J. W., Rockel, H., Rumi, M.,
Subramaniam, C., Webb, W. W., Wu, X. L., Xu, C. Design of organic molecules with large two-
photon absorption cross sections, Science, 1998, 281, 1653–1656.
[37] Li, Z., Hu, P., Zhu, J., Gao, Y., Xiong, X., Liu, R. Conjugated carbazole-based schiff bases as
photoinitiators: From facile synthesis to efficient two-photon polymerization, J Polym Sci
Polym Chem, 2018, 56, 2692–2700.
[38] Qiu, W., Hu, P., Zhu, J., Liu, R., Li, Z., Hu, Z., Chen, Q., Dietliker, K., Liska, R. Cleavable
unimolecular photoinitiators based on oxime-ester chemistry for two-photon three-
dimensional printing, Chemphotochem, 2019, 3, 1090–1094.
[39] Cao, X., Jin, F., Li, Y.-F., Chen, W.-Q., Duan, X.-M., Yang, L.-M. Triphenylamine-modified
quinoxaline derivatives as two-photon photoinitiators, New J Chem, 2009, 33, 1578–1582.
[40] Pucher, N., Rosspeintner, A., Satzinger, V., Schmidt, V., Gescheidt, G., Stampfl, J., Liska,
R. Structure-activity relationship in D-π-A-π-D-based photoinitiators for the two-photon-
induced photopolymerization process, Macromolecules, 2009, 42, 6519–6528.
[41] Lu, W., Dong, X., Chen, W., Zhao, Z., Duan, X. Novel photoinitiator with a radical quenching
moiety for confining radical diffusion in two-photon induced photopolymerization, J Mater
Chem, 2011, 21, 5650–5659.
[42] Malval, J.-P., Jin, M., Morlet-Savary, F., Chaumeil, H., Defoin, A., Soppera, O., Scheul, T.,
Bouriau, M., Baldeck, P. L. Enhancement of the two-photon initiating efficiency of a
thioxanthone derivative through a chevron-shaped architecture, Chem Mater, 2011, 23,
3411–3420.
[43] Xue, J., Zhao, Y., Wu, H., Wu, F. Novel benzylidene cyclopentanone dyes for two-photon
photopolymerization, J Photochem Photobiol A, 2008, 195, 261–266.
[44] Fitilis, I., Fakis, M., Polyzos, I., Giannetas, V., Persephonis, P. Two-photon polymerization of a
diacrylate using fluorene photoinitiators-sensitizers, J Photochem Photobiol A, 2010, 215,
25–30.
[45] Li, Z., Siklos, M., Pucher, N., Cicha, K., Ajami, A., Husinsky, W., Rosspeintner, A., Vauthey, E.,
Gescheidt, G., Stampfl, J., Liska, R. Synthesis and structure-activity relationship of several
aromatic ketone-based two-photon initiators, J Polym Sci Polym Chem, 2011, 49, 3688–3699.
[46] Chi, T., Somers, P., Wilcox, D. A., Schuman, A. J., Iyer, V., Le, R., Gengler, J., Ferdinandus, M.,
Liebig, C., Pan, L., Xu, X., Boudouris, B. W. Tailored thioxanthone-based photoinitiators for
 Chapter 2 New free radical and cationic photoinitiators for two-photon 3D printing 103

two-photon-controllable polymerization and nanolithographic printing, J Polym Sci Polym

Phys, 2019, 57, 1462–1475.
[47] Hu, P., Zhu, J., Liu, R., Li, Z. Conjugated ketocarbazoles as efficient photoinitiators: From
facile synthesis to efficient two-photon polymerization, J Photopoly Sci Technol, 2019, 32,
257–264.
[48] Hu, P., Qiu, W., Naumov, S., Scherzer, T., Hu, Z., Chen, Q., Knolle, W., Li, Z. Conjugated
bifunctional carbazole-based oxime esters: Efficient and versatile photoinitiators for 3D
printing under one- and two-photon excitation, Chemphotochem, 2020, 4, 224–232.
[49] Poocza, L., Gottschaldt, M., Markweg, E., Hauptmann, N., Hildebrand, G., Pretzel, D.,
Hartlieb, M., Reichardt, C., Kuebel, J., Schubert, U. S., Mollenhauer, O., Dietzek, B., Liefeith,
K. Optimized photoinitiator for fast two-Photon absorption Polymerization of polyester-
macromers for tissue engineering, Adv Eng Mater, 2017, 19, 1600686.
[50] Zhou, R., Malval, J.-P., Jin, M., Spangenberg, A., Pan, H., Wan, D., Morlet-Savary, F., Knopf,
S. A two-photon active chevron-shaped type I photoinitiator designed for 3D
stereolithography, Chem Commun, 2019, 55, 6233–6236.
[51] Ovsianikov, A., Schlie, S., Ngezahayo, A., Haverich, A., Chichkov, B. N. Two-photon
polymerization technique for microfabrication of CAD-designed 3D scaffolds from
commercially available photosensitive materials, J Tissue Eng Regener Med, 2007, 1,
443–449.
[52] Klein, F., Striebel, T., Fischer, J., Jiang, Z., Franz, C. M., von Freymann, G., Wegener, M.,
Bastmeyer, M. Elastic fully three-dimensional microstructure scaffolds for cell force
measurements, Adv Mater, 2010, 22, 868–871.
[53] Ovsianikov, A., Malinauskas, M., Schlie, S., Chichkov, B., Gittard, S., Narayan, R.,
Loebler, M., Sternberg, K., Schmitz, K. P., Haverich, A. Three-dimensional laser micro- and
nano-structuring of acrylated poly(ethylene glycol) materials and evaluation of their
cytoxicity for tissue engineering applications, Acta Biomater, 2011, 7, 967–974.
[54] Ovsianikov, A., Gruene, M., Pflaum, M., Koch, L., Maiorana, F., Wilhelmi, M., Haverich, A.,
Chichkov, B. Laser printing of cells into 3D scaffolds, Biofabrication, 2010, 2, 1800522.
[55] Torgersen, J., Qin, X.-H., Li, Z., Ovsianikov, A., Liska, R., Stampfl, J. Hydrogels for two-photon
polymerization: A toolbox for mimicking the extracellular matrix, Adv Funct Mater, 2013, 23,
4542–4554.
[56] Song, J., Michas, C., Chen, C. S., White, A. E., Grinstaff, M. W. From simple to architecturally
complex hydrogel scaffolds for cell and tissue engineering applications: Opportunities
presented by two-photon polymerization, Adv Healthcare Mater, 2020, 9.
[57] Li, Z., Torgersen, J., Ajami, A., Muehleder, S., Qin, X., Husinsky, W., Holnthoner, W.,
Ovsianikov, A., Stampfl, J., Liska, R. Initiation efficiency and cytotoxicity of novel water-
soluble two-photon photoinitiators for direct 3D microfabrication of hydrogels, RSC Adv,
2013, 3, 15939–15946.
[58] Huang, X., Wang, X., Zhao, Y. Study on a series of water-soluble photoinitiators for
fabrication of 3D hydrogels by two-photon polymerization, Dye Pigm, 2017, 141, 413–419.
[59] Huang, X., Zhang, Y., Shi, M., Zhang, Y., Zhao, Y. Study on a polymerizable visible light
initiator for fabrication of biosafety materials, Polym Chem, 2019, 10, 2273–2281.
[60] Zheng, Y.-C., Zhao, -Y.-Y., Zheng, M.-L., Chen, S.-L., Liu, J., Jin, F., Dong, X.-Z., Zhao, Z.-S.,
Duan, X.-M. Cucurbit 7 uril-carbazole two-photon photoinitiators for the fabrication of
biocompatible three-dimensional hydrogel scaffolds by laser direct writing in aqueous
solutions, ACS Appl Mater Interfaces, 2019, 11, 1782–1789.
[61] Belfield, K. D., Schafer, K. J., Liu, Y. U., Liu, J., Ren, X. B., Van Stryland, E. W. Multiphoton-
absorbing organic materials for microfabrication, emerging optical applications and non-
destructive three-dimensional imaging, J Phys Org Chem, 2000, 13, 837–849.
104 Shixiong Chen, Ruchun Zhou, Ming Jin

[62] Zhou, W. H., Kuebler, S. M., Braun, K. L., Yu, T. Y., Cammack, J. K., Ober, C. K., Perry, J. W.,
Marder, S. R. An efficient two-photon-generated photoacid applied to positive-tone 3D
microfabrication, Science, 2002, 296, 1106–1109.
[63] Jin, M., Wu, X. Y., Xie, J. C., Malval, J. P., Wan, D. C. One/two-photon-sensitive photoacid
generators based on benzene oligomer-containing D-π-A-type aryl dialkylsulfonium salts,
RSC Adv, 2015, 5, 55340–55347.
[64] Wu, X., Jin, M., Xie, J., Malval, J. P., Wan, D. One/two-photon cationic polymerization in visible
and near infrared ranges using two-branched sulfonium salts as efficient photoacid
generators, Dye Pigm, 2016, 133, 363–371.
[65] Jia, X., Han, W., Xue, T., Zhao, D., Li, X., Nie, J., Wang, T. Diphenyl sulfone-based A–π-D–π-A
dyes as efficient initiators for one-photon and two-photon initiated polymerization, Polym
Chem, 2019, 10, 2152–2161.
[66] Duocastella, M., Vicidomini, G., Korobchevskaya, K., Pydzińska, K., Ziółek, M., Diaspro, A.,
Migue, G. D. Improving the spatial resolution in direct laser writing lithography by using a
reversible cationic photoinitiator, J Phys Chem C, 2017, 121, 16970–16977.
[67] Paun, I. A., Popescu, R. C., Mustaciosu, C. C., Zamfirescu, M., Calin, B. S., Mihailescu, M.,
Dinescu, M., Popescu, A., Chioibasu, D., Soproniy, M., Luculescu, C. R. Laser-direct writing by
two-photon polymerization of 3D honeycomb-like structures for bone regeneration,
Biofabrication, 2018, 10, 025009.
[68] Accardo, A., Blatche, M. C., Courson, R., Loubinoux, I., Thibault, C., Malaquin, L., Vieu,
C. Multiphoton direct laser writing and 3D imaging of polymeric freestanding architectures
for cell colonization, Small, 2017, 13, 1700621.
[69] Versace, D. L., Moran, G., Belqat, M., Spangenberg, A., Meallet-Renault, R., Abbad-
Andaloussi, S., Brezova, V., Malval, J. P. Highly virulent bactericidal effects of curcumin-
based μm-cages fabricated by two-photon polymerization, ACS Appl Mater Interfaces, 2020,
12, 5050–5057.
[70] Wei, S. X., Liu, J., Zhao, Y. Y., Zhang, T. B., Zheng, M. L., Jin, F., Dong, X. Z., Xing, J. F., Duan,
X. M. Protein-based 3D microstructures with controllable morphology and pH-responsive
properties, ACS Appl Mater Interfaces, 2017, 9, 42247–42257.
[71] Ushiba, S., Shoji, S., Masui, K., Kuray, P., Kono, J., Kawata, S. 3D microfabrication of single-
wall carbon nanotube/polymer composites by two-photon polymerization lithography,
Carbon, 2013, 59, 283–288.
[72] Desponds, A., Banyasz, A., Montagnac, G., Andraud, C., Baldeck, P., Parola,
S. Microfabrication by two-photon lithography, and characterization, of SiO2/TiO2 based
hybrid and ceramic microstructures, J Sol-Gel Sci Technol, 2020, 95, 733–745.
[73] Xiong, Z., Zheng, C., Jin, F., Wei, R., Zhao, Y., Gao, X., Xia, Y., Dong, X., Zheng, M., Duan,
X. Magnetic-field-driven ultra-small 3D hydrogel microstructures: Preparation of gel
photoresist and two-photon polymerization microfabrication, Sens Actuators B, 2018, 274,
541–550.
[74] Vyatskikh, A., Ng, R. C., Edwards, B., Briggs, R. M., Greer, J. R. Additive manufacturing of
high-refractive-index, nanoarchitected titanium dioxide for 3D dielectric photonic crystals,
Nano Lett, 2020, 20, 3513–3520.
[75] Peng, Y., Jradi, S., Yang, X., Dupont, M., Hamie, F., Xuan Quyen, D., Sun, X. W., Xu, T.,
Bachelot, R. 3D photoluminescent nanostructures containing quantum dots fabricated by
two-photon polymerization: Influence of quantum dots on the spatial resolution of laser
writing, Adv Mater Technol, 2019, 4, 1800522.
[76] Mayer, F., Richter, S., Huebner, P., Jabbour, T., Wegener, M. 3D fluorescence-based security
features by 3D laser lithography, Adv Mater Technol, 2017, 2, 1700212.
 Chapter 2 New free radical and cationic photoinitiators for two-photon 3D printing 105

[77] Lata, M., Li, Y. Z., Park, S., McLamb, M. J., Hofmann, T. Direct laser writing of birefringent
photonic crystals for the infrared spectral range, J Vac Sci Technol B, 2019, 37, 062905.
[78] Bertin, N., Spelman, T. A., Stephan, O., Gredy, L., Bouriau, M., Lauga, E., Marmottant,
P. Propulsion of bubble-based acoustic microswimmers, Phys Rev Appl, 2015, 4, 064012.
[79] Liao, C. Z., Anderson, W., Antaw, F., Trau, M. Two-photon nanolithography of tailored hollow
three-dimensional microdevices for biosystems, ACS Omega, 2019, 4, 1401–1409.
[80] Dong, Z. Q., Schumann, M. F., Hokkanen, M. J., Chang, B., Welle, A., Zhou, Q., Ras, R. H. A.,
Xu, Z. L., Wegener, M., Levkin, P. A. Superoleophobic slippery lubricant-infused surfaces:
Combining two extremes in the same surface, Adv Mater, 2018, 30, 1803890.
[81] Power, M., Thompson, A. J., Anastasova, S., Yang, G. Z. A monolithic force-sensitive 3D
microgripper fabricated on the tip of an optical fiber using 2-photon polymerization, Small,
2018, 14, 1703964.
Ignazio Roppolo, Annalisa Chiappone
Chapter 3
Functional dyes in light-induced 3D printing
3.1 Introduction
Humans began playing with colors since the prehistoric era, starting with red
color from ochre, when they created the first cave art painting. Since then, they
learned how to modify the aspect of the objects just by adding pigments or dyes to
the materials, both for aesthetic or functional purposes. Over the centuries, this
knowledge has been adapted to various applications including paintings, textiles
and ceramics [1].
The history of polymers started much later, in the nineteenth century, but since
its beginning, the dispersion of organic dyes or pigments in polymeric matrices has
acquired crucial importance [2].
In the polymeric industry, in many cases, colors are desired just for aesthetic
needs but, recently, the use of organic dyes has taken a step forward and is
being exploited to transfer peculiar functionalities to the inert polymeric matri-
ces [3–7].
Furthermore, in recent years, the use of pigments or dyes has found a further
application in the new, cutting-edge field of light-induced 3D printing [8]. At the
commercial level, Formlabs, one of the most known DLP/SL printer producers, is
now proposing a “color kit” containing five cartridges, with the different color pig-
ments aiming to allow every printer-user to obtain his own 3D object of the desired
color. But it is necessary to be aware that in light-induced 3D printing, the chromo-
phore molecules are more than colors, since they play an indispensable role in at-
taining the best printing resolution [9, 10].
It is, then, evident that exploiting the presence of these molecules could be an
intriguing possibility not only for the above-mentioned purposes (giving color or
improve printing resolution)but also because the choice of stimuli-responsive or
functional dye molecules can impart new properties to the polymeric 3D printable
materials without affecting the mechanical features of the printed objects, thanks
to the limited amount of dye that is usually required. Moreover, the possibility of
chemically decorating the structures of the chromophores allows their insertion in
the polymeric matrices either by dispersion or by covalently linking them to the
polymeric backbones.

Ignazio Roppolo, Annalisa Chiappone, Department of Applied Science and Technology DISAT,
Politecnico di Torino, Corso Duca degli Abruzzi, Torino, Italy

https://doi.org/10.1515/9783110570588-003
108 Ignazio Roppolo, Annalisa Chiappone

The use of functional dyes in 3D printing technologies has led to a relatively

unexplored research area in which materials properties and 3D structuration are
merged to offer new synergistic effects.
The scope of this chapter is to critically screen the recent advancements in the
use of dyes in light-induced 3D printing to create objects responsive to specific ex-
ternal stimuli such as light, pH, temperature or solvents.

3.2 3D printable formulations

Light-induced 3D printing techniques, also known as vat printing (VP) are those ad-
ditive manufacturing processes in which a three-dimensional object is built, layer
by layer, starting from a liquid photopolymer that is selectively cured by light-acti-
vated polymerization. The VP techniques include stereolithography (SL), Digital
Light Processing (DLP) and some more recent evolutions of these, such as Continu-
ous Liquid Interface Polymerization (CLIP) and Volumetric Additive Manufacturing
(VAM), furthermore, the most precise printing technology, that is, two photons po-
lymerization (TPP), must also be listed among the light-induced printing technolo-
gies [11, 12].
A common photocurable formulation, indicatively suitable for all the above-
mentioned 3D printing technologies, is composed of at least two components:
monomers and photoinitiator [13, 14].
Most of the commercial vat 3D printable materials are based on mixtures of
multifunctional acrylates monomers, but their exact formulation is usually confi-
dential. Besides the commercial materials, the formulations proposed in literature
are also based on bi- or multi-functional acrylates or methacrylates monomers that
are usually commercially available [15]. Some of the most common monomers are
reported in Figure 3.1.
Acrylates are usually chosen, thanks to their fast reactivity with partially lim-
ited surface conversion due to the oxygen inhibition that allows a good adhesion
between layers [16]. As drawback, these monomers suffer from volume shrinkage
during curing. Thus, many acrylate systems can show strong internal stresses that
could lead to poor resolution or even damage of the printed object. The choice of
methacrylate monomers can reduce the shrinkage problem; however, their curing
rate is slower than acrylates. Therefore, a mixture of the two could bring the best
compromise between adequate curing kinetics and low final shrinkage. Aromatic or
high molecular weight (meth) acrylates, characterized by lower volume shrinkage
but higher viscosity, can also be used [17]. In all the mentioned cases, the printing
parameters, that is, layer thickness, exposure time, light intensity and also separa-
tion velocity in the case of DLP, must be well-controlled and, furthermore, heating
of the formulation has also to be considered [18].
Figure 3.1: Chemical structure of commercially available polymers and monomer for application in 3D printing.
Chapter 3 Functional dyes in light-induced 3D printing
109
110 Ignazio Roppolo, Annalisa Chiappone

Thiol-ene/yne systems and epoxy bi- or multi-functional monomers can also be

used in light induced 3D printing. These classes of monomers are known for pre-
senting reduced shrinkage, fewer stresses and higher conversion in comparison to
acrylate monomers [19–21]. Nevertheless, epoxy monomers are characterized by
slow reaction kinetics, while in thiol-ene systems, the presence of C-S-C bonds im-
plies lower mechanical properties; this problem can be overcome by the addition of
allyl ethers to the thiol/methacrylate mixtures [22]. Furthermore, an increase in the
glass transition temperature of the polymers can be obtained by replacing alkene
with alkyne in mixture with thiols monomers, due to the increase of cross-linking
density of the network [23].
As a fundamental guideline for the choice of the monomers for a photocurable/
printable formulation, it is necessary to know that the reactive groups of the molecule
control the kinetics of the reaction, while the backbone influences the physicochemi-
cal characteristics of the final polymer (e.g., strength, hydrophilicity or brittleness),
so both the aspects should be taken into account [8].
As for the photoinitiator, it can be radical or cationic, according to the reactive
species that it generates, which involves different starting mechanisms for the poly-
merization [8]. Radical photopolymerization requires photosensitive initiators that
generate radicals when irradiated; a good variety of initiators absorbing in the UV
but also in the visible range are commercially available; thus, this kind of reaction
can be considered suitable for all the different VP techniques and is particularly
recommended for DLP printers that often present a light source emitting at 405 nm
[24]. Cationic photopolymerization, or eventually hybrid cationic/radical, is instead
more suitable for SLA, because a 355 nm UV laser is optimal to interact with those
photoinitiators [25]. More details on the recently developed photoinitiators (both
one-photon and two-photon) are presented in Chapters 1 and 2.
Beyond monomers and initiators, other ingredients can be found in 3D print-
able formulations:
(i) solvents/reactive diluents (short monofunctional monomers) that are used to
control the viscosity of the mixture; [26] (ii) fillers added to produce (nano) compo-
sites and to impart some specific properties [27].
The addition of fillers is the most common strategy used to overcome limitations
of polymeric materials and obtain specific properties such as electrical [28] or thermal
conductivity [29], luminescence or [30] stiffness. In this regard, 3D printing of differ-
ent composites has been reported in literature and recently reviewed [27, 31, 32].
At last, dyes or photoabsorbers may be added to the formulation [15]. Dyes are
commonly organic or organometallic molecules that can be dispersed in the liquid
formulation, or alternatively, they can be modified in order to be covalently linked
to the monomer/polymer chains [33].
The first reason for using dyes in a VP formulation is the improvement of the
printing resolution, as will be discussed in detail, in the following paragraphs. The
photoabsorber must compete with the photoinitiator in absorbing the radiation
 Chapter 3 Functional dyes in light-induced 3D printing 111

emitted by the light source, allowing to tune the kinetics of the reaction and to con-
fine the light diffusion in the vat [15]. Furthermore, most of the dyes impart a color
to the formulation and to the final object, so they are also often chosen for this final
purpose [34].
Nevertheless, the use of these compounds can go further, imparting specific func-
tionalities to the 3D printed structures allowing the direct shaping of light-emitting
devices, electroluminescent polymers, mechanochromic materials or light-switchable
gas permeable devices [30, 35–38].

3.3 Principle of photopolymerization and influence

of light absorbers
In most of the cases, photopolymerization occurs through a chain polymerization
mechanism, which is the continuous reaction of a propagating species (radical of
cation) with unreacted monomers to form a polymer chain [39]. This polymerization
mechanism could be described in three main steps:
– Initiations – the step in which reactive species are generated by light;
– Propagations – the step in which the unreacted monomers react with the active
species, leading to the formation of the polymeric chains/network; and
– Termination – the step in which the polymerization ends [40].

In this section, the principles of this polymerization mechanism are described with
particular attention to the influence of dye/photo absorbers. An alternative to
chain-mechanism is step-growth polymerization, which is mainly related to thiol-
ene/yne photopolymerization. Here, the kinetics of this polymerization mechanism
are not described as the details can be found elsewhere [41] and since the influence
of light absorbers is mainly in the initiation step that is common to the two photo-
polymerization mechanisms.
As mentioned, the first necessary step in photopolymerization consists of the
light-activated generation of reactive species. This occurs, thanks to the photoinitia-
tor that absorbs the radiation and generates the active species (eq. (3.1)):
hυ
PI ! R. Ri = Φi Iz ε½PI , (3:1)

where Ri is the rate of initiation, Φi is the initiation quantum yield, e ε is the molar
extinction coefficient at a given wavelength and Iz is the incident photonic flux.
This coefficient is related to the incident radiation (i.e., the radiation at the surface)
from the relation (eq. (3.2)):


IZ = Io 10 − A (3:2)
112 Ignazio Roppolo, Annalisa Chiappone

and A (the absorbance) is defined by the lambert Beer law (eq. (3.3)):

A = εzc (3:3)

where c is the concentration of the absorbing species – in the present case, the con-
centration of the photoinitiator. It is thus evident that the rate of the initiation (i.e.,
the efficiency at which the reaction starts) is directly dependent on the nature of
the photoinitiator (Φi) and on the light intensity. On the other hand, it is also clear
that given a certain absorbed light (Iz) using a certain light source (fixed Io), increas-
ing the photoinitiator concentration (c), the length of penetration (z) decreases. In
VP 3D printing, where a z-step is fixed (slicing), this aspect is of particular impor-
tance, since control over the penetration is necessary in order to allow adhesion of
the different layers and, conversely, not to induce overcuring, which means loss of
printing precision.
The propagation of the reaction occurs when an initiating species, R, reacts
with a monomer (M), generating a propagating reactive group that, by interaction
with other monomers, creates the growing polymeric chain (P.). This process is de-
fined by the following relation (eq. (3.4)):
M
R. + M ! RM. ! P. Rp = kp ½P. ½M (3:4)

where Rp is the rate of polymerization, and Kp is the constant of chain propagation.

Finally, termination occurs when two growing polymeric chains react, follow-
ing this mechanism (eq. (3.5)):

P. + P. ! Polymer Rt = kt ½P. 2 (3:5)

where Rt is the rate of termination, and Kt the kinetics constant of the reaction. By
combining these relations, the rate of polymerization can be expressed as follows
(eq. (3.6)):

kp
Rp = ½Ri 0.5 ½M (3:6)
kt0.5

This equation was demonstrated to be valid especially for monofunctional mono-

mers or multifunctional monomers in solutions. For conventional photopolymeri-
zation mechanisms, where termination usually occurs, for kinetics effect related
to decrease of species mobility in the polymeric network, a modification of this
kinetics equation is needed. However, a rigorous evaluation of the kinetics of the
photopolymerization is not the aim of this chapter, and one can refer to more de-
tail in literature [39]. Here, it is worthy to mention that the kinetics of polymeriza-
tion is proportional to the first power of the concentration of monomers and only
 Chapter 3 Functional dyes in light-induced 3D printing 113

to the square root of light intensity. So, the quantum yield of the polymerization,
(eq. (3.7)):
RP
ΦP = (3:7)
Iz

would decrease increasing light intensity. Furthermore, the rate of termination is

proportional to the square of the concentration of the propagating macromole-
cules (P.) which, in turn, is proportional to the amount of initiating species. It is
thus necessary to find a good compromise on the amount of photoinitiator, since
it is necessary to enable fast polymerization, but if in excess, could lead to high
termination and thus low conversion, with consequent effects on the materials
process [42].
In many applications of photopolymerization, it is merely required to have a
fast and effective conversion; in 3D printing, in addition to these aspects, it is man-
datory to have spatial control over the mechanism, in order to allow the production
of precise structures [43].
It is empirically possible to regulate the resolution of the product to obtain the
desired properties of the final object by adjusting the quantity and type of the pho-
toinitiator, the exposure time for each layer, as well as the energy of the light
source. Other important parameters that can affect the Cp are the light density, the
monomer reactivity, the temperature and the exposure time.
In this context, the addition of dyes and photoabsorbers plays a fundamental
role. In fact, considering a formulation, its absorbance (Af) can be defined by (eq.
(3.8)) as follows:
X
Af = z εi ci (3:8)

Hence, the total absorbance of a formulation (Af) is the result of the sum of the sin-
gle concentration and the single coefficients of molar extinction of the absorbing
groups present in a formulation, at a given wavelength. The dyes are chosen to
compete with the photoinitiator in light absorption, increasing the formulation’s
absorbance and decreasing the rate of initiation, with consequent effects on the
whole photopolymerization mechanism. In VP 3D printing, these results are of par-
ticular interest because a finer control over the mechanism allows to better define
the polymerization in XY plane, in order to avoid propagation out of the pixel of
irradiation.
Furthermore, the following relations must be taken in consideration (eq. (3.9)):
 
EMAX
Cd = Dp ln (3:9)
Ec
114 Ignazio Roppolo, Annalisa Chiappone

where Cd is the curing depth, Dp, the depth of the penetration of light, EMAX, the
energy dosage per units of area and Ec is the “critical” energy to activate the reac-
tion. Dp is empirically defined as (eq. (3.10)):
1
Dp = (3:10)
2.3ε½PI 

so inversely proportional to ε and to the concentration of photoinitiator. It is thus

obvious that by increasing the coefficient of molar extinction, the light depth pene-
tration decreases, decreasing, thus, the curing depth. The dyes, affecting this pa-
rameter, allow having a precise control over the Cd, which, in principle, should be
similar to the z-step of the 3D printing process [44].
In short, the dyes allow a precise control over the photopolymerization along Z
by controlling the depth of penetration of the light and help control the XYresolu-
tion, decreasing the rate of initiation and thus the whole polymerization reaction,
including its propagation and termination. Dyes are able to spatially confine the po-
lymerization process to the irradiated areas, according to the CAD file, avoiding
overcuring phenomena, both in width and depth. The amount of dyes loaded in
3DP matrices must be evaluated, considering the broadness of the absorption spec-
trum and the dye molar extinction coefficient, to minimize competitive photon ab-
sorption processes with other components like photoinitiators or photo cross-linkers.
An overall good resolution and fast polymerization are thus related to a well-eval-
uated balance between the dyes and the photoinitiator percentage in the matrix
[10, 43].

3.4 Conventional dyes in VP

Scanning the research-based literature on VP techniques, it is evident that dyes are
mostly used as additives for controlling the polymerization, as just explained, often
with an undesired final color, or, in some cases, just for aesthetical aspects, aiming
to control the color of the final object. However, their role is often underestimated
in researches, and it may happen that their presence is not mentioned at all.
A large variety of organic UV and visible light absorbers, belonging to different
chemical families (e.g., azobenzenes, benzotriazoles, etc.) have been used in differ-
ent works, covering a large part of the light absorption spectrum. Some of the dyes
most commonly found in literature are listed in Table 3.1.
As explained earlier, aiming at increasing the printing resolution, careful choice
of the correct dye and its correct amount must be done, considering the absorption
spectrum of the used photoinitiator, of the dye and the emission wavelength of the
printing machine. Most of the SL/DLP machines work with emissions ranging from
about 355 nm for some SL lasers up to 385/405 for common DLP equipment, and the
Table 3.1: List of most common dyes used in VP 3D printing.

Dye Formula λmax (nm) Concentration reported in literaturea

Avobenzone  . wt% in PEGDA for biomedical

Butyl applications []
methoxydibenzoylmethane % In PEGDA study for microfluidics
channels []

NPS   wt% in PEGDA BIO []

-nitrophenyl phenyl sulfide % In PEGDA study for microfluidics
channels []
% in PEGDA microchannels []

Tinuvin   –. wt % in a mixture of IBXA HDDA

-(′-Hydroxy-′,′-di-tert- and BEDA for D microstructures []
butylphenyl)-
-chlorobenzotriazole

Benetex OB  . wt% in a mixture of acrylic

,ʹ-(,-thiophenediyl)bis *Fluorescence monomers for clear transparent
(-tert-butylbenzoxazole) max.  nm materials []
.% In PEGDA study for microfluidics
channels []
Chapter 3 Functional dyes in light-induced 3D printing

(continued )
115
Table 3.1 (continued )
116

Dye Formula λmax (nm) Concentration reported in literaturea

Sudan I  ~ wt% in PEGDA for improved printing

Other names:  (nd) resolution []
Solvent Yellow  .–. wt% in a commercial UV curable
Solvent Orange R elastomer – TangoPlus for miniaturized
soft robotics []
~. wt% in PEGDMA for high
precision pH-Responsive Antimicrobial
hydrogel scaffolds []
–. wt % in acrylate/allyl/ thiol
mixture for a Frontal Conversion and
Uniformity study []
Ignazio Roppolo, Annalisa Chiappone

Methyl Red  . wt% in bio-based acrylate monomer

Other names: (below with high printing resolution []
Acid Red  pH .) . wt% in light processable starch
based hydrogels []
. wt% in phosphorescent bio-based
resin []

Reactive Orange   nm .–. wt. % in PEGDA/AETAC

Other names:  nm (nd) mixture for precise monolithic ion
Remazol absorbers []
Brilliant Orange R . wt% in PEGDA for precise conductive
structures []
, wt% in BEDA for the printing of micro
cantilever []
Brilliant Green  . wt% in PEGDA/CNC hydrogel []
Other names:  (nd)
Diamond Green,
Emerald Green,
Ethyl Green,

a
proportional to the monomer.
Chapter 3 Functional dyes in light-induced 3D printing
117
118 Ignazio Roppolo, Annalisa Chiappone

commonly used initiators absorb in those ranges; for this reason, we can find
the most of the dyes also absorbing in the UV range or at wavelengths below
500 nm [11].
While many papers just present the dye as an ingredient of the formulation
with the known function of photoabsorber, without commenting on its choice,
some others are devoted to the study of the most suitable dye and its correct con-
centration in the formulation. Sudan I is probably the most used photoabsorber,
and its use has been deeply investigated in order to limit the curing depth and ob-
tain better Z resolution [10, 51].
Many papers also report on the comparison of different dyes and their influence
on the printing resolution. As an example, Simon et al. [56] aiming to produce
monolithic ion exchange adsorbers, compared the light spectrum of three dyes: Re-
active Orange 16 (RO16), Tinuvin 326 and Sudan I. (Figure 3.2(b)). The authors ob-
served that all the considered dyes absorb light at 385 nm that corresponds to the
emission of the used printer, but Tinuvin 326 spectrum does not cover the whole
photoinitiator spectrum, resulting in inability to protect the formulation from early
polymerization in ambient light. Sudan I and RO16, however, show similar absor-
bance spectra, overlapping with the photoinitiator and thus ensuring full protection
in ambient light. The authors then evaluated the influence of the amount of RO 16
on the curing depth as a function of the exposure time. (Figure 3.2(c))
Other photoabsorbers, less common in VP, have also been studied by Yang et al.
[60] for the production of precise internal and external features by visible light DLP
printing. The influence of methylene blue, coccine and tartrazine on the polymeriza-
tion was investigated by analyzing the curing of convex cones and channels.
Observing the absorption spectra, the authors reported that at the printing
wavelength (405 nm), tartrazine was the most effective photoabsorber in slowing
down the photocuring reaction. Therefore, tartrazine addition had the most obvious
reducing effect on cone printability but improving effect on channel printability
(Figure 3.3(a)).
Following the same concept Gong et al. too evaluated the use of 20 UV absorb-
ers in terms of solubility in the monomer, absorbance, final material strength and
final resolution for the production of 18 µm × 20 µm channels [34, 46].
However, a few papers discuss the use of the dye mainly as functional for the
final aesthetic aspect of the object. Park et al. [34] developed a visible light-curable
resin that remains transparent at visible wavelength after curing. After the correct
choice of the initiator that allows avoiding the yellowish color given by the most of
visible-light initiators, a large variety of dyes, including food dyes and others in the
whole color spectrum are tested for the printing of complex structure, aiming at of-
fering a wide palette of slightly colored transparent resins.
Finally, some absorbers, for example, Benetex OB, are used as fluorescent whit-
eners that provide brighter looking colors. Such a molecule is, as example, pro-
posed in a patent [49] to yield a whiter appearance. In fact, it is able to absorb light
 Chapter 3 Functional dyes in light-induced 3D printing 119

(a) 2,500
1s 2s

2,000

1,500
CD (μm)

1,000

500

0
0.0 0.5 1.0 1.5 2.0
Omnirad 819 (wt.%)
(b) 1.0
Omnirad 819
RO16
Sudan 1
0.8 Tinuvin 326
Absorbance (–)

0.6

0.4

0.2

0.0
300 400 500 600 700
Wavelength (nm)
(c) 2,500
0.000 wt. % RO16
0.063 wt. % RO16
0.125 wt. % RO16
2,000 0.250 wt. % RO16

1,500
CD (μm)

1,000

500

0
1 10 100
Exposure time (s)

Figure 3.2: (a) Cure depth as function of Omnirad 819 (photoinitiator) concentration for exposure
times of 1 and 2 s (b) Absorbance spectrum of Omnirad 819 (50 ppm by weight in IPA) and the
analyzed dyes RO16, Sudan I and Tinuvin 326 (12.5 ppm in IPA/H2O). Printer’s output wavelength
was 385 nm (black dotted line). (c) Working curves at different concentrations of RO16 as
photoabsorber. Reprinted with permission from [56], Copyright Elsevier.
120 Ignazio Roppolo, Annalisa Chiappone

(a) (b)

Ф = 1.5 mm 2.000
4.00 DPPO
Height or depth (mm)

Convex cone Vertical channel

1.500 methylene blue
3.00

Absorbance
coccine
2.00 1.000 tartrazine

1.00 0.500

0.00 0.000
k lu e n e in e 300 400 500 600 700 800
Bla
n
eb cci raz
en Co Tar
t
t hyl Wavelength (nm)
Me

Figure 3.3: (a) Effect of different photoabsorbers (i.e., methylene blue, coccine and tartrazine) on
the printability of convex cone and vertical channel; (b) Wavelength scan results of the
photoinitiator (i.e., Diphenyl (2,4,6-trimethylbenzoyl) phosphine oxide, DPPO) and
photoabsorbers. Reprinted from [60].

in the near UV range (400 nm – 420 nm) acting as common dyes in VP, while fluo-
rescing light at wavelengths higher than its absorption, allowing the creation of
clear transparent materials using only near UV light sources (i.e., about 400 nm to
about 420 nm) instead of deep UV (<400 nm) light sources.
The evolution in the use of dyes in 3DP is the topic of interest of this review,
and it will be discussed in the following section, with particular focus on the syn-
thesis of stimuli-responsive and functional polymers.

3.5 Unconventional dyes in VP for functional

polymers
As largely introduced in the previous paragraphs, the use of dyes is almost neces-
sary for SLA and DLP 3D printing technologies. Beyond the conventional uses of
light absorbers, these molecules can be added in the printable formulations to con-
fer new functionalities to the 3D printable objects. Here, this novel use of dyes are
reported and innovative applications enabled by the use of dyes in VP are de-
scribed. Moreover, it is worthy to mention that the use of functional dyes in 3D
printing is not limited to light-activated technologies, and at the end of this para-
graph, a brief overview of their use in other 3D printing methods is given.
Methyl Red (MR) and Disperse Red 1 Methacrylate (DR1MA), two azobenzene
dyes, were used to light-trigger the mechanical properties of 3D printable structures.
 Chapter 3 Functional dyes in light-induced 3D printing 121

In this study, two polymeric matrices having different glass transition temperatures
(at room temperature one matrix was in the glass state while the other one was in
rubbery state) but similar chemical structures were used to incorporate the dyes and
analyze their effect [36]. The mechanical properties of these materials and, in particu-
lar, Young’s moduli, were triggered using an external light source (laser irradiation at
532 nm). Interestingly, it was observed that the two polymeric matrices showed oppo-
site behavior: while the glassy polymer showed photosoftening under laser irradia-
tion, the rubbery one showed a photohardening behavior. Furthermore, it was
demonstrated that this photosoftening/photohardening behavior can be obtained in
the same material, by testing the photoresponse at different temperatures (above and
beyond the glass transition temperature of the material respectively). This informa-
tion was used to fabricate micro cantilevers by 3D printing with local photo-induced
control of the oscillating behavior [36] and single frequency active filters [36].
The same molecules were also exploited to produce 3D printed devices with pho-
tocontrolled gas permeability [35]. Polymeric membranes containing those dyes were
3D printed (Figure 3.4(b)) and used to test the CO2 and O2 permeability under laser
beam irradiation at 532 nm and at different humidity conditions. It was demonstrated
that CO2 permeability increased with light irradiation. Furthermore, this change was
completely reversible and linear toward light intensity, allowing a controllable tuning
of permeability. On the other hand, O2 permeability was not affected by light irradia-
tion, remaining constant with and without irradiation. These data were used to 3D
print prototype of photocontrolled gas separator. In this device, CO2 connection was
performed on the azobenzene-based membrane side, and its permeability was con-
trolled by laser irradiation. The photocontrol of CO2 flux was successfully measured
by monitoring the change in the pH of an aqueous solution.

(a) (b)

CO2 pipe
connector

Photo switchable
membrane

Laser transparent
window

Figure 3.4: (a) 3D printed cantilever containing azo dyes. Reproduced from [36] with permission
from The Royal Society of Chemistry. (b) 3D printed prototype gas separator. Reprinted with
permission from [35], Copyright Elsevier.
122 Ignazio Roppolo, Annalisa Chiappone

It was also reported on the use of other stimuli-responsive compounds that can
react to the variations of physical forces, such as light and temperature. For instance,
anthracene was used in different polymeric matrices (Figure 3.5) [61]. In fact, anthra-
cene can give [4 + 4] cycloaddition generating under light with λ > 300 nm, while the
reaction can be reversed under irradiation with λ < 300 nm. This property was used
to 3D print material based on poly(D,L-lactide)-poly(tetramethylene oxide) glycol co-
polymers (AN-PDLLAPTMEG) with different percentages of PDLLA, which showed
shape recovery properties. Furthermore, those materials can be 3D printed in SLA or
DLP without the use of photoinitiators, ensuring increased biosafety and thus, possi-
ble applications in biomedical field. In that work, it was also demonstrated that co-
polymers containing anthracene exhibit shape memory responsivity using both light
and temperature as external stimuli. Finally, the anthracene changes its fluorescence
emission after irradiation at 365 nm, which can be exploited to store information or
as anti-counterfeiting.

Figure 3.5: Shape memory behavior of 3D printed specimens containing anthracene. Reprinted with
permission from [61], Copyright Elsevier.

Another option given by functional dyes consists of the preparation of 3D printable

fluorescent resins that can emit different regions of visible spectra, producing either
primary colors or white-emitting devices [38]. In this case, three different functional
additives were employed, dispersed in acrylate resins: 2,2ʹ-(2,5-Thienediyl)bis[5-(2-
methyl-2-propanyl)-1,3-benzoxazole] (BBOT, blue emitter), Solvent Yellow 98 ( green
emitter) and Rhodamine B (red emitter) (Figure 3.6(a)). The resulting formulations
were 3D printed, showing excellent resolution and controlled emission. Furthermore,
mixing the three primary colors, white-emitting formulations were obtained.
Other photoluminescent dyes were used to fabricate high-tech devices like
waveguides. The use of methacrylate benzoxadiazole as smart dye in acrylic formu-
lations (Figure 3.6(b)) was reported. In this work, both the printability of the objects
and the emitting properties were investigated, evidencing a necessary trade-off, in
order to obtain precise structures and efficient light emission. Furthermore, those
devices showed application in polarity sensors, since light emission changed, inter-
acting with different solvents [30].
Chemosensing applications employing coordination polymers were explored,
due to their flexible chemistry, dynamic structures and possibility to create stimuli-
 Chapter 3 Functional dyes in light-induced 3D printing 123

Figure 3.6: (a) Emissive resins and white emission sample generated using different light emitting
dyes. Reprinted with permission from [38], Copyright Jon Wiley and Sons. (b) Illuminated
waveguides containing benzoxadiazole. Reprinted with permission from [30], Copyright 2018
American Chemical Society.

responsive devices. For instance, 4–4ʹ-bipyridine was used to coordinate copper (II)
1D to develop coordination polymer (Figure 3.7(a)), then dispersed in photocurable
matrices [62]. The polymer showed a color shift from blue to violet, characterized by
coordination and solvation of water molecules. This dehydration process was dem-
onstrated to be reversible, making this material suitable for use as moisture sen-
sors, as well as in organic solvents.
Copper-mediated azide-alkyne cycloaddition was used to functionalize polyest-
ers with modified coumarin in order to control the emission of the matrices [63]. In
that case, 3D printed objects produced with continuous DLP (cDLP) were post-
treated to create emitting devices (Figure 3.7(b)).
Similar compounds were employed in regenerative medicine, thanks to their
biocompatibility and their safe degradation by-products. Discs of poly (propylene
fumarate) (PPF) containing propargyl alcohol moieties, 3D printed with cDLP, were
functionalized by means of azide-alkyne click mechanism (Figure 3.7(c)) [64]. The
success of the reaction is shown in the final color of the objects. Similarly, PPF
discs were functionalized with azide peptides to prepare biocompatible scaffolds
for biomedical applications.
Another alternative use of dye is in the production of mechanophore polymeric
materials; that is, materials that can change their color in response to mechanical
stress. Mechanochromic dyes are a class of chromophores known to change color
when subjected to mechanical stress [65]. For instance, such materials were pro-
duced using HydroxyEthyl Acrylate and oxanorbornadiene [66]. DLP equipment
emitting in the visible range was used to prepare the samples in order to avoid
124 Ignazio Roppolo, Annalisa Chiappone

Figure 3.7: (a) Polymer containing bipyridine compound: color change due to hydratation/
dehydratation. Reprinted with permission from [62], Copyright Jon Wiley and Sons. (b) Printed
fluorescent polyester structures. Reprinted with permission from [63] Copyright 2018 American
Chemical Society. (c) Microscopy image of PPF disc functionalized. Reprinted with permission from
[64], Copyright 2018 American Chemical Society.

degradation of dye. The mechanical stress (compression) of the samples that fol-
lowed for one minute induced the chemical modification of the structure into the
molecular constituents of oxanorbornadiene.
All these examples prove the possibility of obtaining functional materials merg-
ing with SLA/DLP technique and different dyes. The use of dyes is rarely reported
in the last light-activated technology, two-photon polymerization (TPP), since the
multiple-photon polymerization mechanism with an ultra-focalized irradiation al-
ready ensures resolutions down to the nanometric scale, making the use of the dye
redundant according to common perception.
Nevertheless, some works presenting the use of smart dyes in TPP have been
proposed.
Diacrylate azo dyes have been prepared, and their trans/cis photoisomerization
when cured in the presence of MMA and their applicability in TPP have been evalu-
ated [67]. In this case, alkyl and bulky groups were introduced on the dyes’ struc-
ture to improve the solubility and the dispersion in the monomer mixture, avoiding
the formation of gel with consequent dyes aggregation while printing photonic crys-
tals (Figure 3.8(a)).
In a work by Descrovi et al., a similar azobenzene dye bearing one methacylic
group was embedded in a rigid matrix made of BEDA (2EO) to print nanometric
membranes with a rapid and reversible deformation. As reported in Figure 3.8(b)
[68], a square membrane of 120 µm was produced under 532 nm laser irradiation;
 Chapter 3 Functional dyes in light-induced 3D printing 125

Figure 3.8: (a) SEM image of photonic crystal. Reprinted with permission from [67], Copyright Jon
Wiley and Sons. (b) SEM image micro printed membrane. Reprinted from [68] with permission from
The Royal Society of Chemistry. (c) Fabricated giraffe. Reprinted with permission from [69],
Copyright 2010 American Chemical Society.

the membrane shows a volume expansion of 28% and a decrease in the refractive
index of about 0.16. The process was demonstrated to be reversible by switching
the laser on and off several times and observing the cyclic deformation and recov-
ery of the object shape. Nevertheless, photobleaching of the dye, probably due to
the energetic laser irradiation, was observed.
Coumarins have also been applied in TPP. Given their photosensitivity, they
have been added to printing formulations, with the aim of reducing the amount of
photoinitiator limiting the unreacted sub-products residue left at the end of the po-
lymerization [69]. For this work, different substituent groups were added to couma-
rin molecules to expand the conjugation, covering the visible spectra, to enhance
the photosensitizer effect. This way, it was possible to reduce the photoinitiator
concentration from 1–2% to 0.4%, achieving a good printing resolution as shown in
Figure 3.8(c). Light-emitting 3D microstructures and nanostructures were produced
embedding coumarin and other commercial dyes such as fluorescein in the printing
formulation, without reducing the printing resolution and enabling the internal
structure verification by optical microscopy [70]. Coumarin-based ketones were in-
stead used as initiators in TPP [71] and, similarly, coumarins bearing oxime-esters
groups were used to start the polymerization process with low-intensity laser upon
irradiation in the 400–460 nm spectral window [72].
The possibility of creating new materials that are responsive to external stimuli
could lead to improvement in device performances across biomedical, functional
materials, basic science and industrial applications fields. Further inspiration could
come from other 3D printing technologies in which different dyes were used.
In Fused Filament Fabrication (FFF) 3D printing, a few functional dyes were used
to study possible thermal degradation during the extrusion process. For instance,
126 Ignazio Roppolo, Annalisa Chiappone

mechanochromic spiropyranes have been used in sample material produced by

FFF to evidence a color change (from colorless to purple) under mechanical stress
[73]. In this case, the polymers were extruded at 110 °C, without evidencing ther-
mal degradation. The reversible color changes were demonstrated to be responsive
to external mechanical stress or to UV irradiation, suggesting different applications
as sensors (Figures 3.9(a, b)).

Figure 3.9: Specimen with spiropyranes as additive, before and after irradiation at 365 nm as well
as under and after load application. Adapted with permission from [73], Copyright 2015 American
Chemical Society.

Thermochromic polymers were obtained, using alkoxyphenyl N-substituted naph-

thalene diimides (NDI) in PLA [74, 75]. The control of thermochromism can be
achieved by modulating the alkoxyphenyl chain length, making these materials po-
tentially suitable as thermal sensors (Figures 3.10(b, c)).
Direct ink Writing (DIW) is another 3D printing that can be an inspiration in
this field, since it is a very good option for the development of functional materials
using dyes, as it operates at room temperature, employing pastes or liquids. Using
this technology, photoluminescent hydrogels were 3D printed and used to evaluate
the O2 concentration available for cells [76]. In that case, an O2-sensitive lumines-
cent platinum (II) meso(2,3,4,5,6-pentafluoro)phenyl porphyrin dye and a coumarin
derivative as a fluorescence standard were used. The platinum complex gave red
emission upon excitation with blue wavelength, and it could change its emission as
a function of O2 concentration. This probe was successfully used to map the oxygen
concentration in printed objects (Figure 3.11(a)).
Spiropyrans were also used in DIW in combination dispersed in silicone inks
[77]. The reversible color switch between spiropyran and the merocyanine was either
under compression or elongation. (Figure 3.11(b)). Coumarin was used to reversibly
tune the mechanical properties of polymers under UV irradiation [78]. Coumarin
groups react via a [2 + 2] cycloaddition to form under UV light. Thanks to this reac-
tion, a 3D printable and biodegradable polyesters with tunable mechanical properties
 Chapter 3 Functional dyes in light-induced 3D printing 127

Figure 3.10: (a) Thermochromic behavior of NDIs at 100 and −173 °C. (b) Reversible thermochromic
behavior of composite between PLA and NDI. Adapted from [74] with permission from The Royal
Society of Chemistry.

(in this case cross-linking) can be obtained. In fact, the obtained viscoelastic ink
changes its properties under irradiation at 350 nm, generating an elastomeric matrix
(Figure 3.11(c)). The same approach was used to fabricate reversible cross-linked hy-
drogels, exploiting the reversible [2 + 2] cycloaddition of coumarin [79]. Irradiating at
254 nm of the prepared hydrogels led to de-cross-linking and reversible degradation
into water-soluble copolymer. Finally, azobenzene dyes were also used to achieve re-
versible deformation in DIW printed polymers (Figure 3.11(d)) [80]. Polymethylhydro-
siloxane (PHMS) with molecular weight of 2,100–2,400 g/mol were functionalized
with different azobenzene moieties by means of hydrosilylation reactions. Then, DIW
3D printing of the inks was performed on a polyimide film to guarantee flexibility
and chemical resistance. Upon irradiation at 442 nm, these materials showed defor-
mation that could be totally recovered, once the light was turned off.

3.6 Conclusions and perspectives

As reported, in light-activated 3DP, dyes have two conventional uses: first, for aes-
thetical reasons (i.e., to give the desired color/transparency), and second, as ingre-
dients employed to enhance light control and, thus, the resolution of the printed
structures. However, recent research activities witnessed the possibility of adding a
further use for the dyes; that is, as ingredient for producing functional materials.
128 Ignazio Roppolo, Annalisa Chiappone

Figure 3.11: (a) Spatiotemporal dynamics of O2 concentration depicted by hydrogel containing

porphyrins and a layer of microalgae. Reprinted with permission from [76], Copyright Jon Wiley and
Sons. (b) 3D printed samples based on silicone/spiropyrane inks. Images taken before and after
application of force or compression, showing a color change. Reprinted from [77] with permission
from The Royal Society of Chemistry. (c) 3D printed bio renewable polyester containing coumarin.
Reprinted with permission from [78], Copyright 2016 American Chemical Society. (d) Images of
polymer matrix containing azobenzene dyes with UV LED off and on. Reprinted with permission
from [80], Copyright 2018 American Chemical Society.

In this chapter, we reported the basic principles regarding the photopolymeriza-

tion and the influence of light absorbers on this mechanism, describing how these
were used up to now for achieving good resolution. It is important to highlight, that
in a 3D printable formulation, the dyes should be carefully selected, taking into ac-
count both the emission range of the light source and the absorption spectra of the
photoinitiator. In fact, if competitive light absorption occurs between the two ingre-
dients, it will be possible to control the photopolymerization mechanism better, by
controlling the light penetration on the z-axis and avoiding overcuring of the resins.
Furthermore, dyes can confer specific characteristics such as triggering of the
mechanical properties, modification of the optical properties, control over bulk
(e.g., permeability) or surface (e.g., wettability) properties.
 Chapter 3 Functional dyes in light-induced 3D printing 129

In a perspective view, different 3D printed objects can be produced, with a syner-

gistic effect of the material’s properties and the shape of the objects. In this context,
waveguides, sensors for gases and liquids and biomedical devices can be produced.
Future applications can be based on the inclusion of other responsive dyes that have
not been explored, at the moment. Among the possible applications, pH sensors,
thermometers, devices with tunable hydrophilicity/hydrophobicity, devices for con-
trolled drug delivery and actuators can be mentioned. It is worth highlighting that for
biomedical applications, biocompatibility of light absorbers and of possible degrada-
tion byproducts as well as their migration must be considered.
The wide variety of possible functionalities provided by the addition of small
quantities of dyes in common polymeric matrices will prompt both academic and
industrial researchers to progress even further in this field.

References
[1] Evans, G. The story of colour: An exploration of the hidden messages of the spectrum,
Michael O’Mara Books Ltd, UK, 2017.
[2] Ebewele, R. O. Polymer science and technology, CRC Taylor and Francis Group: USA, 2000.
[3] Pucci, A., Ruggeri, G. Mechanochromic polymer blends, J Mater Chem, 2011, 21, 8282–8291.
[4] Barber, R. W., McFadden, M. E., Hu, X., Robb, M. J. Mechanochemically gated photoswitching:
Expanding the scope of polymer mechanochromism, Synlett, 2019, 30, 1725–1732.
[5] Breul, A. M., Hager, M. D., Schubert, U. S. Fluorescent monomers as building blocks for dye
labeled polymers: Synthesis and application in energy conversion, biolabeling and sensors,
Chem Soc Rev, 2013, 42, 5366–5407.
[6] Li, D., Wang, J., Ma, X. White-light-emitting materials constructed from supramolecular
approaches, Adv Opt Mater, 2018, 6, 1800273.
[7] Pietsch, C., Schubert, U. S., Hoogenboom, R. Aqueous polymeric sensors based on
temperature-induced polymer phase transitions and solvatochromic dyes, Chem Commun,
2011(47), 8750–8765.
[8] Zhang, J., Xiao, P. 3D printing of photopolymers, Polym Chem, 2018, 9, 1530–1540.
[9] Gao, Y., Xu, L., Zhao, Y., You, Z., Guan, Q. 3D printing preview for stereo-lithography based
on photopolymerization kinetic models, Bioact Mater, 2020, 5, 798–807.
[10] Vitale, A., Cabral, J. T. Frontal conversion and uniformity in 3D printing by
photopolymerisation, Materials, 2016, 9, 760–765.
[11] Quan, H., Zhang, T., Xu, H., Luo, S., Nie, J., Zhu, X. Photo-curing 3D printing technique and its
challenges, Bioact Mater, 2020, 5, 110–115.
[12] Ngo, T. D., Kashani, A., Imbalzano, G., Nguyen, K. T. Q., Hui, D. Additive manufacturing (3D
printing): A review of materials, methods, applications and challenges, Compos Part B: Eng,
2018, 143, 172–196.
[13] Layani, M., Wang, X., Magdassi, S. Novel Materials for 3D Printing by Photopolymerization,
Adv Mater, 2018, 30, 1706344.
[14] Crivello, J. V., Reichmanis, E. Photopolymer materials and processes for advanced
technologies, Chem Mater, 2014, 26, 533–548.
[15] Ligon, S. C., Liska, R., Stampfl, J., Gurr, M., Mülhaupt, R. Polymers for 3D printing and
customized additive manufacturing, Chem Rev, 2017, 117, 10212–10290.
130 Ignazio Roppolo, Annalisa Chiappone

[16] Bagheri, A., Jin, J. Photopolymerization in 3D Printing, ACS Appl Polym Mater, 2019,
1, 593–611.
[17] Kim, L. U., Kim, J. W., Kim, C. K. Effects of molecular structure of the resins on the volumetric
shrinkage and the mechanical strength of dental restorative composites,
Biomacromolecules, 2006, 7, 2680–2687.
[18] Stansbury, J. W., Idacavage, M. J. 3D printing with polymers: Challenges among expanding
options and opportunities, Dent Mater, 2016, 32, 54–64.
[19] Lu, H., Carioscia, J. A., Stansbury, J. W., Bowman, C. N. Investigations of step-growth thiol-
ene polymerizations for novel dental restoratives, Dent Mater, 2005, 21, 1129–1136.
[20] Chen, L., Wu, Q., Wei, G., Liu, R., Li, Z. Highly stable thiol–ene systems: From their structure–
property relationship to DLP 3D printing, J Mater Chem C, 2018, 6, 11561–11568.
[21] Dillman, B. F. The kinetics and physical properties of epoxides, acrylates, and hybrid epoxy-
acrylate photopolymerization systems, University of Iowa: USA, 2013.
[22] Sycks, D. G., Wu, T., Park, H. S., Gall, K. Tough, stable spiroacetal thiol-ene resin for 3D
printing, J Appl Polym Sci, 2018, 135, 46259.
[23] Oesterreicher, A., Wiener, J., Roth, M., Moser, A., Gmeiner, R., Edler, M., Pinter, G., Griesser,
T. Tough and degradable photopolymers derived from alkyne monomers for 3D printing of
biomedical materials, Polym Chem, 2016, 7, 5169–5180.
[24] Fouassier, J. P., Allonas, X., Burget, D. Photopolymerization reactions under visible lights:
Principle, mechanisms and examples of applications, Prog Org Coat, 2003, 47, 16–36.
[25] Sangermano, S. Advances in cationic photopolymerization, Pure Appl Chem, 2012, 84,
2089–2101.
[26] Andrzejewska, E., Andrzejewski, M. Polymerization kinetics of photocurable acrylic resins,
J Polym Sci A Polym Chem, 1998, 36, 665–673.
[27] Wang, X., Jiang, M., Zhou, Z., Gou, J., Hui, D. 3D printing of polymer matrix composites:
A review and prospective, Compos Part B: Eng, 2017, 110, 442–458.
[28] Gonzalez, G., Chiappone, A., Roppolo, I., Fantino, E., Bertana, V., Perrucci, F., Scaltrito,
L., Pirri, F., Sangermano, M. Development of 3D printable formulations containing CNT with
enhanced electrical properties, Polym, 2017, 109, 246–253.
[29] Hu, G., Cao, Z., Hopkins, M., Lyons, J. G., Brennan-Fournet, M., Devine, D. M. Nanofillers can
be used to enhance the thermal conductivity of commercially available SLA resins, Procedia
Manuf, 2019, 38, 1236–1243.
[30] Frascella, F., González, G., Bosch, P., Angelini, A., Chiappone, A., Sangermano, M., Pirri,
C. F., Roppolo, I. Three-dimensional printed photoluminescent polymeric waveguides, ACS
Appl Mater Interfaces, 2018, 10, 39319–39326.
[31] Tan, H. W., An, J., Chua, C. K., Tran, T. Metallic nanoparticle inks for 3D printing of
electronics, Adv Electron Mater, 2019, 5, 1800831.
[32] Taormina, G., Sciancalepore, C., Messori, M., Bondioli, F. 3D printing processes for
photocurable polymeric materials: Technologies, materials, and future trends, J Appl
Biomater Funct Mater, 2018, 16, 151–160.
[33] Gürses, A., Açıkyıldız, M., Güneş, K., Gürses, M. S. Dyes and pigments: Their structure and
properties. dyes and pigments, Eds, Springer International Publishing: Cham, 2016, 13–29.
[34] Park, H. K., Shin, M., Kim, B., Park, J. W., Lee, H. A visible light-curable yet visible
wavelength-transparent resin for stereolithography 3D printing, NPG Asia Mater, 2018, 10,
82–89.
[35] Gillono, M., Roppolo, I., Frascella, F., Scaltrito, L., Pirri, C. F., Chiappone, A. CO2 permeability
control in 3D printed light responsive structures, Appl Mater Today, 2019, 18, 100470.
[36] Roppolo, I., Chiappone, A., Angelini, A., Stassi, S., Frascella, F., Pirri, C. F., Ricciardi, C.,
Descrovi, E. 3D printable light-responsive polymers, Materials Horizons, 2017, 4, 396–401.
 Chapter 3 Functional dyes in light-induced 3D printing 131

[37] Gliozzi, A. S., Miniaci, M., Chiappone, A., Bergamini, A., Morin, B., Descrovi, E. Tunable
photo-responsive elastic metamaterials, Nat Commun, 2020, 11, 2576.
[38] Wang, F., Chong, Y., Wang, F., He, C. Photopolymer resins for luminescent three-dimensional
printing, J Appl Polym Sci, 2017, 134, 44988.
[39] Purbrick, M. D. Photoinitiation, photopolymerization and photocuring, J.-P. Fouassier. Hanser
Publishers: Munich, 1995.
[40] Yagci, Y., Jockusch, S., Turro, N. J. Photoinitiated polymerization: Advances, challenges, and
opportunities, Macromolecules, 2010, 43, 6245–6260.
[41] Hoyle, C. E., Bowman, C. N. Thiol–Ene Click Chemistry, Angew Chem Int Ed, 2010, 49,
1540–1573.
[42] Fouassier, J. P., Rabek, J. F. Radiation curing in polymer science and technology:
Fundamentals and methods, Springer Netherlands: NL, 1993.
[43] Ahn, D., Stevens, L. M., Zhou, K., Page, Z. A. Rapid High-Resolution Visible Light 3D Printing,
ACS Cent Sci, 2020, 6, 1555–1563.
[44] Lin, J. T., Liu, H. W., Chen, K. T., Cheng, D. C. Modeling the kinetics, curing depth, and efficacy
of radical-mediated photopolymerization: The role of oxygen inhibition, viscosity, and
dynamic light intensity, Front Chem, 2019, 7, 760.
[45] Warr, C., Valdoz, J. C., Bickham, B. P., Knight, C. J., Franks, N. A., Chartrand, N., Van Ry,
P. M., Christensen, K. A., Nordin, G. P., Cook, A. D. Biocompatible PEGDA resin for 3D printing,
ACS Appl Bio Mater, 2020, 3, 2239–2244.
[46] Gong, H., Bickham, B. P., Woolley, A. T., Nordin, G. P. Custom 3D printer and resin for
18 μm × 20 μm microfluidic flow channels, Lab Chip, 2017, 17, 2899–2909.
[47] Gong, H., Woolley, A. T., Nordin, G. P. 3D printed high density, reversible, chip-to-chip
microfluidic interconnects, Lab Chip, 2018, 18, 639–647.
[48] Choi, J. W., Wicker, R. B., Cho, S. H., Ha, C. S., Lee, S. H. Cure depth control for complex 3D
microstructure fabrication in dynamic mask projection microstereolithography, Rapid
Prototyping J, 2009, 15, 59–70.
[49] Liu, H., He, C. Additive use for enhancing the performance of photopolymer resin for 3d
printing. US Patent US 2017/0022311 A1; 2017.
[50] Lee, M. P., Cooper, G. J. T., Hinkley, T., Gibson, G. M., Padgett, M. J., Cronin, L. Development
of a 3D printer using scanning projection stereolithography, Sci Rep, 2015, 5, 9875.
[51] Zhang, Y. F., Ng, C. J. X., Chen, Z., Zhang, W., Panjwani, S., Kowsari, K., Yang, H. Y., Ge,
Q. Miniature pneumatic actuators for soft robots by high-resolution multimaterial 3D printing,
Adv Mater Technol, 2019, 4, 1900427.
[52] Garcia, C., Gallardo, A., López, D., Elvira, C., Azzahti, A., Lopez-Martinez, E.,
Cortajarena, A. L., González-Henríquez, C. M., Sarabia-Vallejos, M. A., Rodríguez-Hernández,
J. Smart pH-responsive antimicrobial hydrogel scaffolds prepared by additive manufacturing,
ACS Appl Bio Mater, 2018, 1, 1337–1347.
[53] Cosola, A., Conti, R., Grützmacher, H., Sangermano, M., Roppolo, I., Pirri, C. F., Chiappone,
A. Multiacrylated cyclodextrin: A bio-derived photocurable macromer for VAT 3D printing,
Macromol Mater Eng, 2020, 305, 2000350.
[54] Noè, C., Tonda-Turo, C., Chiappone, A., Sangermano, M., Hakkarainen, M. Light processable
starch hydrogels, Polym, 2020, 12, 1359.
[55] Maturi, M., Pulignani, C., Locatelli, E., Vetri Buratti, V., Tortorella, S., Sambri, L., Comes
Franchini, M. Phosphorescent bio-based resin for digital light processing (DLP) 3D-printing,
Green Chem, 2020, 22, 6212–6224.
[56] Simon, U., Dimartino, S. Direct 3D printing of monolithic ion exchange adsorbers,
J Chromatogr A, 2019, 1587, 119–128.
132 Ignazio Roppolo, Annalisa Chiappone

[57] Fantino, E., Chiappone, A., Roppolo, I., Manfredi, D., Bongiovanni, R., Pirri, C. F., Calignano,
F. 3D printing of conductive complex structures with in situ generation of silver
nanoparticles, Adv Mater, 2016, 28, 3712–3717.
[58] Stassi, S., Fantino, E., Calmo, R., Chiappone, A., Gillono, M., Scaiola, D., Pirri, C. F., Ricciardi,
C., Chiadò, A., Roppolo, I. Polymeric 3D printed functional microcantilevers for biosensing
applications, ACS Appl Mater Interfaces, 2017, 9, 19193–19201.
[59] Wang, J., Chiappone, A., Roppolo, I., Shao, F., Fantino, E., Lorusso, M., Rentsch, D., Dietliker,
K., Pirri, C. F., Grützmacher, H. All-in-one cellulose nanocrystals for 3D printing of
nanocomposite hydrogels, Angew Chem Int Ed, 2018, 57, 2353–2356.
[60] Yang, Y., Zhou, Y., Lin, X., Yang, Q., Yang, G. Printability of external and internal structures
based on digital light processing 3D printing technique, Pharm, 2020, 12, 207.
[61] Xie, H., Yang, K. K., Wang, Y. Z. Photo-cross-linking of anthracene as a versatile strategy to
design shape memory polymers, Mater Today: Proc, 2019, 16, 1524–1530.
[62] Maldonado, N., Vegas, V. G., Halevi, O., Martínez, J. I., Lee, P. S., Magdassi, S., Wharmby,
M. T., Platero-Prats, A. E., Moreno, C., Zamora, F., Amo-Ochoa, P. 3D printing of a thermo- and
solvatochromic composite material based on a Cu(II)–thymine coordination polymer with
moisture sensing capabilities, Adv Funct Mater, 2019, 29, 1808424.
[63] Petersen, S. R., Wilson, J. A., Becker, M. L. Versatile ring-opening copolymerization and
postprinting functionalization of lactone and poly(propylene fumarate) block
copolymers: Resorbable building blocks for additive manufacturing, Macromolecules,
2018, 51, 6202–6208.
[64] Wilson, J. A., Luong, D., Kleinfehn, A. P., Sallam, S., Wesdemiotis, C., Becker, M. L.
Magnesium catalyzed polymerization of end functionalized Poly(propylene maleate) and
Poly(propylene fumarate) for 3D printing of bioactive scaffolds, J Am Chem Soc, 2018, 140,
277–284.
[65] Ciardelli, F., Ruggeri, G., Pucci, A. Dye-containing polymers: Methods for preparation of
mechanochromic materials, Chem Soc Rev, 2013, 42, 857–870.
[66] Cao, B., Boechler, N., Boydston, A. J. Additive manufacturing with a flex activated
mechanophore for nondestructive assessment of mechanochemical reactivity in complex
object geometries, Polym, 2018, 152, 4–8.
[67] Wang, H., Jin, F., Chen, S., Dong, X. Z., Zhang, Y. L., Chen, W. Q., Zhao, Z. S., Duan, X. M.
Preparation, photoisomerization, and microfabrication with two-photon polymerization of
crosslinked azo-polymers, J Appl Polym Sci, 2013, 130, 2947–2956.
[68] Descrovi, E., Pirani, F. P., Rajamanickam, V., Licheri, S., Liberale, C. Photo-responsive
suspended micro-membranes, J Mater Chem C, 2018, 6, 10428–10434.
[69] Xue, J., Zhao, Y., Wu, F., Fang, D. C. Effect of bridging position on the two-photon
polymerization initiating efficiencies of novel coumarin/benzylidene cyclopentanone dyes,
J Phys Chem A, 2010, 114, 5171–5179.
[70] Žukauskas, A., Malinauskas, M., Kontenis, L., Purlys, V., Paipulas, D., Vengris, M., Gadonas,
R. Organic dye doped microstructures for optically active functional devices fabricated via
two-photon polymerization technique, Lith J Phys, 2010, 50, 676–683.
[71] Nazir, R., Danilevicius, P., Ciuciu, A. I., Chatzinikolaidou, M., Gray, D., Flamigni, L., Farsari,
M., Gryko, D. T. π-Expanded ketocoumarins as efficient, biocompatible initiators for
two-photon-induced polymerization, Chem Mater, 2014, 26, 3175–3184.
[72] Qiu, W., Hu, P., Zhu, J., Liu, R., Li, Z., Hu, Z., Chen, Q., Dietliker, K., Liska, R. Cleavable
unimolecular photoinitiators based on oxime-ester chemistry for two-photon
three-dimensional printing, ChemPhotoChem, 2019, 3, 1090–1094.
[73] Peterson, G. I., Larsen, M. B., Ganter, M. A., Storti, D. W., Boydston, A. J. 3D-printed
mechanochromic materials, ACS Appl Mater Interfaces, 2015, 7, 577–583.
 Chapter 3 Functional dyes in light-induced 3D printing 133

[74] Dharmarwardana, M., Arimilli, B. S., Luzuriaga, M. A., Kwon, S., Lee, H., Appuhamillage,
G. A., McCandless, G. T., Smaldone, R. A., Gassensmith, J. J. The thermo-responsive behavior
in molecular crystals of naphthalene diimides and their 3D printed thermochromic
composites, CrystEngComm, 2018, 20, 6054–6060.
[75] Dharmarwardana, M., Welch, R. P., Kwon, S., Nguyen, V. K., McCandless, G. T., Omary, M. A.,
Gassensmith, J. J. Thermo-mechanically responsive crystalline organic cantilever, Chem
Commun, 2017, 53, 9890–9893.
[76] Trampe, E., Koren, K., Akkineni, A. R., Senwitz, C., Krujatz, F., Lode, A., Gelinsky, M., Kühl,
M. Functionalized bioink with optical sensor nanoparticles for O2 imaging in 3D-bioprinted
constructs, Adv Funct Mater, 2018, 28, 1804411.
[77] Rohde, R. C., Basu, A., Okello, L. B., Barbee, M. H., Zhang, Y., Velev, O. D., Nelson, A., Craig,
S. L. Mechanochromic composite elastomers for additive manufacturing and low strain
mechanophore activation, Polym Chem, 2019, 10, 5985–5991.
[78] Govindarajan, S. R., Xu, Y., Swanson, J. P., Jain, T., Lu, Y., Choi, J. W., Joy, A. A solvent and
initiator free, low-modulus, degradable polyester platform with modular functionality for
ambient-temperature 3D printing, Macromolecules, 2016, 49, 2429–2437.
[79] Kabb, C. P., O’Bryan, C. S., Deng, C. C., Angelini, T. E., Sumerlin, B. S. Photoreversible
covalent hydrogels for soft-matter additive manufacturing, ACS Appl Mater Interfaces, 2018,
10, 16793–16801.
[80] Hagaman, D. E., Leist, S., Zhou, J., Ji, H. F. Photoactivated polymeric bilayer actuators
fabricated via 3D printing, ACS Appl Mater Interfaces, 2018, 10, 27308–27315.
Lubna Shahzadi, Feng Li, Fernando Maya Alejandro,
Michael C. Breadmore, Stuart C. Thickett
Chapter 4
Resin design in stereolithography 3D
printing for microfluidic applications

4.1 Introduction
Additive manufacturing (AM), also known broadly as 3D printing, has enticed the
research community and industries alike in the past few decades. The advancement
in AM techniques has influenced the material quality and product design in addi-
tion to how these products are being perceived and utilized by the consumers [1–3].
The 3D printing techniques have greatly simplified prototype manufacturing and
the translation of conceptual designs. Moreover, AM techniques have made it possi-
ble to complete complex designs in a shorter time with the desired lot size and ac-
cording to the consumer demand. Customized designs and products can also be
manufactured without making drastic changes to the entire production set-up [4].
According to the ASTM standard, AM techniques can be divided into seven
groups: stereolithography (SLA), fused deposition modeling (FDM), selective laser
sintering (SLS), material jetting, binder jetting, direct energy deposition and lami-
nated object manufacturing (LOM). These techniques are already being used for the
industrial preparation of several products covering various fields; for example, con-
struction industry [5], garments [6], dental and medical care products and equipment
[4, 7], automobiles and robots [8], military supplies [9], and electronics [10]. In 2020
alone, the global spending on 3D printing systems and related equipment was valued
at 16 billion U.S. dollars and is predicted to grow at a rate of 26.4% in the coming
years, with a projected revenue of approximately 40 billion U.S. dollars in 2024 [11].
Advances in additive manufacturing (often referred to as “3D printing”) tech-
nologies have greatly impacted the field of microfluidic device fabrication over the
past decade. One particular class of 3D printing, namely stereolithography, and its
variants has particular appeal for microfluidic manufacturing due to its ability to
create objects with small feature size and high resolution. In this chapter, we consider

Lubna Shahzadi, Australian Centre for Research on Separation Science (ACROSS), University of
Tasmania, Hobart, Australia; Interdisciplinary Research Center in Biomedical Materials, COMSATS
University Islamabad, Lahore Campus, Pakistan
Feng Li, Fernando Maya Alejandro, Michael C. Breadmore, Australian Centre for Research on
Separation Science (ACROSS), University of Tasmania, Hobart, Australia
Stuart C. Thickett, School of Natural Sciences (Chemistry), University of Tasmania, Hobart,
Australia

https://doi.org/10.1515/9783110570588-004
136 Lubna Shahzadi et al.

the underlying chemistry of resins for stereolithography in addition to the optical

properties of both the resin and the light source with a specific view to successfully
printing microfluidic devices consisting of enclosed channels with small cross-
sectional area. The main advantages and disadvantages of stereolithography, relative
to other 3D printing techniques, are addressed in addition to how the material proper-
ties of the final printed object can be tuned through resin additives such as nanoparti-
cle fillers or precursors, in addition to multi-material printing. Lastly, the performance
and application of printed devices is discussed.

4.2 Stereolithography
Stereolithography (SLA) is one of the earliest 3D printing techniques developed by
Charles Hull in 1986. It is a process in which photocurable materials are used and
products are made from a 3D model, layer-by-layer [12, 13]. The printer cures several
2D layers one upon the other, giving rise to a 3D object. SLA is particularly versatile
among all AM techniques due to the freedom of design, accuracy and the scale at
which the structures can be built; that is, at sub-micron dimensions [2]. The tech-
nique allows greater control over features and dimensions of the printing object. It
is different from conventional milling or cutting as the part is made layer-by-layer
with photopolymers, in an additive fashion.
The process begins with creating a three-dimensional sketch of the desired
product in the form of a computer-aided design (CAD). These can be designed using
different software such as AutoCAD, Autodesk or SOLIDWORKS, and an STL (stereo-
lithography tessellation language) or AMF (additive manufacturing) file is gener-
ated [14]. Some printer manufacturing companies offer specialized software for CAD
design. These programs convert CAD 3D models into individual layers and produce
an STL format, which is sent to the printer to build the product.
In this one-step fabrication method, a 3D model is prepared from a photo-resin.
The photo-resin is generally a mixture of epoxide or acrylate-based prepolymers, a pho-
toinitiator along with other additives. A programmed laser periodically scans the sur-
face of the resin to initiate polymerization and cure a patterned 2D layer. The liquid
resin mixture solidifies upon light exposure and the process is known as photocuring
or photopolymerization [8]. The printing typically takes place on a metallic platform,
which is immersed in liquid resin. The depth of the platform immersion corresponds to
the height of layer in the STL file, thus defining the outer dimensions of each 2D layer
of the final 3D model. The platform repeats its movement into and out of the resin.
With each immersion, a 2D layer is built and finally a 3D structure is produced [15].
After completion of printing, the object is washed to remove any unreacted
resin. A post-printing treatment of heating or further photo-curing is sometimes em-
ployed to improve the mechanical properties of the printed part. In addition to the
 Chapter 4 Resin design in stereolithography 3D printing for microfluidic applications 137

monomer and photoinitiator, resins also typically contain a stabilizer and a UV ab-
sorber/photo-blocker to adjust the polymerization depth [16]. The resolution of the
final printed part is determined by different variables such as light intensity, curing
time per layer and printing speed [17]. For high-resolution prints, photon flux, used
during the polymerization process, is also regulated. The high resolution of SLA is
the main characteristic that makes it distinct from other AM techniques.

4.2.1 Top-down and bottom-up printing configurations

There are two main types of SLA printing based on the system configuration. They
are referred to as top-down and bottom-up approaches. The difference between the
two approaches is the movement of the build platform after a layer is cured. In the
top-down system, the platform remains below the surface of the resin. As a layer is
cured, the platform moves a step down towards the base of the resin tank to allow
the liquid resin to fill in for the next layer to polymerize (Figure 4.1(a)).
In the bottom-up method, the base of the resin tank is transparent to let light
pass through the window. The platform resides one cure depth away from the base
of the resin tank. The light is irradiated from the bottom to polymerize the resin and
the platform then moves upwards, away from the base of the resin tank. Subse-
quently, more liquid resin flows in to coat the built object and enable polymeriza-
tion of the next layer [18] (Figure 4.1(b)). In the bottom-up approach, the printing
parts are exposed to greater mechanical forces, as each printing layer has to be sep-
arated from the base plate (usually glass), after the curing of that layer. However,
this approach has some advantages over the top-down approach: it requires smaller
resin volumes and the curing layer is not directly in contact with air, minimizing
inhibition due to oxygen.

4.2.2 Laser stereolithography (laser-SLA)

Laser-SLA is also known as vector-based stereolithography, but often simply re-

ferred to as SLA. A thin layer of unpolymerized resin is cured by scanning a laser
on the surface. Typically, the wavelength of this laser is in the near-UV region.
The x-y movement and the speed of the laser are controlled by two galvanometers
in addition to an optical system. A schematic diagram of a typical laser-SLA is
shown in Figure 4.1; it can function either via top-down or bottom-up approach.
Standard SLA systems are typically more expensive than other AM printers, for
example, extrusion-based printers, but they can give printing resolution as low as
10 μm [2].
To achieve high resolution in SLA, several factors need to be considered. For
higher z-resolution, the manner in which the laser is scanned across the entire
138 Lubna Shahzadi et al.

Figure 4.1: Schematic diagram of the SLA printing system: (a) Top-down approach (b) Bottom-up
approach.

layer is critical, in addition to precise stage movement and an optimized resin com-
position. For x-y resolution, the geometry of the laser beam and the movement of
the mirror galvanometers play important roles. Similarly, the scanning speed of the
laser and the diameter of laser spot also control both the vertical and lateral resolu-
tion by impacting the cure depth and width of the incident laser lines [19]. Laser-
SLA has been widely exploited to fabricate objects of great complexity and high
resolution for various applications [20, 21].

4.2.3 Digital light processing

Digital light processing (DLP) is one of the emerging techniques of SLA that offers
higher resolution than traditional SLA [22]. In contrast to a traditional laser
 Chapter 4 Resin design in stereolithography 3D printing for microfluidic applications 139

scanning SLA system, the entire print layer is exposed at once to the light from the
DLP projector (Figure 4.2). This simultaneous projection also greatly reduces the
printing time, providing a significant advantage for DLP over traditional SLA print-
ing. Most DLP systems follow a bottom-up printing approach, therefore, requiring
reduced resin volumes [18]. The projection of light is controlled by a digital mirror
device (DMD), which is the key component of a DLP system. It consists of an array
of mirrors that can be rotated to an on and off state independently and each mirror
symbolizes a pixel. The control over the projection light due to DMD ensures higher
accuracy and resolution of DLP systems [23]. With DLP setups, researchers have re-
ported a resolution of 25 μm [24]; composite resin with ceramic particles has been
reported to achieve lateral resolutions of 40 μm [25].
Although DLP systems have advantages of speed and resolution, these sys-
tems are not without their limitations. DLP is ideal for printing sharp corners, but
for a curved surface, the finished prints have a saw-tooth type of surface rough-
ness [25]. Secondly, the DLP systems are more suitable for printing small objects
with high resolution. The pixel size needs to be decreased when looking for higher
resolution with the aid of projection optics. As the digital mirror device has lim-
ited number of mirrors, it results in the shrinkage of the image and reduction of
the build space. Large parts are therefore printed at a lower resolution than small
ones [26].

Figure 4.2: Schematic diagram for DLP printing set-up.

140 Lubna Shahzadi et al.

4.2.4 Continuous light interface production

Continuous light interface production (CLIP) is a technique recently introduced by

Tumbleston et al. [27]. The printing set-up uses the same light projection set-up as
that of DLP. However, contrary to DLP and SLA systems, the printing does not rely
on a layer-by-layer fabrication; instead, the presence of oxygen is exploited as a po-
lymerization inhibitor. The introduction of an oxygen-permeable glass window and
oxygen permeable fluoropolymer at the floor of the resin tank creates a “dead
zone” in the uncured liquid resin (Figure 4.3). A thin layer of resin, between the vat
floor and the building platform, remains liquid at all times as the oxygen is more
present in this dead zone compared to free radicals generated by decomposition of
the photoinitiator. Printing starts only when there is insufficient oxygen to prevent
polymerization. Because the printed layer is not adjacent to the tank window, there
are no adhesion forces that need to be broken and the printed layer can be continu-
ously drawn out of the liquid resin, creating viscous flow to enable fresh resin to
flow into the dead zone. The end result is a layerless and monolithic fabrication,
and, thus, the printed part has improved mechanical properties relative to DLP [28].
In traditional SLA systems, laser scanning, movement of platform and refilling of
resin are separate discrete steps. As a result, there is a significant time period be-
tween each step, during which no actual printing takes place. In CLIP printing, the
mechanism still utilizes laser light to initiate polymerization, but instead of printing
each layer step-by-step, the resin gets continuously cured and, therefore, the wast-
age of time between individual steps is avoided. The technique has made the print-
ing time up to 100 times speedier than traditional printing systems [27].

Figure 4.3: Schematic diagram for CLIP printing set-up.

 Chapter 4 Resin design in stereolithography 3D printing for microfluidic applications 141

4.2.5 Volumetric photopolymerization

With the exception of CLIP, an issue associated with current 3D printing technologies
is the slow printing speed, more specifically with respect to printing in a layer-by-
layer format. Volumetric stereolithography is an approach to address this issue, as it
fabricates 3D objects as a unit operation. It is a relatively new additive manufacturing
technology, first developed by Shusteff et. al. in 2017 [29]. They developed a printing
system by the superposition of patterned optical fields from three orthogonal beams
projected into a photosensitive resin and various 3D structures were fabricated using
this approach within 1–10 s, without the requirement of any supporting structures.
Inspired by the working principle of image reconstruction procedures of com-
puted tomography (CT) that is widely used in medical imaging and non-destructive
testing, Kelly and co-workers developed a volumetric additive manufacturing ap-
proach called computed axial lithography (CAL) for 3D printing at high speed [30].
The system consists of a DLP projector and a rotating photocurable resin container.
During printing, the DLP projector projects computed intensity-modulated images
in a time-sequence related to the rotation rate of the photocurable resin container.
This results in each image projection propagating through the material from a dif-
ferent angle, selectively solidifying the resin within a contained volume. The devel-
oped system was able to fabricate features as small as 0.3 mm and also for various
centimeter-scale objects within 30–120 s. A similar system was also developed by
Loterie et.al. (Figure 4.4), where an integrated feedback system was combined with
the printing system to accurately control the photopolymerization kinetics over the
entire build volume, enabling the printing resolution to be improved to 80 μm posi-
tive and 500 μm negative features in less than 30 s [31].
Van der Laan and co-workers developed a two-color photopolymerization method
for volumetric printing. A resin containing camphorquinone (CQ)/ethyl 4-(dime-
thylamino) benzoate (EDAB) and butyl nitrite (BN) as initiator and inhibitor was
used; UV light and blue light independently activated the initiator and inhibitor.
By positioning the UV and blue light projectors perpendicularly for photoinhibi-
tion and photoinitiation, the system allowed for the fabrication of objects by volu-
metric photopolymerization, by patterning the bulk resin [32]. Recently, Li et al.
also demonstrated a dual-wavelength photopolymerization for volumetric addi-
tive manufacturing [33]. Different from the previous dual-wavelength approach
where the two projectors project static irradiation patterns, a multistep volumetric
printing was developed that involves a dynamic control of the projection patterns of
both UV and blue light projectors to enable the printing of more complex structures.
 142
Lubna Shahzadi et al.

Figure 4.4: Experimental setup for high-resolution tomographic printing. Reproduced with permission from [31]. Copyright 2020, Nature Publishing
Group.
Chapter 4 Resin design in stereolithography 3D printing for microfluidic applications 143

4.2.6 Advantages and disadvantages of SLA

As mentioned earlier, SLA has the highest resolution among all available AM tech-
niques. While other techniques can reach a resolution of 50–200 μm, SLA printers
can easily print features as small as 20 μm [34]. Traditional manufacturing methods
such as molding and machining are examples of subtractive processes in which
complex shapes are created by removal of excessive material. The performance and
machining of these methods are well-understood and controlled; however, these
techniques lack the ability to fabricate complex internal structures. On the other
hand, SLA techniques build the structures layer-by-layer, so the size and intricate
design of the product can be precisely controlled with minimal material waste. It is
particularly useful for manufacturing complex biomedical designs and devices. SLA
printing is a remarkable combination of a flexible method and high-functioning
products [35]. SLA allows the fabrication of complex products that would otherwise
need assembly of multiple parts if manufactured traditionally.
With respect to microfluidic device manufacturing, there are numerous advan-
tages with respect to using SLA. SLA printing offers the construction of robust,
high-throughput designs; for example, multiple identical products can be printed
for parallel experiments or numerous microfluidic devices with different test param-
eters can be printed concurrently with advanced printing set-ups. Minimizing
manufacturing errors between devices is an advantage that SLA provides, which is
not possible with conventional manufacturing approaches. Further, the ease of
sharing and exchanging device design via CAD or other design files enables re-
searchers in different labs around the world to reproduce, without variation, the
same devices and without manufacturing difficulties [36].
It is also important to acknowledge the challenges and limitations associated
with SLA-based techniques. There are a relatively limited number of commercially
available SLA resins, meaning that materials choice is potentially a significant limi-
tation. Traditional SLA printers can cure only a single material at a time, which en-
sures that multi-material printing is an active research challenge. The resultant
prints can be brittle and lack the strength and/or functionality to be used as fully
functional part in an integrated device and so are often considered only as concep-
tual prototypes rather than a functional component. Such problems limit the wide
industrial applications of these printed parts and materials. To overcome this chal-
lenge, additives such as nanoparticles, fibers and inorganic frameworks have been
added to polymers to improve the mechanical properties of these products [37].
Many commercially available resins result in cured objects that have poor sta-
bility against commonly used organic solvents and aqueous media. They may swell
in organic or aqueous solvents, which can cause flow or blockages in narrow chan-
nels. Absorption and adsorption are other concerns about the surface properties of
these printed devices. With respect to printing analytical devices, the polymer can
144 Lubna Shahzadi et al.

potentially absorb and/or adsorb the analyte under investigation, thus reducing the
concentration of analyte and thereby altering the detected signal [38].
Another consideration with respect to 3D printing of microfluidics is that the
resulting 3D-printed part can have some flaws that were not anticipated in the de-
signed product as developed using CAD software. CAD programs develop objects
that are a combination of solid geometries and boundaries between these geome-
tries. The transfer of a CAD design into a 3D printed object sometimes results in er-
rors and defects, in particular with curved surfaces [39].
Polydimethylsiloxane (PDMS) devices are optically transparent and are pre-
dominantly used in the development of optical devices, contrary to available photo-
polymers. Although “clear” 3D-printing materials are available, they are typically
translucent/semi-transparent and sometime require post-print processing such as
polishing. But, it can only be done to outer surfaces, and small channels and com-
plex designs cannot be polished. The problem restricts the use of these materials to
print optical devices.

4.3 Features of photocurable resins for SLA

4.3.1 Photocurable monomers and oligomers

Photocurable resins are generally mixtures of multi-functional monomers or oligomers

that are polymerized and solidify when irradiated by UV light such as the projector of
a 3D printer. According to an industrial survey, almost 50% of the industrial proto-
types in the 3D printing market are developed using photocurable resins [24]. In
SLA-based 3D printing, the resin system also contains a photoinitiator as well as a
number of additives such as diluents, surfactants, photo-blockers, stabilizers and
fillers (Figure 4.5) [40].The chemical structure and formulations for most of com-
mercially available resins are confidential but typically consist of multifunctional
acrylates and/or methacrylates [41]. In some reports, a combination of different
commercially available resins has also been employed to achieve specific proper-
ties in a printed item [27]; however, most commercial resins cannot be used for
multiple applications. There is, therefore, an active area of research with regards
to the development of new monomers and crosslinkers for specific applications
that surpass the properties of existing commercial resins.
In the first SLA formulation used by Charles Hull, urethane diacrylate with a
small portion of acrylic acid were used as monomers. A 350 W mercury lamp with
an irradiance of 1 W cm−2 was employed as a source of light projection. Benzophe-
none and methyl ethyl hydroquinone (MEHQ)/triallyl phosphate were utilized as
photoinitiator and inhibitor, respectively, to avoid the premature polymerization of
the precursor [24]. Since this first demonstration of SLA, there has been significant
 Chapter 4 Resin design in stereolithography 3D printing for microfluidic applications 145

Figure 4.5: The components of SLA resins.

development in resin chemistry with respect to the monomers used, photoinitiators,

photo-blockers and other additives present. These are discussed in the following
sections.

4.3.2 (Meth)acrylate-based resin systems

Currently, (meth)acrylates are the most widely used photopolymers in SLA. A typi-
cal photocurable (meth) acrylate system consists of multifunctional monomers; that
is, di, tri or tetra-functional (meth)acrylates. These resins undergo rapid radical
chain photopolymerization at room temperatures. The rapid polymerization of
acrylates (compared to methacrylates) allows faster building times and is thus gen-
erally considered to be well-suited for most commercial and custom-made 3D print-
ers [42]. These systems have been employed to print materials like shape-memory
polymers [43], inorganic ion-based composite materials [44], UV-curable elastomers
[45], 3D printable biomaterials [46], etc. A mixture of different (meth)acrylates is
often used to tune the mechanical properties and thermal resistance of the printed
part. The curing of methacrylates is slower than acrylates but they are far less toxic
than acrylates, and are therefore more frequently used in dental restorative materi-
als [47]. The most frequently used (meth)acrylate monomers and crosslinkers
(Figure 4.6) are polyethylene glycol diacrylate (PEGDA) [21, 48], triethylene glycol
dimethacrylate (TEGMA) [49, 50], urethane dimethacrylate (UDMA) [51], DGEBA
146 Lubna Shahzadi et al.

Figure 4.6: Commonly used (meth)acrylates-based monomers/oligomers in 3D printing.

based acrylates [49, 50, 52] and trimethylolpropane triacrylate (TTA) [27, 28]. More
details on the recent progress of novel 3D printable photopolymerizable biomacro-
molecules are available in Chapter 5.
In the curing process of acrylates and methacrylates, non-uniform polymer net-
works can potentially form as a result of the high resin viscosity and restricted dif-
fusion of the reacting species [53]. Monomer diffusion is greatly reduced, resulting
in the double bond conversion within a given printed layer being well below 100%.
This, in part, results in the brittle nature and mediocre mechanical properties of
most acrylate-based materials. This limitation can be fixed by using more flexible
starting monomers [54] or via the incorporation of inorganic fillers into the resin.
The resultant printed objects can have improved glass transition temperature,
Young’s modulus and surface hardness [55].
It is worth noting that acrylate and methacrylate-based resins are susceptible to
inhibition by oxygen [56]. Researchers have tried to overcome this problem through
the inclusion of different additives, for example, tertiary amines [57], when using
open resin tank 3D printing systems. The addition of tertiary amines, however, can
result in the unwanted discoloration of printed objects [58].

4.3.3 Epoxy/cationic resins

Cationic/epoxy resins were first developed in 1970s, primarily to overcome the lim-
itations of (meth)acrylate resins. These resins can be cured either by light or heat,
depending on the nature of the additives in the resin mixture. Thermally curable
 Chapter 4 Resin design in stereolithography 3D printing for microfluidic applications 147

epoxy resins are more common and are mostly used to increase the toughness of
the resulting polymer [59]. Some of the most popular commercial monomers in the
epoxy family are digylcidyl ether derivatives of bisphenol A (DGEBA) with differ-
ent chain lengths and molecular weights phenol formaldehyde, 3,4-epoxycyclo-
hexylmethyl-3,4-epoxycycloheane carboxylate (EPOX) and various glycidyl imides
(Figure 4.7). The viscosity of the monomer mixture can be adjusted using various
reactive diluents such as alkyl glycidyl ethers.

Figure 4.7: Commonly used epoxy monomers used in cationic 3D printing.

The photopolymerization of epoxy resins is typically initiated via a photoactivated

cationic initiator such as sulphonium or iodonium salts [60, 61]. The first cationic
photoinitiators were aryl iodonium salts with non-nucleophilic counterions such as
BF4¯ or PF6¯ [62]. These thermally stable compounds, when irradiated with UV
light, decompose into a mixture of cations, radical cations and radical intermedi-
ates. Traditionally, photocurable epoxy resins were utilized in coatings, but now
they have also been explored in 3D printing [63]. A significant advantage in the use
of epoxy resins is their low shrinkage upon polymerization, compared to acrylate-
based resins, which is due to chain propagation occurring via sequential ring-
opening reactions of epoxides. The reactivity of an epoxide depends on the structure
of the epoxide molecule and is potentially tuneable; cycloaliphatic epoxides tend to
react most rapidly. Oxetanes are also often used in commercial 3D printing systems
because of their fast polymerization time, low shrinkage and relatively reduced mois-
ture uptake compared to analogous epoxy polymers [64].
The interest in using these epoxy resin is due to their low shrinkage (~3%) com-
pared to acrylate-based resins. Theoretically, cationic polymerization progresses in
a chain-growth mechanism where more crosslinking points are available at the
polymer backbone, resulting in a more brittle polymer. To avoid over crosslinking
and brittleness, polyesters, and polyols, in low concentrations, are used widely
[65]. To improve the mechanical properties of these materials, resin systems have
been developed with more than one kind of monomer and with varying reactivities.
148 Lubna Shahzadi et al.

In this manner, the properties and polymerization of the resulting 3D printed item
can be regulated [66].
The crosslinking density of the polymer plays a significant role in determining
its mechanical properties. Therefore, the scope of the dual-cure formulations has
also been explored [67]. In these formulations, monomers with both acrylate and
epoxide functional groups are exploited for polymerization. Thus, the polymeriza-
tion can proceed through, both, cationic or free-radical mechanism [68]. In such
cases, a combination of cationic and Type I photoinitiators has been employed [24].
Further, a combination of acrylate and epoxy resins has been investigated to get 3D
printable photopolymers with tuneable crosslinking density, mechanical properties
and polymerization rate [69].

4.3.4 Thiol-ene/yne resins

Acrylic and epoxy resins are the most common commercial resins currently avail-
able. However, the fast development of 3D printing technologies and their rapid ad-
vancement in widespread applications require the development of more innovative
and multifunctional materials. The reactions of carbon-carbon double bonds with
thiol groups are well-known in chemistry [70] and polymers of various architectures
can be formed via the step-growth reaction of multi-functional vinyl compounds
(“enes”) and multifunctional thiols (Figure 4.8). These reactions can follow a free-
radical or Michael-addition mechanism, depending upon the catalyst/initiator [71],
and are often referred to, generically, as “thiol-ene” reactions. Alkyl thiols can also
react with carbon-carbon triple bonds, resulting in “thiol-yne” photocurable resins.
After the addition of the first thiol group to the alkyne molecule, vinyl sulfide is
generated, which undergoes another thiol addition and subsequently, a polymer
with higher crosslinking density is produced, compared to the equivalent thiol-ene
resins. As a result, thiol-yne based polymers have higher glass transition tempera-
tures and higher modulus than thiol-ene based products [72].
One of the major advantages of thiol-ene resins compared to acrylic resins is
improved oxygen inhibition [73]. Furthermore, these resins have lower volumetric
shrinkage than their acrylate counterparts, primarily due to the comparatively high
conversion gel point [74]. They also exhibit better biocompatibility than acrylate-
based polymer networks [75]. These characteristics make thiol-ene systems attrac-
tive candidates for 3D printing applications. Thiol-ene based systems have been
exploited to prepare biocompatible hydrogels [76] as well as materials for optical
applications [77]. Some of the more typical thiol monomers for 3D printing are pen-
taerythritoltetrakis(3-mercaptopropionate) [78], trimethylolpropanetris(3-mercapto-
propionate) [79] and tris[2-(3-mercaptopropionyloxy)ethyl]isocyanurate [80].
Chapter 4 Resin design in stereolithography 3D printing for microfluidic applications 149

Figure 4.8: Recently used thiol and ene/yne monomers in SLA 3D printing.

While there are several advantages with regard to thiol-ene/yne resin systems,
there are also some concerns associated with these resins that deter their use in 3D
printing applications, such as poor shelf life and unpleasant smell. They can also
have weak mechanical properties due to the flexible thioether linkages that result in
low modulus [81]. There are solutions to these two drawbacks; the polymer modulus
can be increased by adding an acrylate monomer to thiol-ene resin [82], facilitating
acrylate homopolymerization. The shelf life of these resins can also be improved
with the addition of a radical stabilizer [83].

4.3.5 Photoinitiators

Photoinitiators (PIs) are key components of the resin that absorb light of a particu-
lar wavelength and facilitate the formation of reactive intermediates to commence
polymerization. Most monomers and crosslinkers cannot initiate polymerization on
their own and therefore require an external photoinitiator. The reactive species
150 Lubna Shahzadi et al.

generated by the initiator (typically free radicals or cations) react with the monomer
present and facilitate either chain growth (propagation) or step-growth. The photoini-
tiator is selected depending on the nature and chemistry of the precursors, in addi-
tion to the light source of the 3D printer. The type and quantity of the photoinitiator
greatly affect a number of aspects of the printed object, namely reaction kinetics,
polymer conversion, light dosage required for the polymerization, cross-linking den-
sity and, hence, the mechanical properties [84].
The predominant polymerization mechanism in SLA is free radical chain growth
polymerization [85], which primarily consists of initiation, propagation, termination
and chain transfer. As the monomers are multi-functional, gelation of the resin takes
place that finally converts each layer into a solid structure through cross-linking.
The solidification of the polymer takes place in two steps. The first step is gelation, in
which the precursors are converted into a gel-like polymeric matrix of, essentially,
infinite molecular weight. The viscosity of the resin increases significantly due to the
high crosslinking density. This step is kinetically controlled. The second step is vitrifi-
cation, in which the viscosity reaches a certain point and the rubbery gel matrix
transforms into a glassy state. The overall rate of reaction decreases significantly.
Therefore, this vitrification step is a diffusion-controlled step. This step also governs
the final conversion degree of the polymer. The SLA polymers are generally brittle
and rigid, which can be due to the fast reaction pace in the gelation step and/or non-
uniform crosslinking of polymer because of inhomogeneous diffusion of the mono-
mer in the vitrification stage [3].
Broadly, radical photoinitiators can be divided two classes based on their reac-
tion mechanism, Norrish Type I and Type II [85] (Figure 4.9). The radical generation
in these systems takes place by α-cleavage and H-abstraction, respectively [71].
Type I initiators are single molecules that undergo α-cleavage when irradiated with
light at a specific wavelength [86]. The molecule breaks into two separate radicals,
of which one is typically active as an initiating radical. As α-cleavage of different

Figure 4.9: Some examples of Type I and Type II photoinitiators, recently used in literature with
their respective λmax.
 Chapter 4 Resin design in stereolithography 3D printing for microfluidic applications 151

molecules require a specific wavelength of UV light, therefore, various Type I initia-

tors have distinct UV-Vis range and intensity to work. The n — π* transitions in
these initiators are fairly low energy, so they are frequently used in commercial SLA
resins. The class includes benzil ketals, hydroxyacetophenone, benzoin and various
phosphine oxides [85]. The photocleavage of a common Type I photoinitiator is
given in Scheme 4.1.

Scheme 4.1: Photocleavage of Type I photoinitiator.

Type II photoinitiators are two-component systems: a light absorbing molecule and

a co-initiator or synergist. The molecule that absorbs light does not undergo cleav-
age, instead, forms an excited triplet state that can facilitate hydrogen atom transfer
from the co-initiator (Scheme 4.2). The result of this reaction are two species con-
taining a free radical, however, it is the radical derived from the co-initiator that
facilitates polymerization. The most commonly used initiators are camphorqui-
nones, benzophenones and thioxanthones, while tertiary amines and thiols gener-
ally constitute the co-initiator part of the system. As a bimolecular process, Type II
initiator systems are typically slower than Type I initiators but provide a broader
range of polymerization wavelengths. Recent progresses in the development of
novel one-photon and two-photon photoinitiators for 3D printing are demonstrated
in Chapter 1 and Chapter 2.

Scheme 4.2: Photocleavage of Type II photoinitiator.

4.3.6 Absorbers and photo-blockers

A critical component of SLA resins for printing of objects with small features at
high resolution is the photo-blocker or absorber or dye. As the name suggests,
photo-blockers absorb a significant amount of the incident light and, subsequently,
restrict the penetration depth (Dp) of light through the resin. This, consequently,
152 Lubna Shahzadi et al.

constrains polymerization closer to the resin surface and reduces the thickness of
the printed objects. It is discussed in further detail in Section 4. The control over
penetration depth is particularly important to print intricate designs and geome-
tries. It avoids over-curing of the resin in the z-direction and thus improves the
overall resolution of the printed part [87]. The chemical structures of some absorb-
ers for SLA resin formulations are shown in Figure 4.10.

Figure 4.10: Photo-absorbers/photo-blockers for SLA photo-resins.

Benzotriazole derivatives, pyrenes and substituted anthracenes are some of the

most commonly used photo-blockers in SLA processes [88]. Reducing the penetra-
tion depth allows for thinner printing layers, more control over z-resolution and
thus more intricate structures can be printed that would otherwise not be possible.
Researchers have shown that addition of a photo-blocker such as 2-ethyl-9,10-
dimethoxyanthracene (EDMA) at a loading of 2 wt % reduced the penetration depth
by almost a factor of four [24]. Similarly, Sudan Orange and stilbene derivatives
such as 1,4-bis(2-dimethylstyryl)benzene (BMSB) have also largely been used as
photo-blockers with a variety of resin formulations [89]. To reach microfluidic flow
channels as small as 18 μm × 20 μm, Gong et. al. employed 2-nitrophenyl phenyl sul-
fide (NPS) as UV absorber [34], which is discussed in Section 4.4.1. Recent advance-
ments in the use of dyes/absorbers in light-induced 3D printing are described in
Chapter 3.

4.3.7 Diluents and inhibitors

The viscosity of the photo-resin plays an important role in the successful printing
of an object. Resins with too high viscosity or with high loading of fillers lack the
flow and wetting behavior that are essential to achieve high resolution. The in-
crease in viscosity changes the flow dynamics of the resin and interferes with the
wetting mechanism of the substrate, thus increasing the mechanical force re-
quired for the elevation of the build platform. Therefore, diluents are sometimes
 Chapter 4 Resin design in stereolithography 3D printing for microfluidic applications 153

required to modify the viscosity of the resin. For high-resolution prints, the dilu-
ent must be reactive with the precursors, but should remain non-reactive under
storage conditions. For example, 1,6-hexanediol diacrylate can be used to consid-
erably reduce the viscosity of a resin when ceramic fillers are used in the formula-
tion [90].
Another factor that increases the viscosity of the resin and its poor storage life
is premature gelation of precursors. Inhibitors are used in resin formulations to pre-
vent premature gelation. Butylated hydroxytoluene (BHT), pyrogallol and methoxy
hydroquinone (MEHQ) are the most commonly used inhibitors (Figure 4.11) and are
generally added to the resin at a concentration of 50 to 200 ppm [91]. For cationic/
epoxy polymers, benzyl-N,N’-dimethylamine (BDMA) is used as an inhibitor at a
concentration of 5 to 250 ppm with 1 wt.% photoacid generator. BDMA is weak base
that efficiently neutralizes the radical cations [92].

Figure 4.11: Commonly used radical and cationic

inhibitors.

4.4 SLA for printing of microfluidic devices

4.4.1 Resin optical properties

Given that additive manufacturing via SLA can be described as a series of sequen-
tial photopolymerization processes built up in a series of layers, the kinetics of pho-
topolymerization can be employed to both understand and control the curing of an
SLA resin. This is critical to achieve small printed dimensions in the z-direction, in-
cluding the ability to generate closed channels with small cross-sectional area that
are needed for the preparation of microfluidic devices.
As addressed in Section 3, commercial or bespoke SLA resins typically consist
of a multifunctional monomer (such as a multifunctional acrylate or methacrylate)
or monomer mixture, photoinitiator, as well as photo-blocker to limit the penetra-
tion depth of incident light into the resin. The well-known description of free-
radical photopolymerization [93, 94] potentially applies in this context. At a given
depth z in a photocurable resin, the local rate of photopolymerization Rp (assuming
a steady-state radical flux) is given by
qffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffi qffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffi
αI
Rp = kp ½M ϕ αIz′ ½In = kp ½M ϕ 0′ ½Ine − α½Inz (4:1)
kt E kt E
154 Lubna Shahzadi et al.

where ɸ is the quantum yield for initiation, kp the propagation coefficient of the
monomer, kt the rate coefficient for bimolecular radical termination, [M] the mono-
mer concentration, [In] the photoinitiator concentration, I0 the incident light intensity
at the surface of the resin, α (=ln(10)ε) the molar absorption coefficient of the photo-
initiator at the wavelength of the projector, E’ the energy of a photon (=NAhc/λ).
In eq. (4.1) it is assumed that incident light is only absorbed by the photoinitiator;
this absorption results in an exponential decay in the light intensity as a function
of resin depth z via the Beer-Lambert law (Iz = e − α½Inz ). The attenuation of light in-
tensity can be amplified further through the addition of a relevant photo-blocker,
which results in the following light intensity profile:
 
P
− αi ½ci z (4:2)
Iz = I0 e i

X
where Iz is the light intensity at depth z and αi ½ci the sum of the attenuation co-
efficients (i.e. the products of molar absorption i coefficients and concentration) of
all absorbing species in the resin; this quantity is typically dominated by the ab-
sorption due to photo-blocker. The exponential decay described in eq. (4.2) can be
incorporated into eq. (4.1), generating a highly non-linear polymerization profile
throughout the resin; the result is a constraint of the cured polymer close to the
resin surface. Inspection of eq. (4.1) reveals a 0.5 reaction order dependence with
respect to the incident light intensity and the photoinitiator concentration.
It is worth noting that the kinetic model described by eq. (4.1) provides an ana-
lytic solution in a relatively simple case, based on several approximations. These
include: neglecting the presence of diatomic oxygen as inhibitor (and its potential
diffusion throughout an SLA resin) [95], assuming a uniform distribution of photo-
initiator throughout the resin [96], no consideration for potential resin photobleach-
ing [97, 98], neglecting thermal and mass transfer effects [99] and the potential role
of primary (initiator-derived) radical termination [100]. Including these terms typi-
cally requires a numerical solution to the various rate equations that govern photo-
polymerization. Furthermore, given most monomers used in SLA are multifunctional
(meth)acrylates, it is more appropriate to describe the monomer concentration [M] as
the vinyl group concentration ([C=C]) and the rate of polymerization linked to the
consumption of vinyl groups as a function of the position within the resin. This is
particularly relevant for “thiol-ene” resins where the homopolymerization of the
(meth)acrylate component can occur in parallel with the step-growth polymerization
process between thiol and -ene groups [101, 102].
The resulting analytical or numerical solution to the rate of photopolymerization
yields a description of the fractional conversion of monomer to polymer p as a function
of both time and depth z within the resin. For multifunctional monomers such as those
used in SLA, there is a critical conversion pc that results in the gelation of the resin,
effectively solidifying the resin at that specific depth once the critical conversion is
 Chapter 4 Resin design in stereolithography 3D printing for microfluidic applications 155

reached. The value of pc is ≪ 1 for multifunctional monomers and is well-modeled by

the gelation in the absence of cyclisation [103–105], namely:

pc = 1
f −1 (4:3)

where f is the functionality of the monomer; that is, the number of reactive species
each monomer can react with. For a multifunctional (meth)acrylate with n vinyl
groups, f = 2 n and therefore, pc is as low as 0.14 for a tetraacrylate-based resin. The
photocuring of a resin via SLA, therefore, results in the growth of a solidified layer
as a function of time, equivalent to a frontal polymerization from the incident sur-
face growing in the z-axis. The cured layer thickness increases logarithmically with
time (see Figure 4.12); Cabral et al. [106] describe the cured object layer thickness zp
via the following relationship:

1.0 4
10
d 1/μ∞
conversion %
0.8
Conversion fraction, ϕ

5 3
Height (mm)

0.6
0 2
0 2 4 6
0.4 depth (mm)

time 1
0.2
τ 1/μ0
c 0
0.0
0 2 4 6 8 0.001 0.1 10 1000
Depth (mm) Time (s)

Figure 4.12: Photocuring of resins for stereolithography. (Left panel): evolution of the fractional
conversion of monomer to polymer as a function of z-depth into the resin. (Right panel): Height of
the cured object as a function of time, assuming a non-constant resin attenuation coefficient at
zero (μ0) and full (μ∞) conversion of monomer to polymer. Adapted with permission from [106].
Copyright 2004, American Chemical Society.

 
zp = μ
1 ln t
Tc (4:4)

where μ
is the arithmetic mean of the attenuation coefficients of the resin in both the
unpolymerized and fully polymerized states, t the curing time and Tc defined as an
induction time, related to the critical conversion pc via the following relationship:
− lnð1 − pc Þ
Tc = KI0 (4:5)
156 Lubna Shahzadi et al.

where I0 is the incident light intensity and K is a “growth rate” such that the product
KI0 has units of s−1. The induction time Tc represents the time to successfully cure the
surface layer (i.e. z = 0); for curing times t < Tc, the critical conversion pc has not been
reached anywhere within the resin; in the context of SLA 3D printing, this represents
the minimum curing time per layer. The parameter K in eq. (4.5) is a function of the
various polymerization rate coefficients such as those detailed in eq. (4.1). Lee et al.
[107] used the steady-state solution to eq. (4.1) to develop an analytical solution for
cure depth versus time in photocured 2,2-bis-4-[2-hydroxy-3-(methacryloxy)pro-
poxy]phenyl-propane (Bis-GMA) resins; their work linked underlying polymeriza-
tion rate coefficients to Tc with good qualitative agreement to experiment. Boddapati
et al. [108, 109]. developed an extended model to describe the induction time Tc
for the photopolymerization of trimethylolpropane triacrylate (TMPTA) that ac-
counted for diffusion of oxygen through the resin (and potential termination of
polymeric radicals via reaction with oxygen) that showed excellent agreement with
experimental rate and induction time data, as measured by FTIR spectroscopy and
microrheology [110].
The cured layer thickness zp, as described in eq. (4.4), is often expressed in
terms of the photocuring energy instead of time, proposed by Jacobs as the ‘stan-
dard design curve’ for stereolithography [111]:
 
zp = ha ln EEc (4:6)

where E is the energy (typically expressed in units of mJ cm−2) supplied by the light
source at the resin surface and Ec is defined as the critical energy to successfully
cure the polymer immediately at the interface (i.e. z = 0). The quantity ha in eq. (4.6)
is often referred to as the “penetration depth” and is defined as the inverse of the
attenuation coefficient μ
defined in eq. (4.4). Mathematically, the quantity ha repre-
sents the distance into the resin where the light intensity has decreased to e−1 of its
initial value. In its simplest form, ha can be calculated as:

ha = P 1α ½c (4:7)
i i i

The use of energy (as opposed to time) to model the photocuring depth enables experi-
ments to be standardized across light sources of different intensities. Experimental val-
ues of ha and Ec were determined by Bennett [112] by measuring the thickness of
various photocuring resins via a combination of caliper measurements, profilometry
and confocal scanning microscopy at both 365 nm and 405 nm (see Figure 4.13; in this
Figure the symbol Cd is used in place of zp). As an alternative, Gong and co-workers
developed a 3D-printed object consisting of a series of pillars to directly measure ha
and Tc by monitoring the thickness of a photocured membrane atop each pillar as a
function of time [89]. For proprietary resins, where the underlying chemistry is undis-
closed, it is difficult to compare experimental ha and Ec/Tc values with those predicted
 Chapter 4 Resin design in stereolithography 3D printing for microfluidic applications 157

1,400
PR48 - 365

1,200 PR48 - 405

VeroWhitePlus - 365
1,000 VeroWhitePlus - 405
Formlabs Clear - 365
800 Formlabs Clear - 405
Cd (μm)

VeroClear - 365
600 VeroClear - 405
TangoBlackPlus - 365
400
TangoBlackPlus - 405

200

0
1 10 100 1,000 10,000
E0 (mJ/cm2)

Figure 4.13: Variation of cured object thickness as a function of laser light exposure for various resins
at 365 nm and 405 nm incident light. Reproduced with permission from [112]. Copyright 2017, Elsevier.

from theory. However, good agreement is regularly seen when there is good spectral
overlap between the light source and photoinitiator (and photo-blocker) for specifically
designed resin chemistry [34, 89].
The various descriptions of photocuring described above demonstrate that the
growth of a cured layer with time is related to the optical properties of the resin
(specifically the photo-blocker concentration and the light penetration into the
resin), the nature of the light source and the chemical rate coefficients that control
the photopolymerization process. Each printed layer in SLA can be treated as an
individual photocuring process. For the design of enclosed flow channels with
small dimensions by SLA that have relevance in microfluidics, a detailed under-
standing of curing rates is essential. Specifically, prolonged exposure times (per
layer) and large light penetration depths into the bulk resin significantly influence
the minimum feature size that is achievable. This is discussed in detail in work
from Nordin’s group [34, 89], where the light “dose” (equivalent to the energy E in
eq. (4.6), the product of the light intensity at a given depth multiplied by the poly-
merization time) was considered as a function of polymerization depth z and curing
time. For decreasing values of ha (i.e. increasing the photo-blocker concentration),
the curing time must increase to achieve the equivalent polymerization depth,
however, this also increases the inhomogeneity of the light dose across the cured
layer. In the reverse situation, increasing ha values leads to shorter curing times
158 Lubna Shahzadi et al.

but results in significant light penetration into the resin and potential overcuring –
beyond the target layer thickness.
The optical model towards resin chemistry [89] describes the process of devel-
oping a microfluidic device (i.e. an open channel enclosed in a cured polymeric ma-
trix) by SLA (see Figure 4.14). Specifically, the optical properties of the resin and
the print times per layer are evaluated so that the resin located at the position of
the targeted channel remains “uncured” – that is, the resin in this layer receives a
total dose (amount of energy) that is less than the critical energy to achieve a fully
solidified polymer layer. Post-printing, this enables uncured resin to be removed by
rinsing with solvent, yielding the desired structure. The critical balance that must
be accounted to print an enclosed channel is that cured layers printed subsequent
to the channel do not absorb all of the incident light exposure, potentially resulting
in unwanted resin curing in the channel. This can be modeled by considering the
normalized dose of light that the nth layer in a printed object receives (Ωn(γ,t1)),
where γ is the normalized depth in the resin (γ = z/z1 where z1 is the printed layer
thickness) and t1 the print time per layer:

Ωn ðγ, t1 Þ = τ1 eð − ½ðn + 1Þ − γζ 1 Þ for γ ≤ n + 1; = 0 otherwise (4:8)

Where τ1 is the normalized print time per layer (≡t1/Tc) and ζ1 is the normalized
layer thickness (≡z1/ha). The total dose Ω at a given position γ within the resin is
thus equal to the sum of the doses across all layers, that is,
NP
−1
Ωðγ, t1 Þ = δn Ωn (4:9)
n=0

where δn is the Kronecker delta and is used to describe the position of an embed-
ded channel across a specific number of layers (i.e. δn = 0 to form a channel or
void). A layer is considered cured if the total dose Ω is > 1 across the entire layer
thickness and uncured if Ω < 1. An example is shown in Figure 4.15, where a 12-
layer printed object is modeled with a targeted flow channel in layers 5 and 6.
Here, the normalized dose within layers 5 and 6 is not < 1, indicating that layer 6
would receive sufficient light exposure to be partially cured. One option to ad-
dress this issue is to reduce ha (achieved by increasing the photo-blocker concen-
tration), however, this is not possible with commercial resin formulations as ha
is fixed.
Increasing the print layer thickness is an alternative approach towards mini-
mizing unwanted curing in previously printed layers that contain voids, however,
this can lead to other issues with the final printed product. The variation in incident
light exposure across larger print layers is significantly greater than for smaller
print layers (Figure 4.15), which can result in poor inter-layer adhesion and incon-
sistent mechanical properties between layers. This balance between potential over-
curing and layer inhomogeneity results in significantly different print qualities for
 Chapter 4 Resin design in stereolithography 3D printing for microfluidic applications 159

Printed Next y x
device layer
(a) z
Layer 0
1 Build table
2 Resin

Resin
tray
Light

Layer 0 (b) y x
1
2
3 z
4
5

Layer 0
1
2 (c) y x
3
4
5 z
6
7 Trapped
8 resign
9

9
8
7
6 (d) Designed
5 channel
4
3
2 z
1
Layer 0
x y

Figure 4.14: Schematic of printed microfluidic device via stereolithography. A channel is included
within layer 5 (image B above) and then enclosed through printing layers 6–9. Assuming no
polymerization of the resin trapped within the channel, washing of the object post-printing and
removal of the resin reveals the desired structure. Reproduced with permission from [89].
Copyright 2015, Royal Society of Chemistry.

enclosed flow channels; it was shown that the smallest print layer thickness tested
(10 μm) resulted in channels with smooth walls with no obvious serration due to
individual print layers (see Figure 4.16). The height of successfully fabricated en-
closed channels was shown to be ~ 3.5 ha for PEGDA/Sudan I resins, where ha > 50 μm,
160 Lubna Shahzadi et al.

(a) Layer 0 exposure Layer 2 exposure Layer 4 exposure

Layer 1 exposure Layer 3 exposure Total exposure
6
Layer
index: 0 1 2 3 4
5
Normalized dose, Ω(z,τl)

τl = 2.0
4 ha = 72.5
ζl = 0.69
3

0
0 50 100 150 200 250
z ( μm)

(b) 6
0 1 2 3 4 5 6 7 8 9 10 11
5
Single layer parameters
Normalized dose, Ω(z,τl)

ζl = 0.69
4 τl = Ωfront = 2.0
Ωback = 1.0

0
0 2 4 6 8 10 12
𝛾

Figure 4.15: Optical dose applied to an SLA resin under a variety of conditions. Panel (a): variation
of normalized dose across a printed object consisting of 5 layers. A normalized dose of 1
represents a fully cured layer. (b) Modeled normalized dose across a 12-layer object with channel
in layers 5 and 6. In this case, overcuring has occurred as the normalized dose is > 1 within layer 6.
(c) Effect of varying print layer thickness for printing a 200 μm channel. Reproduced with
permission from [89]. Copyright 2015, Royal Society of Chemistry.

and ~ 5.5 ha for resins with ha < 40 μm. An optimized PEGDA resin was developed incor-
porating 3 % w/w NPS as photoblocker (ha = 8 μm) enabled the successful printing of
channels of height 2.3 ha (18 μm); the cross-sectional area of these channels was as
small as 18 μm × 20 μm [34].
 Chapter 4 Resin design in stereolithography 3D printing for microfluidic applications 161

(c) 6
zl = 50.00 μm
ζl = 1.50
5 τl = 4.47
zl = 25.00 μm
Normalized dose, Ω(z,τl)

ζl = 0.75
4 τl = 2.11
zl = 10.00 μm
ζl = 0.30
3 τl = 1.35

2 ha = 33.4 μm
L = 200.0 μm
L/ha = 5.99
1

0
0 100 200 300 400 500
z (μm)

Figure 4.15 (continued)

Figure 4.16: Optical microscopy images demonstrating the impact of print layer thickness on the
quality of enclosed channels (200 μm high, 135 μm wide) within a PEGDA resin using Sudan I as
photoblocker. Left to right: 50 μm, 25 μm and 10 μm print layers respectively. Reproduced with
permission from [89]. Copyright 2015, Royal Society of Chemistry.

4.4.2 Materials considerations

One of the main limitations for expanding the scope of 3D printing applications by
stereolithography (SLA) in the field of microfluidics is the limited selection of mate-
rials available to date. While the amount of novel materials for fused deposition
modeling is increasing at a faster pace, the limited amount of materials that can be
photopolymerized is the main bottleneck in 3D printing by SLA. The development
of novel photopolymerizable formulations will be critical for the advancement of 3D
printing by SLA as a technique for the fabrication of microfluidic devices. The de-
velopment of novel materials for 3D printing by SLA has been focused towards ob-
taining 3D printed parts with improved mechanical properties, chemical stability
and functionality.
Typical resin formulations for SLA 3D printing are based on acrylate monomers
and oligomers, which result in polymers with a relatively limited stability at higher
162 Lubna Shahzadi et al.

temperatures or when exposed to organic solvents. This will limit the application of
microfluidics based on such materials for applications required high temperature, the
use of organic solvents typically used in analytical sample preparation, or liquid chro-
matographic techniques. These disadvantages greatly limit the application of this ad-
ditive manufacturing technique for the fabrication of devices for analytical separation
science. This limitation is circumvented easily in FDM 3D printing by fabricating fila-
ments using more resistant polymers such as polyether ether ketone (PEEK).
In SLA 3D printing, a route to circumvent this limitation is the 3D printing of
composites based on the dispersion of ceramic particles on an acrylate-based resin
[113]. A critical parameter in the photopolymerization of composite resins is the stabil-
ity of the photopolymerizable resin containing a high load of the ceramic particles, as
the aggregation or precipitation of these particles will lead to a final 3D printed part
with a non-homogeneous distribution of the ceramic particles. This was achieved by
dispersing amorphous silica nanoparticles (40 nm, mean diameter) in the polymeri-
zation mixture. The polymerization mixture consists mostly on the monomer hydrox-
yethyl methacrylate (HEMA). The use of this hydrophilic monomer enabled the
dispersion of a high load of silica nanoparticles without requiring further additives.
Using SLA, 3D printed parts based on the previous composite resins were fabricated.
The initial 3D printed part was thermally debound, removing the polymer matrix by
thermal decomposition. The resulting part was sintered at 1,300 °C to obtain high-
quality fused silica glass with no remnants of porosity or cracks.
An alternative to the addition of silica nanoparticles to the polymerization mix-
ture is the use of photosensitive methylsilsesquioxane preceramic polymers. In this
case, the resin was prepared from a commercially available methylsilsesquioxane
resin (SILRES MK, Wacker‐Chemie GmbH, Nuenchritz, Germany) [114]. The 3D
printed parts, based on this polymerization mixture containing SILRES, were con-
verted to SiOC by pyrolysis at 1,000 °C under nitrogen atmosphere. In a different
example, a UV-curable siloxane formulation was prepared from (mercaptopropyl)
methylsiloxane and vinylmethoxysiloxane combined with a photoinitiator that is
active at 405 nm [115]. After carbonization at 1,000 °C, the preceramic polymer is
converted to an amorphous silicon oxycarbide containing sulphur.
While glass is the preferred materials for microfluidics because of its chemical
and thermal stability, fluorinated polymers such as polytetrafluoroethylene (PTFE)
also have high chemical and thermal stability. PTFE is not a polymer suitable for
stereolithography. However, PTFE nanoparticles can be dispersed in a photocurable
resin and the resulting composite resin can be 3D printed by stereolithography
[116]. In a similar procedure, as mentioned for the 3D printing of glass devices, the
PTFE/polymer 3D printed part was sintered at 370–400 °C. A limitation here is that
the resulting PTFE-based 3D printed devices would be non-transparent, making it
difficult for certain types of applications such as UV-vis monitoring.
Highly fluorinated perfluoropolyether (PFPE) methacrylates are interesting
alternatives for transparent and chemically resistant microfluidic chips. A new
Chapter 4 Resin design in stereolithography 3D printing for microfluidic applications 163

coating material, named Fluoropor, has been developed by the photopolymeriza-

tion of a PFPE‐methacrylate using cyclohexanol as non-solvent and a fluorinated al-
cohol as an emulsifying agent. Fluoropor has been shown to be an interesting
candidate for 3D printing of chemically resistant parts since it can be printed using
benchtop SLA 3D printers [117]. The developed formulation was used to 3D print mi-
crofluidic chips with a minimal cross-sectional area of 600 µm for monolithic embed-
ded channels and 200 µm for open channels. In addition, the PFPE-methacrylate
used in this application showed a transmittance of above 70% for light with wave-
lengths between 520–900 nm. It also showed a high chemical resistance against or-
ganic solvents. As a proof of concept of microfluidic application, a gradient generator
was 3D printed (Figure 4.18). The channels of the gradient generator have a width
and height of 800 µm (Figure 4.17(a, b)), or 600 µm (Figure 4.17(c, d)).

Figure 4.17: 3D printed microfluidic gradient generator based on PFPE-methacrylate. Scale bars: (a)
and (c), 2 mm; (b) and (d), 500 µm. Reproduced with permission from [117]. Copyright 2018, MDPI.

The development of simple and efficient strategies to SLA 3D print devices with high
resolution in glass, or fluorinated polymers will be critical for the development of ro-
bust devices for microfluidic applications.
164 Lubna Shahzadi et al.

4.4.3 Examples and performance of printed objects

SLA 3D printing is currently the best option for microfluidics fabrication owing to
its high printing resolution compared to FDM and unlike inkjet printers such as Pol-
yJet, it does not require supporting material, which normally takes days and weeks
to remove from inside the microchannel. Channel dimensions and optical transpar-
ency of the printed device are two important factors affecting the performance of
the SLA printed microfluidics. Shallan and co-workers directly 3D printed microflui-
dic devices with cross sectional area of 250 µm, with an SLA 3D printer for the first
time and used these 3D printed devices for various applications including micro-
mixing, gradient generation and isotachophoresis [118]. The minimum microchan-
nel size fabricated with a commercially available SLA 3D printer and resins was
154 µm by Macdonald et al. [119].
Nordin’s group has done tremendous work in improving the SLA printing reso-
lution for truly microfluidic devices fabrication through optimizing the resin formu-
lations and the printer light source using a customized printing setup. Using their
customized SLA printer and resin formulations, microfluidic channels with cross
sections as small as 18 µm × 20 µm were successfully created as shown in Figure 4.18
[34]. This printer, with high printing resolution, has also been used for other appli-
cations such as for microchip electrophoresis of preterm birth markers detection
with the limit of detection in the high pM to low nM range. This was the first report
of the creation of microchip electrophoresis devices with < 50 µm cross-sectional di-
mensions by 3D printing [120].
Optical detection is the most common detection method for microfluidics, so
the optical transparency property of the printed device can affect the detection sig-
nificantly. Both Rapp’s and Folch’s groups have achieved SLA printing with highly
transparent materials such as glass and PDMS, respectively. Glass is one of the ma-
terials used in the early stages of microfluidic research, given its unmatchable opti-
cal transmittance, high chemical and thermal resistance, and low non-specific
adsorption that enable its wide application in optical detection and capillary chro-
matography. Kotz et.al developed an SLA-based approach for transparent glass 3D
printing with photocurable silica nanocomposite at a resolution of 60 μm and sur-
face roughness of 2 nm. The printing process is shown in Figure 4.19 [113].
More recently, Kotz and co-workers fabricated hollow 3D microchannels in glass
indirectly by combining sacrificial template replication with a photopolymerization
process [121]. PDMS is currently the most widely used material for microfluidics fabri-
cation due to its high transparency, biocompatibility and gas permeability. However,
PDMS molding is a manual procedure and requires tedious and time-consuming as-
sembly steps. Femmer et al. developed an SLA approach for printing PDMS through
the use of a PDMS copolymer functionalized with 7–9 mol % pendant methacrylate
groups as the main resin component with ethyl (2,4,6-trimethylbenzoyl) phenyl phos-
phinate (TPO-L) as photoinitiator and Orasol Orange as photo-blocker [122]. This
 Chapter 4 Resin design in stereolithography 3D printing for microfluidic applications 165

Figure 4.18: (a) Primary and additional edge exposure patterns for a single layer containing a flow
channel. (b) Channel narrowing for 2% NPS resin for additional edge exposure. The build layer
thickness is 8.3 μm and the designed flow channel height is 25 μm. (c) Same as (b) except for 3%
NPS resin with 6 μm layers and a designed flow channel height of 18 μm. (d), (e) measured channel
width and height, respectively, as a function of edge exposure time. Reproduced with permission
from [34]. Copyright 2017, Royal Society of Chemistry.

resin system enabled the printing of a cross-flow gas-liquid PDMS membrane with
the connectors integrated as part of the print. Bhattacharjee and co-workers used a
similar approach for the 3D printing of PDMS microfluidics [123]. The resins consisted
of a functionalized 3-methacryloxypropyl-PDMS copolymer as well as methacryloyl-
terminated PDMS as monomers in addition to TPO-L and isopropylthioxanthone
 166
Lubna Shahzadi et al.

Figure 4.19: (a) Ultraviolet-curable monomer mixed with amorphous silica nanopowder is structured in a
stereolithography system. The resulting polymerized composite is turned into fused silica glass through thermal
debinding and sintering (scale bar, 7 mm). (b, c), Examples of printed and sintered glass structures: Karlsruhe Institute
of Technology logo (b; scale bar, 5 mm) and pretzel ((c); scale bar, 5 mm). (d), Demonstration of the high thermal
resistance of printed fused silica glass (scale bar, 1 cm). The flame had a temperature of about 800 °C. Reproduced with
permission from [113]. Copyright 2017, Nature Publishing Group.
Chapter 4 Resin design in stereolithography 3D printing for microfluidic applications 167

(ITX) as photoinitiators and photo-blockers, respectively. The resins were polymer-

ized with a 385 nm light source to produce transparent microfluidic devices with
cross sectional areas of 300 µm × 500 µm for use in mammalian cell culture.
Another interesting application of SLA printing in microfluidics is the fabrication
of integrated devices to increase the functionality of the devices [124]. Multimaterial
3D printing is the most ideal approach for integrating microfluidics fabrication, but it
is difficult to easily achieve multimaterial printing with SLA printer. Currently, SLA
printing integrated microfluidics is mainly through single material printing, which
can be obtained by combining the 3D geometry and intrinsic material properties. Rog-
ers and co-workers fabricated a microfluidic device with integrated pneumatic valves
capable of operating for 800 actuations. The device was SLA printed with a custom-
ized resin and integrated with a 3D printed 100 μm membrane as part of the device.
Due to the flexibility of the thin membrane, an external pressure caused the localized
deflection and was used for sealing the inlet and outlet openings, effectively clos-
ing the valve. The valve was opened when the external pressure was released and
the membrane returned to its original position [125]. Modular microfluidic devices
were also fabricated with SLA printing – Bhargava and co-workers fabricated inte-
grated microfluidic devices including a gradient generator, microdroplet generator
and optical droplet sensing system by assembling discrete reconfigurable compo-
nents printed with a SLA printer [126]. Yuen also presented a ‘Plug-n-plug’ modular
microfluidic system with multiple microfluidic components, including a motherboard
with fluidic interconnects, fittings, and fluidic inserts fabricated with SLA printing in-
dividually [127].

4.5 Conclusions and perspectives

Over the past decade, SLA based techniques have shown to be an exceptionally ex-
citing approach in the fabrication of microfluidic devices with tailored feature size,
materials properties and functionality. Compared to the historical state of the art of
PDMS molding to produce devices, the move towards printed objects via CAD de-
sign represents a significant step towards standardized printing with increased re-
producibility. While the learning curve can be potentially steep for researchers
entering the field, the wealth of printed designs that are freely available for down-
load should encourage more non-specialists in the field.
Compared to other 3D printing techniques, SLA is particularly appealing for mi-
crofluidic applications, given the ability to print features with small size at high reso-
lution. One major drawback has been the relatively limited choice of materials for
printing. However, this is an active area of research through the development of new
resin chemistries amenable to SLA, specifically with a view towards improved me-
chanical properties and chemical resistance. An ongoing challenge is the fabrication
168 Lubna Shahzadi et al.

of a fully integrated device with parts that require different materials properties as
opposed to separate part fabrication across multiple steps. Multi-material 3D printing
can potentially address this question. However, it is a technique that is still in its in-
fancy and challenges exist with respect to the printer setup to successfully print dif-
ferent resins (or different resin components) in one print. We consider this an
exciting area of research in the near future.
Great advances have been made in the successful printing of devices with en-
closed channels via SLA-based 3D printing. This has been made possible through
the rational control of light penetration through the resin by specific additives such
as photo-blockers and a systematic understanding of print parameters such as print
layer thickness and print time. Such understanding has enabled SLA to move from
being only able to print millifluidic devices to those truly in the microfluidic range.
Other approaches to control or constrain the printed object thickness at the resin
interface present opportunities to push the capabilities of SLA even further in the
coming years.

References
[1] Chapiro, M. Current achievements and future outlook for composites in 3D printing, Reinf
Plast, 2016, 60, 372–375.
[2] Wang, X., Jiang, M., Zhou, Z., Gou, J., Hui, D. 3D printing of polymer matrix composites: A
review and prospective, Composites Part B Eng, 2017, 110, 442–458.
[3] Manapat, J. Z., Chen, Q., Ye, P., Advincula, R. C. 3D printing of polymer nanocomposites via
stereolithography, Macromol Mater Eng, 2017, 302, 1600553.
[4] Stansbury, J. W., Idacavage, M. J. 3D printing with polymers: Challenges among expanding
options and opportunities, Dent Mater, 2016, 32, 54–64.
[5] Buchanan, C., Gardner, L. Metal 3D printing in construction: A review of methods, research,
applications, opportunities and challenges, Eng Struct, 2019, 180, 332–348.
[6] Sanatgar, R. H., Campagne, C., Nierstrasz, V. Investigation of the adhesion properties of
direct 3D printing of polymers and nanocomposites on textiles: Effect of FDM printing
process parameters, Appl Surf Sci, 2017, 403, 551–563.
[7] Morris, V. B., Nimbalkar, S., Younesi, M., McClellan, P., Akkus, O. Mechanical properties,
cytocompatibility and manufacturability of chitosan: PEGDAHybrid-Gel Scaffolds by
stereolithography, Ann Biomed Eng, 2017, 45, 286–296.
[8] Lee, J.-Y., An, J., Chua, C. K. Fundamentals and applications of 3D printing for novel
materials, Appl Mater Today, 2017, 7, 120–133.
[9] Peels, J. 3D Printing in the Military. 3d Print 2017.
[10] Crivello, J. V., Reichmanis, E. Photopolymer materials and processes for advanced
technologies, Chem Mater, 2014, 26, 533–548.
[11] Global 3D printing products and services market size from 2020 to 2024. Jul 23, 2020 ed.
United States of America: Statista, Inc, 2020.
[12] Campbell, T., Williams, C., Ivanova, O., Garrett, B. Could 3D printing change the world.
Technologies, Potential, and Implications of Additive Manufacturing, Atlantic Council,
Washington, DC. 2011.
Chapter 4 Resin design in stereolithography 3D printing for microfluidic applications 169

[13] Standard, A. ISO/ASTM 52900: 2015 Additive manufacturing-General principles-terminology.

ASTM F2792-10e1. 2012.
[14] Grimm, T. User’s guide to rapid prototyping, Society of Manufacturing Engineers, 2004. the
text.
[15] Truby, R. L., Lewis, J. A. Printing soft matter in three dimensions, Nature, 2016, 540, 371.
[16] Heller, C., Schwentenwein, M., Russmueller, G., Varga, F., Stampfl, J., Liska, R. Vinyl esters:
Low cytotoxicity monomers for the fabrication of biocompatible 3D scaffolds by lithography
based additive manufacturing, J Polym Sci A Polym Chem, 2009, 47, 6941–6954.
[17] Cho, Y. H., Lee, I. H., Cho, D.-W. Laser scanning path generation considering photopolymer
solidification in micro-stereolithography, Microsyst Technol, 2005, 11, 158–167.
[18] de Leon, A. C., Chen, Q., Palaganas, N. B., Palaganas, J. O., Manapat, J., Advincula, R. C. High
performance polymer nanocomposites for additive manufacturing applications, React Funct
Polym, 2016, 103, 141–155.
[19] Schmidleithner, C., Kalaskar, D. M. Stereolithography. IntechOpen; 2018.
[20] Elomaa, L., Pan, -C.-C., Shanjani, Y., Malkovskiy, A., Seppälä, J. V., Yang, Y. Three-
dimensional fabrication of cell-laden biodegradable poly (ethylene glycol-co-depsipeptide)
hydrogels by visible light stereolithography, J Mater Chem B, 2015, 3, 8348–8358.
[21] Palaganas, N. B., Mangadlao, J. D., de Leon, A. C. C., Palaganas, J. O., Pangilinan, K. D., Lee,
Y. J., et al. 3D printing of photocurable cellulose nanocrystal composite for fabrication of
complex architectures via stereolithography, ACS Appl Mater Interfaces, 2017, 9,
34314–34324.
[22] Zhu, W., Qu, X., Zhu, J., Ma, X., Patel, S., Liu, J., et al. Direct 3D bioprinting of prevascularized
tissue constructs with complex microarchitecture, Biomaterials, 2017, 124, 106–115.
[23] Katal, G., Tyagi, N., Joshi, A. Digital light processing and its future applications, Int J Sci Eng
Res Publ, 2013, 3, 1997–2004.
[24] Ligon, S. C., Liska, R., Stampfl, J., Gurr, M., Mülhaupt, R. Polymers for 3D printing and
customized additive manufacturing, Chem Rev, 2017, 117, 10212–10290.
[25] Hatzenbichler, M., Geppert, M., Seemann, R., Stampfl, J. Additive manufacturing of
photopolymers using the Texas Instruments DLP lightcrafter. Emerging Digital Micromirror
Device Based Systems and Applications V: International Society for Optics and Photonics;
2013, 86180A.
[26] Baumgartner, S., Pfaffinger, M., Busetti, B., Stampfl, J. Comparison of dynamic mask-and
vector-based ceramic stereolithography. Proceedings of the 41st International Conference on
Advanced Ceramics and Composites Hoboken, Wiley: Wiley Online Library, 2018, 163–173.
[27] Tumbleston, J. R., Shirvanyants, D., Ermoshkin, N., Janusziewicz, R., Johnson, A. R., Kelly, D.,
et al. Continuous liquid interface production of 3D objects, Science, 2015, 347, 1349–1352.
[28] Janusziewicz, R., Tumbleston, J. R., Quintanilla, A. L., Mecham, S. J., DeSimone,
J. M. Layerless fabrication with continuous liquid interface production, Proc Natl Acad Sci,
2016, 113, 11703–11708.
[29] Shusteff, M., Browar, A. E., Kelly, B. E., Henriksson, J., Weisgraber, T. H., Panas, R. M., et al.
One-step volumetric additive manufacturing of complex polymer structures, Sci Adv, 2017, 3,
eaao5496.
[30] Kelly, B. E., Bhattacharya, I., Heidari, H., Shusteff, M., Spadaccini, C. M., Taylor,
H. K. Volumetric additive manufacturing via tomographic reconstruction, Science, 2019, 363,
1075–1079.
[31] Loterie, D., Delrot, P., Moser, C. High-resolution tomographic volumetric additive
manufacturing, Nat Commun, 2020, 11, 1–6.
170 Lubna Shahzadi et al.

[32] Van Der Laan, H. L., Burns, M. A., Scott, T. F. Volumetric photopolymerization confinement
through dual-wavelength photoinitiation and photoinhibition, ACS Macro Lett, 2019, 8,
899–904.
[33] Li, F., Thickett, S. C., Maya, F., Doeven, E. H., Guijt, R. M., Breadmore, M. C. Rapid Additive
Manufacturing of 3D Geometric Structures via Dual-Wavelength Polymerization, ACS Macro
Lett, 2020, 9(10), 1409–1414.
[34] Gong, H., Bickham, B. P., Woolley, A. T., Nordin, G. P. Custom 3D printer and resin for
18 μm × 20 μm microfluidic flow channels, Lab Chip, 2017, 17, 2899–2909.
[35] Zarek, M., Mansour, N., Shapira, S., Cohn, D. 4D printing of shape memory-based
personalized endoluminal medical devices, Macromol Rapid Commun, 2017, 38, 1600628.
[36] Erkal, J. L., Selimovic, A., Gross, B. C., Lockwood, S. Y., Walton, E. L., McNamara, S., et al. 3D
printed microfluidic devices with integrated versatile and reusable electrodes, Lab Chip,
2014, 14, 2023–2032.
[37] Han, Y., Wang, F., Wang, H., Jiao, X., Chen, D. High-strength boehmite-acrylate composites
for 3D printing: Reinforced filler-matrix interactions, Compos Sci Technol, 2018, 154,
104–109.
[38] Ma, Y., Dong, J., Bhattacharjee, S., Wijeratne, S., Bruening, M. L., Baker, G. L. Increased
protein sorption in poly (acrylic acid)-containing films through incorporation of comb-like
polymers and film adsorption at low pH and high ionic strength, Langmuir, 2013, 29,
2946–2954.
[39] Gao, W., Zhang, Y., Ramanujan, D., Ramani, K., Chen, Y., Williams, C. B., et al. The status,
challenges, and future of additive manufacturing in engineering, Comput-Aided Des, 2015,
69, 65–89.
[40] Xing, J.-F., Zheng, M.-L., Duan, X.-M. Two-photon polymerization microfabrication of
hydrogels: An advanced 3D printing technology for tissue engineering and drug delivery,
Chem Soc Rev, 2015, 44, 5031–5039.
[41] Zhang, J., Xiao, P. 3D printing of photopolymers, Polym Chem, 2018, 9, 1530–1540.
[42] Zheng, X., Smith, W., Jackson, J., Moran, B., Cui, H., Chen, D., et al. Multiscale metallic
metamaterials, Nat Mater, 2016, 15, 1100.
[43] Zarek, M., Layani, M., Cooperstein, I., Sachyani, E., Cohn, D., Magdassi, S. 3D printing of
shape memory polymers for flexible electronic devices, Adv Mater, 2016, 28, 4449–4454.
[44] Palaganas, J., de Leon, A. C., Mangadlao, J., Palaganas, N., Mael, A., Lee, Y. J., et al. Facile
preparation of photocurable siloxane composite for 3D printing, Macromol Mater Eng, 2017,
302, 1600477.
[45] Patel, D. K., Sakhaei, A. H., Layani, M., Zhang, B., Ge, Q., Magdassi, S. Highly stretchable
and UV curable elastomers for digital light processing based 3D printing, Adv Mater, 2017,
29, 1606000.
[46] Stassi, S., Fantino, E., Calmo, R., Chiappone, A., Gillono, M., Scaiola, D., et al. Polymeric 3D
printed functional microcantilevers for biosensing applications, ACS Appl Mater Interfaces,
2017, 9, 19193–19201.
[47] Moszner, N., Salz, U. New developments of polymeric dental composites, Prog Polym Sci,
2001, 26, 535–576.
[48] Warner, J., Soman, P., Zhu, W., Tom, M., Chen, S. Design and 3D printing of hydrogel
scaffolds with fractal geometries, ACS Biomater Sci Eng, 2016, 2, 1763–1770.
[49] Al Mousawi, A., Garra, P., Sallenave, X., Dumur, F., Toufaily, J., Hamieh, T., et al. π-
conjugated dithienophosphole derivatives as high performance photoinitiators for 3D
printing resins, Macromolecules, 2018, 51, 1811–1821.
 Chapter 4 Resin design in stereolithography 3D printing for microfluidic applications 171

[50] Al Mousawi, A., Garra, P., Schmitt, M., Toufaily, J., Hamieh, T., Graff, B., et al. 3-hydroxyflavone
and N-phenylglycine in high performance photoinitiating systems for 3D printing and
photocomposites synthesis, Macromolecules, 2018, 51, 4633–4641.
[51] Yue, J., Zhao, P., Gerasimov, J. Y., van de Lagemaat, M., Grotenhuis, A., Rustema‐Abbing, M.,
et al. 3D‐printable antimicrobial composite resins, Adv Funct Mater, 2015, 25, 6756–6767.
[52] Credi, C., Fiorese, A., Tironi, M., Bernasconi, R., Magagnin, L., Levi, M., et al. 3D printing of
cantilever-type microstructures by stereolithography of ferromagnetic photopolymers, ACS
Appl Mater Interfaces, 2016, 8, 26332–26342.
[53] Goodner, M. D., Bowman, C. N. Development of a comprehensive free radical
photopolymerization model incorporating heat and mass transfer effects in thick films, Chem
Eng Sci, 2002, 57, 887–900.
[54] Elliott, J. E., Lovell, L., Bowman, C. Primary cyclization in the polymerization of bis-GMA and
TEGDMA: A modeling approach to understanding the cure of dental resins, Dent Mater, 2001,
17, 221–229.
[55] Chiappone, A., Fantino, E., Roppolo, I., Lorusso, M., Manfredi, D., Fino, P., et al. 3D printed
PEG-based hybrid nanocomposites obtained by sol–gel technique, ACS Appl Mater
Interfaces, 2016, 8, 5627–5633.
[56] Yagci, Y., Jockusch, S., Turro, N. J. Photoinitiated polymerization: Advances, challenges, and
opportunities, Macromolecules, 2010, 43, 6245–6260.
[57] Mirle, S. K., Kumpfmiller, R. J. Photosensitive compositions useful in three-dimensional part-
building and having improved photospeed. Google Patents; 1995.
[58] Steinmann, B. Stereolithographic resins with high temperature and high impact resistance.
Google Patents; 2006.
[59] Bagheri, R., Marouf, B., Pearson, R. Rubber-toughened epoxies: A critical review, J Macromol
Sci, Part C: Polym Rev, 2009, 49, 201–225.
[60] Matsumura, S., Hlil, A. R., Lepiller, C., Gaudet, J., Guay, D., Shi, Z., et al. Ionomers for proton
exchange membrane fuel cells with sulfonic acid groups on the end groups: Novel branched
poly (ether− ketone) s, Macromolecules, 2008, 41, 281–284.
[61] Crivello, J. V. Design of photoacid generating systems, J Photopolym Sci Technol, 2009, 22,
575–582.
[62] Crivello, J. V. The discovery and development of onium salt cationic photoinitiators, J Polym
Sci A Polym Chem, 1999, 37, 4241–4254.
[63] Al Mousawi, A., Poriel, C., Dumur, F., Toufaily, J., Hamieh, T., Fouassier, J. P., et al. Zinc
tetraphenylporphyrin as high performance visible light photoinitiator of cationic
photosensitive resins for LED projector 3D printing applications, Macromolecules, 2017, 50,
746–753.
[64] Xu, J. Photo-curable resin composition. Google Patents; 2015.
[65] Steinmann, B., Schulthess, A. Liquid, radiation-curable composition, especially for
stereolithography. Google Patents; 1999.
[66] Lapin, S. C., Brautigam, R. J. Stereolithography using vinyl ether based polymers. Google
Patents; 1996.
[67] Xiao, P., Dumur, F., Frigoli, M., Tehfe, M.-A., Graff, B., Fouassier, J. P., et al. Naphthalimide
based methacrylated photoinitiators in radical and cationic photopolymerization under
visible light, Polym Chem, 2013, 4, 5440–5448.
[68] Cai, Y., Jessop, J. L. Decreased oxygen inhibition in photopolymerized acrylate/epoxide
hybrid polymer coatings as demonstrated by Raman spectroscopy, Polymer, 2006, 47,
6560–6566.
[69] Ohkawa, K., Saito, S. Resin Composition for Optical Modeling. Patent NumberEP 0360869.
1990.
172 Lubna Shahzadi et al.

[70] Kade, M. J., Burke, D. J., Hawker, C. J. The power of thiol‐ene chemistry, J Polym Sci A Polym
Chem, 2010, 48, 743–750.
[71] Ligon-Auer, S. C., Schwentenwein, M., Gorsche, C., Stampfl, J., Liska, R. Toughening of
photo-curable polymer networks: A review, Polym Chem, 2016, 7, 257–286.
[72] Fairbanks, B. D., Sims, E. A., Anseth, K. S., Bowman, C. N. Reaction rates and mechanisms for
radical, photoinitiated addition of thiols to alkynes, and implications for thiol− Yne
photopolymerizations and click reactions, Macromolecules, 2010, 43, 4113–4119.
[73] Husár, B., Ligon, S. C., Wutzel, H., Hoffmann, H., Liska, R. The formulator’s guide to anti-
oxygen inhibition additives, Prog Org Coat, 2014, 77, 1789–1798.
[74] McNair, O. D., Janisse, A. P., Krzeminski, D. E., Brent, D. E., Gould, T. E., Rawlins, J. W., et al.
Impact properties of thiol–ene networks, ACS Appl Mater Interfaces, 2013, 5, 11004–11013.
[75] Oesterreicher, A., Wiener, J., Roth, M., Moser, A., Gmeiner, R., Edler, M., et al. Tough and
degradable photopolymers derived from alkyne monomers for 3D printing of biomedical
materials, Polym Chem, 2016, 7, 5169–5180.
[76] Bertlein, S., Brown, G., Lim, K. S., Jungst, T., Boeck, T., Blunk, T., et al. Thiol–ene clickable
gelatin: A platform bioink for multiple 3D biofabrication technologies, Adv Mater, 2017, 29,
1703404.
[77] Kumpfmueller, J., Stadlmann, K., Li, Z., Satzinger, V., Stampfl, J., Liska, R. Two-photon-
induced thiol-ene polymerization as a fabrication tool for flexible optical waveguides, Des
Monomers Polym, 2014, 17, 390–400.
[78] Chen, L., Wu, Q., Wei, G., Liu, R., Li, Z. Highly stable thiol–ene systems: From their
structure–property relationship to DLP 3D printing, J Mater Chem C, 2018, 6, 11561–11568.
[79] Sycks, D. G., Wu, T., Park, H. S., Gall, K. Tough, stable spiroacetal thiol‐ene resin for 3D
printing, J Appl Polym Sci, 2018, 135, 46259.
[80] Mongkhontreerat, S., Öberg, K., Erixon, L., Löwenhielm, P., Hult, A., Malkoch, M. UV initiated
thiol–ene chemistry: A facile and modular synthetic methodology for the construction of
functional 3D networks with tunable properties, J Mater Chem A, 2013, 1, 13732–13737.
[81] Senyurt, A. F., Hoyle, C. E., Wei, H., Piland, S. G., Gould, T. E. Thermal and mechanical
properties of cross-linked photopolymers based on multifunctional thiol− urethane ene
monomers, Macromolecules, 2007, 40, 3174–3182.
[82] Hoyle, C. E., Lee, T. Y., Roper, T. Thiol–enes: Chemistry of the past with promise for the
future, J Polym Sci A Polym Chem, 2004, 42, 5301–5338.
[83] Belbakra, Z., Cherkaoui, Z. M., Allonas, X. Photocurable polythiol based (meth) acrylate
resins stabilization: New powerful stabilizers and stabilization systems, Polym Degrad Stab,
2014, 110, 298–307.
[84] Bail, R., Patel, A., Yang, H., Rogers, C., Rose, F., Segal, J., et al. The effect of a type I
photoinitiator on cure kinetics and cell toxicity in projection-microstereolithography,
Procedia CIRP, 2013, 5, 222–225.
[85] Bagheri, A., Jin, J. Photopolymerization in 3D printing, ACS Appl Polym Mater, 2019, 1,
593–611.
[86] Jasinski, F., Zetterlund, P. B., Braun, A. M., Chemtob, A. Photopolymerization in dispersed
systems, Prog Polym Sci, 2018, 84, 47–88.
[87] Hofstetter, C., Orman, S., Baudis, S., Stampfl, J. Combining cure depth and cure degree, a
new way to fully characterize novel photopolymers, Addit Manuf, 2018, 24, 166–172.
[88] Bail, R., Hong, J. Y., Chin, B. D. Effect of a red-shifted benzotriazole UV absorber on curing
depth and kinetics in visible light initiated photopolymer resins for 3D printing, J Ind Eng
Chem, 2016, 38, 141–145.
[89] Gong, H., Beauchamp, M., Perry, S., Woolley, A. T., Nordin, G. P. Optical approach to resin
formulation for 3D printed microfluidics, RSC Adv, 2015, 5, 106621–106632.
 Chapter 4 Resin design in stereolithography 3D printing for microfluidic applications 173

[90] Badev, A., Abouliatim, Y., Chartier, T., Lecamp, L., Lebaudy, P., Chaput, C., et al.
Photopolymerization kinetics of a polyether acrylate in the presence of ceramic fillers used in
stereolithography, J Photochem Photobiol A Chem, 2011, 222, 117–122.
[91] Messe, L., Chapelat, C. Curable composition. Google Patents; 2013.
[92] Melisaris, A. P., Renyi, W., Pang, T. H. Liquid, radiation-curable composition, especially for
producing flexible cured articles by stereolithography. Google Patents; 2002.
[93] Odian, G. Principles of polymerization, 4th edn, Wiley Interscience: Hoboken, New Jersey,
USA, 2004.
[94] Terrones, G., Pearlstein, A. J. Effects of optical attenuation and consumption of a
photobleaching initiator on local initiation rates in photopolymerizations, Macromolecules,
2001, 34, 3195–3204.
[95] Lin, J.-T., Liu, H.-W., Chen, K.-T., Cheng, D.-C. Modeling the kinetics, curing depth, and
efficacy of radical-mediated photopolymerization: The role of oxygen inhibition, viscosity,
and dynamic light intensity, Front Chem, 2019, 7, 760.
[96] Lin, J.-T., Wang, K.-C. Analytic formulas and numerical simulations for the dynamics of thick
and non-uniform polymerization by a UV light, J Polym Res, 2016, 23, 53.
[97] Miller, G. A., Gou, L., Narayanan, V., Scranton, A. B. Modeling of photobleaching for the
photoinitiation of thick polymerization systems, J Polym Sci A Polym Chem, 2002, 40,
793–808.
[98] Ivanov, V. V., Decker, C. Kinetic study of photoinitiated frontal polymerization, Polym Int,
2001, 50, 113–118.
[99] O’Brien, A. K., Bowman, C. N. Modeling thermal and optical effects on photopolymerization
systems, Macromolecules, 2003, 36, 7777–7782.
[100] Goodner, M. D., Bowman, C. N. Modeling primary radical termination and its effects on
autoacceleration in photopolymerization kinetics, Macromolecules, 1999, 32, 6552–6559.
[101] Cramer, N. B., Davies, T., O’Brien, A. K., Bowman, C. N. Mechanism and modeling of a thiol−ene
photopolymerization, Macromolecules, 2003, 36, 4631–4636.
[102] Cramer, N. B., Reddy, S. K., O’Brien, A. K., Bowman, C. N. Thiol−ene photopolymerization
mechanism and rate limiting step changes for various vinyl functional group chemistries,
Macromolecules, 2003, 36, 7964–7969.
[103] Flory, P. J. Molecular size distribution in three dimensional polymers. I. Gelation1, J Am Chem
Soc, 1941, 63, 3083–3090.
[104] Carothers, W. H. Polymerization, Chem Rev, 1931, 8, 353–426.
[105] Carothers, W. H. Polymers and polyfunctionality, Trans Faraday Soc, 1936, 32, 39–49.
[106] Cabral, J. T., Hudson, S. D., Harrison, C., Douglas, J. F. Frontal photopolymerization for
microfluidic applications, Langmuir, 2004, 20, 10020–10029.
[107] Lee, J. H., Prud’homme, R. K., Askay, I. A. Cure depth in photopolymerization: Experiments
and theory, J Mater Res, 2001, 16, 3536–3544.
[108] Boddapati, A., Rahane, S. B., Slopek, R. P., Breedveld, V., Henderson, C. L., Grover, M. A. Gel
time prediction of multifunctional acrylates using a kinetics model, Polymer, 2011, 52,
866–873.
[109] Boddapati, A. Modelling Cure Depth During Photopolymerization of Multifunctional Acrylates:
Georgia Institute of Technology; 2010.
[110] Slopek, R. P., McKinley, H. K., Henderson, C. L., Breedveld, V. In situ monitoring of
mechanical properties during photopolymerization with particle tracking microrheology,
Polymer, 2006, 47, 2263–2268.
[111] Jacobs, P. F. Rapid Prototyping and Manufacturing: Fundamentals of Sterolithography:
Society of Manufacturing Engineers; 1992.
174 Lubna Shahzadi et al.

[112] Bennett, J. Measuring UV curing parameters of commercial photopolymers used in additive

manufacturing, Addit Manuf, 2017, 18, 203–212.
[113] Kotz, F., Arnold, K., Bauer, W., Schild, D., Keller, N., Sachsenheimer, K., et al. Three-
dimensional printing of transparent fused silica glass, Nature, 2017, 544, 337–339.
[114] Zanchetta, E., Cattaldo, M., Franchin, G., Schwentenwein, M., Homa, J., Brusatin, G., et al.
Stereolithography of SiOC Ceramic Microcomponents, Adv Mater, 2016, 28, 370–376.
[115] Hundley, J. M., Eckel, Z. C., Schueller, E., Cante, K., Biesboer, S. M., Yahata, B. D., et al.
Geometric characterization of additively manufactured polymer derived ceramics, Addit
Manuf, 2017, 18, 95–102.
[116] Helmer, D., Voigt, A., Wagner, S., Keller, N., Sachsenheimer, K., Kotz, F., et al. Suspended
liquid subtractive lithography: One-step generation of 3D channel geometries in viscous
curable polymer matrices, Sci Rep, 2017, 7, 7387.
[117] Kotz, F., Risch, P., Helmer, D., Rapp, B. E. Highly fluorinated methacrylates for optical 3D
printing of microfluidic devices, Micromachines, 2018, 9, 115.
[118] Shallan, A. I., Smejkal, P., Corban, M., Guijt, R. M., Breadmore, M. C. Cost-effective three-
dimensional printing of visibly transparent microchips within minutes, Anal Chem, 2014, 86,
3124–3130.
[119] Macdonald, N. P., Cabot, J. M., Smejkal, P., Guijt, R. M., Paull, B., Breadmore,
M. C. Comparing microfluidic performance of three-dimensional (3D) printing platforms, Anal
Chem, 2017, 89, 3858–3866.
[120] Beauchamp, M. J., Nielsen, A. V., Gong, H., Nordin, G. P., Woolley, A. T. 3d printed
microfluidic devices for microchip electrophoresis of preterm birth biomarkers, Anal Chem,
2019, 91, 7418–7425.
[121] Kotz, F., Risch, P., Arnold, K., Sevim, S., Puigmartí-Luis, J., Quick, A., et al. Fabrication of
arbitrary three-dimensional suspended hollow microstructures in transparent fused silica
glass, Nat Commun, 2019, 10, 1–7.
[122] Femmer, T., Kuehne, A. J. C., Wessling, M. Print your own membrane: Direct rapid prototyping
of polydimethylsiloxane, Lab Chip, 2014, 14, 2610–2613.
[123] Bhattacharjee, N., Parra‐Cabrera, C., Kim, Y. T., Kuo, A. P., Folch, A. Desktop‐
stereolithography 3D‐printing of a poly(dimethylsiloxane)‐based material with sylgard‐184
properties, Adv Mater, 2018, 30(22), 1800001.
[124] Li, F., Macdonald, N. P., Guijt, R. M., Breadmore, M. C. Increasing the functionalities of 3D
printed microchemical devices by single material, multimaterial, and print-pause-print 3D
printing, Lab Chip, 2019, 19, 35–49.
[125] Rogers, C. I., Qaderi, K., Woolley, A. T., Nordin, G. P. 3D printed microfluidic devices with
integrated valves, Biomicrofluidics, 2015, 9, 016501.
[126] Bhargava, K. C., Thompson, B., Malmstadt, N. Discrete elements for 3D microfluidics, Proc
Natl Acad Sci, 2014, 111, 15013–15018.
[127] Yuen, P. K. SmartBuild–A truly plug-n-play modular microfluidic system, Lab Chip, 2008, 8,
1374–1378.
Xiao Chen, Mengfan Zhang, Tingting Wan, Penghui Fan, Kai Shi,
Yingshan Zhou, Weilin Xu, Pu Xiao
Chapter 5
3D printing of biomaterials

5.1 Introduction
Three-dimensional (3D) printing, as a rapid prototyping technology, can fabricate
customized or complex objects via layer-by-layer printing through computer-aided
design (CAD), without the need for molds [1, 2]. Compared to conventional subtrac-
tive manufacturing technologies, 3D printing is more flexible and efficient, wastes
lesser materials and fabrication of complex elaborate structures can be carried out
more easily [3]. Due to these merits, 3D printing has found wide application in vari-
ous fields ranging from jewelry, robotics and electronic products to food, pharmaceu-
tical and biomedical devices [4, 5]. In the last few decades, 3D printing technology
has developed rapidly and many technologies have emerged. Of these technologies,
photopolymerization-based 3D printing – for example, stereolithography (SLA), digi-
tal light processing (DLP) and continuous liquid interface production (CLIP) as well
as two-photon polymerization (2PP) – are capable of producing complex 3D substruc-
tures with high precision, fast formation and spatial/temporal control [6, 7].
In photopolymerization photocuring 3D printing, printable materials mainly con-
sist of (meth) acrylate- or epoxide-based monomers and oligomers and photoinitia-
tors. Upon exposure to light source, photoinitiators can be converted into the reactive
species, for example, radicals or cations, which then react with monomer and oligo-
mer units to drive the chain growth by radical or cationic mechanism [8]. Therefore, a
liquid system (monomers and oligomers) is rapidly transformed into solids with regu-
lar geometry. Considering their biomedical applications, photoactive biopolymer pre-
cursors are usually used instead of monomers/oligomers in photopolymerization
photocuring 3D printing systems. The typical photopolymerization mechanisms are
thus chain growth, chain step growth and cycloaddition [9].

Xiao Chen, Mengfan Zhang, Tingting Wan, Penghui Fan, Kai Shi, College of Materials Science
and Engineering, Wuhan Textile University, Wuhan, People’s Republic of China
Yingshan Zhou, College of Materials Science and Engineering, Wuhan Textile University, Wuhan,
People’s Republic of China; State Key Laboratory of New Textile Materials and Advanced Processing
Technologies, Wuhan Textile University, Wuhan, People’s Republic of China
Weilin Xu, State Key Laboratory of New Textile Materials and Advanced Processing Technologies,
Wuhan Textile University, Wuhan, People’s Republic of China
Pu Xiao, Research School of Chemistry, Australian National University, Canberra, Australia

https://doi.org/10.1515/9783110570588-005
176 Xiao Chen et al.

In this chapter, an overview of recent progress in the field of photocuring 3D

printing and highlights of novel 3D printable photopolymerizable bio macromolecules
are provided. Also, the emerging representative biomedical applications regarding the
3D printing of biomaterials, including tissue regeneration or repair, drug delivery and
other applications are also discussed. In the end, this chapter also provides current
and future perspective of 3D printing of biomaterials and their limitations.

5.2 Photopolymerizable systems for 3D printable

biomaterials
Using 3D printing techniques via photopolymerization, photopolymerizable systems
can be converted into solid 3D printing objects. These 3D printing techniques via pho-
topolymerization mainly include stereolithography (SLA), digital light processing
(DLP) and continuous liquid interface production (CLIP) [10–12].

5.2.1 Photoinitiators

In photopolymerization-based 3D printing systems, a suitable photoinitiator is a pri-

mary requisite to guarantee an adequate polymerization rate and to avoid toxic effects
of the produced materials for cells and surrounding tissues [13]. In addition, important
characteristics, for example, water solubility, stability and absorption spectrum, should
be considered [14]. A number of available biocompatible photoinitiators are listed
below [1, 15]. As shown in Table 5.1, these are mainly radical photoinitiators (e.g., UV-
light-sensitive or visible-light-sensitive photoinitiators), which are widely used in bio-
medical applications, due to their biocompatibility. Although cationic photoinitiators
are commonly used in photocuring systems, their potential toxicity from protonic acids
produced in the process of photopolymerization limit their use as biomaterials [16].
Up to now, many commercially available cytocompatible UV-light-sensitive pho-
toinitiators have been used in 3D printing applications [17–20]. Irgacure 819 was re-
ported for the photopolymerization of PEGDA in a DLP process [17]. Considering the
fact that a number of bio macromolecules are water-soluble photopolymerizable pre-
cursors, a water-soluble UV-sensitive photoinitiator is required. Water-soluble Irga-
cure 2959, VA-086 and Irgacure 651 have been exploited in biocompatible 3D printing
systems; for example, the fabrication of hydrogel scaffolds for cell culture [18–20].
Another water-soluble photoinitiator, Lithium phenyl (2,4,6-trimethylbenzoyl) phos-
phinate (LAP), can absorb light at longer wavelength than UV to initiate the photo-
polymerization reaction in 3D printed systems [21].
Although 3D printing using UV photopolymerization is available, high-energy
UV light exposure may demonstrate potential deleterious effects on the cells or
 Chapter 5 3D printing of biomaterials 177

Table 5.1: Examples of common photoinitiators used for 3D printing.

Name Abbreviation Category

-hydroxy-ʹ-(-hydroxyethoxy)-- Irgacure  UV-light-sensitive

methylpropiophenone

,-dimethoxy--phenylacetophenone Irgacure , DMPA

Phenyl bis(,,-trimethylbenzoyl) phosphine oxide Irgacure , BAPO

Diphenyl(,,-trimethylbenzoyl) phosphine oxide Darocure TPO

,ʹ-azobis[-methyl-n-(-hydroxyethyl) VA-
propionamide]

Lithium phenyl (,,-trimethylbenzoyl) phosphinate LAP

Camphorquinone CQ Visible-light-
sensitive
Tris(,-bipyridyl) dichlororuthenium (II) hexahydrate Ru

Eosin Y –

Riboflavin –

surrounding tissues [22]. Compared to the UV light, visible light with longer wave-
lengths than UV is friendlier to living cells and is preferable for biomedical applica-
tions and in dentistry [23, 24]. Due to this benefit, several photopolymerizable systems
containing visible-light-sensitive photoinitiators (e.g., camphorquinone, eosin Y and
Ru) have been used in biocompatible 3D printing applications [13]. More details on the
recently developed novel photoinitiating systems for one-photon and two-photon 3D
printing are presented in Chapter 1 and Chapter 2.

5.2.2 Photopolymers

As mentioned earlier, photopolymers precursors are always used to replace small

molecular monomers/oligomers to fabricate biomaterials via photocuring 3D print-
ing techniques. These photopolymers should be biocompatible, and have mechani-
cal and biological features that are fit for human organs or tissues. And they should
be able to be prepared using synthetic or natural polymers. Synthetic polymers pos-
sess good mechanical performance but poor biological properties, while natural poly-
mers provide inherent biological properties and functions that resemble the ECM but
present limited mechanical strength and potential immunogenicity [25]. However,
most of synthetic or natural polymers have no photoreactive moieties in their molecu-
lar chains, and thus, are unable to undergo light-mediated reactions [26]. An avail-
able strategy is the introduction of photoreactive pendant groups (e.g., vinyl group,
methyl acryloyl group, norbornene and tyramine) into the polymer backbone to
178 Xiao Chen et al.

obtain photo-cross-linkable polymer precursors [27–30]. A variety of synthetic and

natural polymers, including poly(ethylene glycol), poly(vinyl alcohol), chitosan, algi-
nate, hyaluronic acid, cellulose, collagen or gelatin and silk fibroin, have been ex-
ploited to prepare these photopolymers precursors.

5.2.2.1 Synthetic polymer-based photopolymerizable precursors

(Meth)acrylated poly(ethylene glycol)

Polyethylene glycol (PEG) is a nontoxic water-soluble polymer, which is approved
by the food and drug administration (FDA). It is widely used in food, cosmetics and
pharmaceuticals. (Meth)acrylated poly(ethylene glycol) (e.g., PEGDA, PEGDMA and
PEGMA) can generally be synthesized by the reaction of PEG with (meth) acryloyl
chloride (Figure 5.1). PEGMA can be used to yield biocompatible 3D structures with
diverse architectures via a 3D printing/ vat photopolymerization [31]. PEGDA can
also be copolymerized with other polymers to prepare tablets with various geometries,
for delivery of poorly soluble drugs using photoinitiated 3D inkjet printing [32]. By
using acrylamide-PEGDA mixture as photopolymerizable precursors, highly stretchable
hydrogels can be prepared via DLP based 3D printing (Figure 5.2) [33]. More interest-
ingly, these hydrogels are capable of forming strong interfacial bonding with commer-
cial 3D printing elastomers, realizing 3D printing of hydrogel-elastomer hybrids, which
significantly simplifies the process of fabricating conductive hydrogel-based flexible
electronics.

Figure 5.1: Synthesis of PEGDA.

Methacrylated polycaprolactone
Polycaprolactone (PCL) is semicrystalline aliphatic polyester synthesized by ring-
opening polymerization of caprolactone. PCL is biocompatible and biodegradable.
It can be degraded by hydrolysis of its ester linkages in physiological conditions
and has, therefore, attracted more attention for use as implantable biomaterials.
Methacrylated polycaprolactone can be synthesized by the reaction between PCL
and methacrylic anhydride (Figure 5.3) [34]. It was often used to fabricate multi-
scale porous scaffolds as bone repair materials via photopolymerization-based 3D
printing.
 Chapter 5 3D printing of biomaterials 179

Load

Unload

Stretch

Unstretch
150 μm

Figure 5.2: Highly stretchable hydrogels from PEGDA for UV curing based 3D printing. Reproduced
with permission from [33]. Copyright 2018 Royal Society of Chemistry.

Figure 5.3: Synthesis of methacrylated polycaprolactone.

Methacrylated poly(vinyl alcohol)

Poly(vinyl alcohol) (PVA) is a water-soluble synthetic polymer produced by the hy-
drolysis of polyvinyl acetate. It has been widely investigated as promising biomaterial
for artificial cartilage, cardiovascular tissue and drug delivery systems because of its
biocompatibility and tissue-like viscoelasticity. Methacrylated PVA can be easily syn-
thesized by using methacrylic anhydride to modify -OH of PVA (Figure 5.4) [35]. It
can be frequently cross-linked with gelatin methacryloyl to fabricate complex cell-
laden constructs by DLP process. To improve mechanical strength and cell adhesion of
PVA-based materials, methacrloyl PVA with ultralow degrees of substitution was syn-
thesized, and subsequent methacrloyl PVA/methacrylate-functionalized silica nano-
composite hydrogels were developed via the photopolymerization approach [36]. This
kind of system is expected to be a photopolymerizable precursor in photopolymeriza-
tion-based 3D printing.
180 Xiao Chen et al.

Figure 5.4: Synthesis of methacrylated PVA.

Poly (propylene fumarate)

Poly (propylene fumarate) (PPF) is an unsaturated linear polyester synthesized from
propylene glycol and fumaric acid, using an acidic catalyst (Figure 5.5). PPF has dou-
ble bonds in the backbone, allowing its cross-link via free radical polymerization
with other photoactive monomers, using a photoinitiator. PPF has tunable degrada-
tion, biocompatibility and osteoconductivity [37]. In particular, PPF-based materials
have well-matched surface properties suitable for regeneration of bone, which makes
them promising candidates for bone tissue engineering [38]. Based on those reasons,
PPF has been used for the fabrication of tissue engineering scaffolds via SLA 3D
printing technique [39].

O O
HO OH p-Toluenesulfonic acid O OH
OH + HO HO O
O O n

Figure 5.5: Synthesis of PPF by a one-step method.

5.2.2.2 Natural polymer based photopolymerizable precursors

Protein-based photopolymerizable precursors

Photoactive gelatin
Gelatin, derived from collagen, is an FDA-approved biopolymer. Its backbone con-
tains Arg-Gly-Asp (RGD) tripeptides that are able to bind cell surface integrins,
making it suitable for promoting cell adhesion and proliferation [40]. Compared
to its precursor collagen, gelatin is less immunogenic and exhibits high water sol-
ubility [41]. Gelatin has been widely used for 3D printing in various biomedical
applications. However, its gelation kinetics is too slow to be efficient for the 3D
printing process [42]. Therefore, photoactive gelatin has been extensively devel-
oped by methacrylation (Figure 5.6). And methacrylated gelatin (GelMA)-based
tissue constructs with mesoscale pore networks have been fabricated via photopo-
lymerization 3D bioprinting (Figure 5.7).
 Chapter 5 3D printing of biomaterials 181

O
NH
O NH
O
NH
O O
O

NH2
NH2 O
NH2 O
OH
EDC NH
/NHS
NH
O NH
O

Figure 5.6: Synthesis of photoactive gelatin.

However, methacrylated gelatin (GelMA) cross-linking is still slow and often in-
hibited by dissolved oxygen (i.e., the well-known oxygen inhibition effect for free
radical polymerization) [43]. Although the oxygen inhibition can be overcome by
improving UV light dosage, this approach is undesirable due to the potential dam-
age to cells [44]. To solve these problems, the UV-initiated thiol-ene click reaction
has emerged as a promising alternative. Compared to conventional chain-growth
polymerization mechanisms, thiol-ene click reaction (step-growth polymerization
mechanism) exhibits faster reaction kinetics, relatively homogenous networks and
improved cell viability [43]. Thiol-norbornene gelatin-based 3D printing objects
(Figure 5.8) via photopolymerization have been created through reaction between
norbornene-modified gelation (GelNB, Figure 5.6) and thiol-containing (macro)mol-
ecules in the presence or absence of a photoinitiator [43]. And these photoclick scaf-
folds can be a benefit for cell viability, cell proliferation and cell difference, which
make them an excellent candidate for use in tissue engineering applications and as
a valuable alternative to replace the GelMA [45].

Methacrylated collagen
Collagen is the most abundant mammalian protein and the main component of con-
nective tissues. It shows excellent biological performance and can promote the adhe-
sion and differentiation of cells as well as the formation of functional tissues, which
make it useful in tissue engineering; for example, skin tissue and vascular tissue scaf-
folds [28]. Similar to a methacrylated gelatin, methacrylated collagen can also be syn-
thesized by the reaction between collagen and methacrylic anhydride. Methacrylated
collagen, together with photoinitiators – for example, I2959 or VA-086 – may be ex-
posed to UV light to cross-link the collagen fibers and create a cell-laden 3D printing
construct. Although these 3D printed constructs have structural rigidity, they are still
mechanically weak and need further cross-linking [47].
182 Xiao Chen et al.

Figure 5.7: Bioprinting of complex constructs with mesoscale pore networks. Reproduced with
permission from [46]. Copyright 2020 Springer Nature.

Methacrylated bovine serum albumin

Bovine serum albumin (BSA) is a water-soluble globular protein with a net negatively
charged surface. The globular shape and negatively charged surface of the protein
confer an extremely high solubility in water (reaching up to ~ 40 % w/v) and low in-
trinsic viscosity (not self-assembling or aggregating), which perfectly meets the de-
signing requirement of new oligomeric and polymeric resins for SLA. Based on that,
methacrylated BSA was firstly used to afford a 3D printed construct via SLA process,
and then the 3D printed construct was thermally cured to afford a denatured protein
construct with improved mechanical properties [48].
 Chapter 5 3D printing of biomaterials 183

Figure 5.8: Z stability in printed constructs fabricated from A) GelNB + LAP, B) GelMA + LAP, C) and
GelNB + I2959, D) and GelMA + I2959. Scale bars are 10 mm. Reproduced with permission from [43].
Copyright 2019 American Chemical Society.

Methacrylated silk fibroin

Silk fibroin (SF), derived from Bombyx mori, has been used for various biomedical
applications, due to its biocompatibility, biodegradability, promotion of cell adher-
ence and proliferation and low inflammation [49]. Similar to gelatin, SF has amine
groups in its molecular chain and can be modified with glycidyl methacrylate to ob-
tain methacrylated SF (Figure 5.9). Methacrylated SF was used to fabricate 3D printed
silk fibroin hydrogels by DLP process [50]. This type of hydrogel enabled cell viability,
proliferation and differentiation to chondrogenesis, and can be expected to be used
for cartilage regeneration.

O
O

O
o HO NH
NH2
NH
NH2
OH

Figure 5.9: Schematic presentation for methacrylation of silk fibroin with glycidyl methacrylate.
184 Xiao Chen et al.

Soy protein isolate

Soy protein isolate (SPI), a plant derived protein, is an attractive material for bio-
medical applications, due to its ease of isolation and processing, tailorable biode-
gradability and low immunogenicity. SPI contains 3.7 mol % tyrosine, which can be
used for photo-cross-linked materials via dityrosine cross-linking [51]. Based on
that, SPI was used to fabricate 3D-printable photo-cross-linked scaffolds or hybrid
scaffolds for tissue engineering applications.

Polysaccharide-based photopolymerizable precursors

(Meth)acrylated chitosan
Chitosan, a natural polysaccharide with a structure similar to glycosaminoglycan in
extracellular matrix of nature tissue, is one of the most promising bio macromole-
cules for biomedical applications, due to its excellent biological properties such as
biodegradability, biocompatibility and promotion of tissue regeneration [52]. (Meth)
acrylated chitosan can be synthesized by the reaction between chitosan and various an-
hydrides or acrylates (Figure 5.10). Photo-cross-linkable N-maleyl chitosan methacrylate

OH

OH OH
O O OH O
O O
O O
HO HO O O
HO HO
NHAc m NH n
NHAc m NH n

O C O C

1.1,2-Epoxybutane
Methacrylic anhydride 2. Methacrylic anhydride

OH OH
O O
O O
HO HO
NHAc m NH2 n

1. Maleic anhydride
HO
2. GMA
O
OH O O
O O
O O
HO HO
NHAc m NH n
H
O C C C COOH
H

Figure 5.10: Synthetic procedures of photoactive chitosan.

 Chapter 5 3D printing of biomaterials 185

(MA-CS-GMA) was prepared and then was used to fabricate 3D grip-shaped MA-CS-
GMA-based scaffolds, via multi-photon polymerization [53]. This 3D hybrid scaffold
could promote matrix mineralization that is suitable for bone tissue engineering. To
mimic the dynamic movement of the tissues, hydroxybutyl methacrylated chitosan
(HBC-MA) was synthesized and further used to fabricate hydrogel scaffolds with a shape
memory property, via SLA process [54]. To increase polymerization rates and overcome
the disadvantage of cell damage from UV exposure, methacrylated chitosan, was mixed
with LAP to be processed into complex 3D hydrogel structures with high resolution,
high-fidelity and good biocompatibility through DLP printing, using blue light [55].

Methacrylated alginate
Alginate, a linear unbranched polysaccharide derived from seaweed that contains
the repeating units of 1,4-linked β-D-mannuronic acid and α-L-guluronic acid, has
been used in drug delivery, cell encapsulation and tissue regeneration, due to its
biocompatibility and biodegradability [56]. Methacrylated alginate (MAA) can be
synthesized by the reaction of alginate with methacrylic anhydride or mechacrylate
(Figure 5.11). Just like GelMA, MAA-based materials lack versatility in mechanical
properties and lasting 3D structures. Therefore, MAA is usually compounded with
other polymers or nanoparticles to fabricate 3D printed scaffold via photopolymeri-
zation. For instance, MAA was used to prepare composite long-lasting scaffolds for
3D bioprinting of highly aligned muscle tissue [57]. In addition, MAA and graphene
oxide were also used to fabricate 3D printed scaffolds for cartilage tissue engineer-
ing [58]. By sacrificing some component in printed hydrogel, complex channels
within cell-laden hydrogels could be fabricated via 3D bioprinting (Figure 5.12) [59].
This approach can potentially provide a platform for fabricating vascularized tissues.

Photoactive hyaluronic acid

Hyaluronic acid (HA), a main component of the extracellular matrix found in vari-
ous tissues of the body, is an attractive candidate for tissue scaffolds because of its
biocompatibility, biodegradability and non-immunogenic property [60]. Photoac-
tive hyaluronic acid can be synthesized by molecular modification of methacrylic
anhydride, norbornene and tyramine. Methacrylated HA was used to prepare cell-
laden hydrogels with complex channels via 3D bioprinting [59]. To produce stable-
shaped 3D printed construct, norbornene-modified HA (Figure 5.13), together with
thiol-containing molecules was used to obtain this kind of construct via photopoly-
merization-based 3D printing [61, 62]. In the same way, a tyramine-modified HA
was synthesized, and it could undergo a dual cross-linking mediated by horserad-
ish peroxidase and hydrogen peroxide followed by a visible light cross-linking to
obtain structurally stable soft hydrogel [63].
186 Xiao Chen et al.

O O
O O
NH NH
O C OH O C O
O HO
O OH O
OH HO O OH
O –OOC O
O
OH
O –OOC
OH O
EDC/NHS NH2
O
–OOC –OOC
OH O HO
O O OH O
OH HO O OH
O –OOC O
O
OH
O –OOC
OH

–OOC –OOC
OH O HO
O O OH O
OH HO O OH
O –OOC O
O
OH
O –OOC
O
O

Figure 5.11: Synthetic procedures of methacrylated alginate.

Photoactive cellulose
Cellulose is the most abundant biopolymer with wide applicability in pharmaceutical
industry. A number of photo-cross-linkable cellulose resins have been synthesized
from cellulose and commercial cellulose ethers; for example, carboxymethyl cellulose
and methyl cellulose. Methacrylated cellulose (Figure 5.14) was prepared and used as
a precursor to produce composite scaffold for 3D bioprinting of highly aligned muscle
tissue [57]. Tyramine-functionalized carboxylmethyl cellulose (Figure 5.15) was also
synthesized and used to fabricate 3D printed in situ tissue sealant with visible-light-
cross-linking [30]. Also, tyramine-modified cellulose was used for other 3D bioprint-
ing applications [64].
 Chapter 5 3D printing of biomaterials 187

Figure 5.12: Digital designs and corresponding 3D devices. All channels were injected with a red
food coloring. Reproduced with permission from [59]. Copyright 2019 Elsevier Ltd.

Other methacrylated polysaccharides

Other methacrylated polysaccharides, for example, pectin and pullulan, were used
to fabricate 3D constructs via multiscale light-assisted 3D printing for cell scaffolds
or dermal tissue engineering [65, 66]. For example, a methacrylated pectin was syn-
thesized by the reaction pectin and methacrylic anhydride, and its bioink was de-
signed to tethering of integrin-binding motifs and preparation of hydrogels via UV
photopolymerization and ionic gelation (Figure 5.16). These printed constructs can
provide a suitable microenvironment for cell behaviors.

5.2.2.3 Extracellular matrix-derived photopolymerizable precursors

Native extracellular matrix (ECM) can provide a structure architecture that contains
adhesion sites for cell surface receptors, facilitating cell attachment, growth and
maturation [29]. The material derived from decellularized tissue-specific ECM can
 188

O O

O OH HO
O OH HO O O
C O O
C O O
O
O
HO O
HO O
OH OH NHCOCH3 n
NHCOCH3 n
Xiao Chen et al.

MAA O
OH

O OH HO OH
C O O
O
HO O
OH NHCOCH3 n

OH
Tyramine

O HO OH
C O O
O
HO O
OH NHCOCH3 n

Figure 5.13: Synthetic procedures of photoactive hyaluronic acid.

 Chapter 5 3D printing of biomaterials 189

Figure 5.14: Synthesis of methacrylated cellulose.

Figure 5.15: Synthesis of tyramine functionalized carboxylmethyl cellulose.

provide these same functions as native ECM [67]. Based on this, a methacrylated kid-
ney ECM-derived bioink was developed and used to form ECM-like hydrogel by 3D
bioprinting via photopolymerization (Figure 5.17) [68]. And it was found that this hy-
drogel could accelerate renal tissue formation. Through the same strategy, methacry-
lated liver ECM-derived bioink was applied to fabricate liver microtissue by DLP
bioprinting [69]. The results showed that hiHep cells could spread farther and show
better hepatocyte-specific functions in this liver microtissue, indicating it would be a
potential liver tissue engineering product that can help restore hepatic functions.

5.3 Applications in biomedical fields

5.3.1 3D printing of biomaterials for bone regeneration

To simulate composition and geometric structure of natural bone, hydroxyapatite and

tricalcium phosphate (HA/TCP), the major constituents of natural bone and teeth, to-
gether with photocurable resins were used to fabricate HA/TCP scaffolds with complex
geometry including biomimetic features and hierarchical porosity via SLA process and
sintering (Figure 5.18) [70]. This 3D printed HA/TCP scaffold with biomimetic hierarchi-
cal structure is biocompatible and has sufficient mechanical strength for surgery, as
investigated by experiments on cell proliferation and surgery in a nude mouse in vivo
 Extrudable, ionically Printable and biofunctional Bioprinted, dual cross-linked
190

cross-linked hydrogel cell-laden bioink cell-laden hydrogel

Photoinitiator
Xiao Chen et al.

5 mm
Calcium chloride hNDFs
UV light

Ionic crosslinking Extrusion Bioprinting Photopolymerization

Pectin chain Methacrylate RGD Thioether bond Methacrylate kinetic chain Chemical cross-link Ionic cross-link

Figure 5.16: Schematic illustration of the design and preparation of the biofunctional bioink for extrusion bioprinting. Reproduced with permission
from [66]. Copyright 2018 Royal Society of Chemistry.
 Acidic
SDS/ solution/ MAA UV
Triton X100 Pepsin

Normal kidney Decellularized kidney Solubilized kidney KdECM methacrylate Cross-linked

ECM (KdECM) (KdECMMA) KdECMMA

Figure 5.17: Schematic illustration of a photo-cross-linkable kidney-specific ECM hydrogel. Reproduced with permission from [68]. Copyright 2019 John
Wiley & Sons.
Chapter 5 3D printing of biomaterials
191
 (a) Natural bone (b)
192

3D printed scaffold

Nature.
10 μm
500 μm
Nanoscale porous structure
Xiao Chen et al.

100 μm
(c) Sintered
Interior of long bone

10 μm Micro-scale holes
100 μm
250 μm
Fracture surface of long bone
Microscale porous structure

(d) HA/TCP Scaffold with hierarchical porous structure

Microscale pores Nanoscale pores

HA/TCP Photo-curable polymer Platform
nanoparticles
Debinding Sintering
HA/TCP slurry
Teflon film
Glass plate
Light Linear stage
DMD Mirror HA/TCP
Green part Brown part
Lens scaffold
Bio-ceramic suspension Multi-scale bio-ceramic printing Post-processing

TCP scaffold; c. Microscope and SEM images of biomimetic HA/TCP scaffolds after sintering; and
d. Fabrication of HA/TCP scaffold. Reproduced with permission from [70]. Copyright 2020 Springer
Figure 5.18: Schematic diagram of 3D printed HA/TCP scaffold with bioinspired hierarchical porous
structure. a. A nude mouse long bone image; b. Microscopy of printed green part of biomimetic HA/
 Chapter 5 3D printing of biomaterials 193

model of long bone. In the future, other biodegradable polymers or growth factors will
be integrated into this scaffold to further accelerate bond healing.

5.3.2 3D printing of biomaterials for soft tissue repair

5.3.2.1 Skin regeneration

3D bioprinted cellularized constructs can instruct entrapped cells to secrete new ECM
components, which are attractive for tissue repair, especially for dermal repair because
of limited self-reparative ability of the dermis upon injury [71]. Pectin-based 3D con-
structs were prepared via 3D printing and ionic cross-linking (shown in Figure 5.16)
[66]. These printed constructs can support the deposition of endogenous ECM, rich in
collagen and fibronectin by entrapped dermal fibroblasts, and are required for the gen-
eration of biomimetic skin constructs.

5.3.2.2 Cartilage regeneration

Cartilage injury is often caused by traumas, diseases and sport accident, and does
not self-heal soon, due to avascularity and a poor supply of repair cells around the
tissue [72]. 3D bioprinting offers an alternative strategy for dealing with cartilage
damage by simultaneously integrating living cells, biomaterials and biological cues
to provide a scaffold. GelMA based cell-laden cartilage tissue constructs with core-
shell nanospheres were prepared via SLA process [73]. This construct showed high
cell viability and proliferation rate, indicating its potential for cartilage repair. To
enhance the printability and cell proliferation further, a photo-cross-linkable algi-
nate/gelatin/chondroitin sulfate composite construct involving the graphene oxide
nanofiller was fabricated via 3D printing [58]. The composite scaffold presented
high cell proliferation and chondrogenic differentiation, favoring cartilage tissue re-
generation. In order to improve mechanical properties of scaffolds to satisfy the
stringent requirement for load-bearing as bioscaffolds, poly (N-acryloyl-2-glycine)/
GelMA (PACG-GelMA) biohybrid scaffold consisting of top layer of PACG-GelMA hy-
drogel-Mn2+ and bottom layer of hydrogel-bioactive glass was fabricated for the re-
pair of osteochondral defects by a 3D printing technique (Figure 5.19) [74]. The
biohybrid hydrogel scaffold can support cell attachment and spreading and en-
hance gene expression of chondrogenic-related/osteogenic-related differentiation
of human bone marrow stem cells, facilitating concurrent regeneration of cartilage
and subchondral bone in a rat model. To prolong the degradation time matching to
cartilage regeneration, gelatin/hyaluronic acid composite construct was fabricated
by integrating photocuring 3D printing and lyophilization techniques [75]. This scaf-
fold combined with chondrocytes can regenerate mature cartilage with typical
 (a)
194

(b)
Bioink A Bioink B 3D printing Scaffold
(The bottom layers) (The top layers)

UV
Xiao Chen et al.

Low-temperature
receiver (–10 °C)
In vivo
(c)

O
H 2N
O N
Osteochondral HO H
NH
regeneration COOH
O HN
HO NH2
Scaffold degradation Scaffold O
ACG
new tissue growth implantation GeIMA

ACG: GeIMA: Mn2+: BG: Triple helixes:

Figure 5.19: Schematic illustration of 3D printing of the biohybrid gradient scaffolds for repair of osteochondral defect. Reproduced with permission
from [74]. Copyright 2019 John Wiley & Sons.
 Chapter 5 3D printing of biomaterials 195

lacunae structure and cartilage-specific extracellular matrixes both in vitro and in

the autologous goat model, making it a potential candidate for use in cartilage re-
generation (Figure 5.20).

A1 B1 C1

A2 B2 C2

100μm 100μm 100μm

A3 B3 C3

100μm 100μm 100μm

HE Safranin O Collagen II

Figure 5.20: Gross view and histological examinations of the regenerated cartilage in and autologous
goat. After 8 weeks of autologous implantation in the goat, 2-week in vitro samples successfully
regenerate relatively homogeneous mature cartilage with typical lacunae structures and cartilage-
specific ECM deposition. Reproduced with permission from [75]. Copyright 2018 American Chemical
Society.

5.3.2.3 Vascularized tissues

3D bioprinting can fabricate hydrogel constructs with embedded microchannels,

which are useful for basic studies on vascularization and angiogenesis, and for the
development of organ-on-a-chip biodevices for disease modeling. By sacrificing some
component in printed hydrogel, complex channels within cell-laden hydrogels could
be fabricated via 3D bioprinting [59]. This hydrogel construct can promote adherence
and confluence of endothelial cells within microchannels (Figure 5.21), favoring the
formation of vascularized tissues.
196 Xiao Chen et al.

(a) (b)

(c)

Figure 5.21: Fluorescent images of the hUVECs cultured within channels. (a) Maximum projection
image from top. Cross-sectional (b) and top (c) view of the channels. Reproduced with permission
from [59]. Copyright 2019 Elsevier Ltd.

5.3.2.4 Neuronal repair

Neurodegenerative diseases always result in irreversible neuronal damage and death.

To treat these diseases, an alternative strategy is to deliver cells to targeted location
and to provide a suitable microenvironment to differentiate these cells into functional
neuronal networks. GelMA-multiferroic nanoparticles composite helical hydrogel mi-
croswimmer was prepared via photocuring 3D printing [76]. While soft GelMA hydrogel
chassis was degraded by enzymes secreted by cells, multiferroic nanoparticles dis-
played magnetoelectric features to transport the bioactive chassis with neuron-like
cells loaded to targeted location. The approach has good potential in targeted cell ther-
apies for traumatic injuries and diseases in the central nervous system.

5.3.2.5 Renal/liver tissue repair

Decellularized tissue-specific ECM can provide the same functions as native ECM.
Based on this, a methacrylated kidney ECM-derived bioink was developed and could
be used to form ECM-like hydrogel by 3D bioprinting via photopolymerization [68]. It
was found that this hydrogel could accelerate renal tissue formation. Through the
same strategy, methacrylated liver ECM-derived bioink was used to fabricate liver mi-
crotissue by DLP bioprinting [69]. This construct could promote the spread of hiHep
 Chapter 5 3D printing of biomaterials 197

cells and have better hepatocyte-specific functions, making it a potential liver tissue
engineering product to help restore hepatic functions.

5.3.3 Drug delivery systems

3D printing has been investigated as a new route to manufacture tables, mainly due
to its precise control over tablet geometry and porosity, which can confer tunable
control over drug dissolution. PEGDA-based tablets were prepared for the delivery
of poorly soluble drugs (carvedilol) using photoinitiated 3D inkjet printing [32].
These tablets can release drug accurately by varying the tablet geometry. Specifi-
cally, the release behavior of carvedilol was fastest for the thin films, followed by
the ring, mesh and cylindrical geometries.

5.4 Conclusions and perspectives

As a model-free manufacturing technology, photopolymerization-based 3D printing
can fabricate various complex and fine constructions in relatively high printing
speed, if a suitable efficient photoinitiator is used. These printed objects have been
studied in various fields such as tissue engineering, biomedical devices and drug
delivery. However, despite its rapid progress, several challenges still exist and limit
its further development. First, more biocompatible photocurable precursors (photo-
sensitive resins) with low viscosity and high performance must be developed to
match the fast and precise printing of 3D biomaterials. Second, the development of
biocompatible photoinitiators with both longer wavelengths absorbance and high
efficiency of initiation is of considerable importance to rapid and accurate forma-
tion of 3D printed biomaterials under mild condition. There is still room for improve-
ment in this field even though significant progresses have been made recently, as
discussed in Chapter 1 and Chapter 2. Third, for 3D printed biomaterials as tissue engi-
neering scaffolds, the realization of sufficient vascularization in material-cell con-
structs to obtain a whole organ with the biological functionality and structure similar
to a native organ, may be a great challenge. All in all, photopolymerization-based 3D
printing opens a new paradigm in tissue engineering and biomedicine fields.

References
[1] Bagheri, A., Jin, J. Photopolymerization in 3D printing, ACS Appl Polym Mater, 2019, 1, 593–611.
[2] Weems, A. C., Perez-Madrigal, M. M., Arno, M. C., Dove, A. P. 3D printing for the clinic:
Examining contemporary polymeric biomaterials and their clinical utility, Bio
macromolecules, 2020, 21, 1037–1059.
198 Xiao Chen et al.

[3] Li, J., Wu, C., Chu, P. K., Gelinsky, M. 3D printing of hydrogels: Rational design strategies and
emerging biomedical applications, Mater Sci Eng R-Rep, 2020, 140, 100543.
[4] You, S., Li, J., Zhu, W., Yu, C., Mei, D., Chen, S. Nanoscale 3D printing of hydrogels for cellular
tissue engineering, J Mat Chem B, 2018, 6, 2187–2197.
[5] Xu, X., Robles-Martinez, P., Madla, C. M., Joubert, F., Goyanes, A., Basit, A. W., Gaisford,
S. Stereolithography (SLA) 3D printing of an antihypertensive polyprintlet: Case study of an
unexpected photopolymer-drug reaction, Addit Manuf, 2020, 33, 101071.
[6] Zhang, J., Xiao, P. 3D printing of photopolymers, Polym Chem, 2018, 9, 1530–1540.
[7] Quan, H., Zhang, T., Xu, H., Luo, S., Nie, J., Zhu, X. Photo-Curing 3D printing technique and its
challenges, Bioact Mater, 2020, 5, 110–115.
[8] Fu, J., Yin, H., Yu, X., Xie, C., Jiang, H., Jin, Y., Sheng, F. Combination of 3D printing
technologies and compressed tablets for preparation of riboflavin floating tablet-in device
(TiD) systems, Int J Pharm, 2018, 549, 370–379.
[9] Pei, M., Mao, J., Xu, W., Zhou, Y., Xiao, P. Photocrosslinkable chitosan hydrogels and their
biomedical applications, J Polym Sci Pol Chem, 2019, 57, 1862–1871.
[10] Rossi, S., Puglisi, A., Benaglia, M. Additive manufacturing technologies: 3D printing in
organic synthesis, ChemCatChem, 2018, 10, 1512–1525.
[11] Layani, M., Wang, X., Magdassi, S. Novel Materials for 3D printing by photopolymerization,
Adv Mater, 2018, 30, 1706344.
[12] Tumbleston, J. R., Shirvanyants, D., Ermoshkin, N., Janusziewicz, R., Johnson, A. R., Kelly, D.,
Chen, K., Pinschmidt, R., Rolland, J. P., Ermoshkin, A., Samulski, E. T., Desimone,
J. M. Continuous liquid interface of 3D objects, Science, 2015, 347, 1349–1352.
[13] Guerra, A. J., Lara-Padilla, H., Becker, M. L., Rodriguez, C. A., Dean, D. Photopolymerizable
resins for 3D-printing solid-cured tissue engineered implants, Curr Drug Targets, 2019, 20,
823–838.
[14] Shih, H., Lin, C. C. Visible-light-mediated thiol-ene hydrogelation using eosin-Y as the only
photoinitiator, Macromol Rapid Commun, 2013, 34, 269–273.
[15] Lin, H., Zhang, D., Alexander, P. G., Yang, G., Tan, J., Cheng, A. W. M., Tuan, R. S. Application
of visible light-based projection stereolithography for live cell-scaffold fabrication with
designed architecture, Biomaterials, 2013, 34, 331–339.
[16] Nguyen, K. T., West, J. L. Photopolymerizable hydrogels for tissue engineering applications,
Biomaterials, 2002, 23, 4307–4314.
[17] Chiappone, A., Fantino, E., Roppolo, I., Lorusso, M., Manfredi, D., Fino, P., Pirri, C. F.,
Calignano, F. 3D printed PEG-based hybrid nanocomposites obtained by sol-gel technique,
ACS Appl Mater Interfaces, 2016, 8, 5627–5633.
[18] Chan, V., Zorlutuna, P., Jeong, J. H., Kong, H., Bashir, R. Three-dimensional photopatterning
of hydrogels using stereolithography for long-term cell encapsulation, Lab Chip, 2010, 10,
2062–2070.
[19] Occhetta, P., Visone, R., Russo, L., Cipolla, L., Moretti, M., Rasponi, M. VA-086 Methacrylate
gelatine photopolymerizable hydrogels: A parametric study for highly biocompatible 3D cell
embedding, J Biomed Mater Res Part A, 2015, 103, 2109–2117.
[20] Warner, J., Soman, P., Zhu, W., Tom, M., Chen, S. Design and 3D printing of hydrogel
scaffolds with fractal geometries, ACS Biomater Sci Eng, 2016, 2, 1763–1770.
[21] Palaganas, N. B., Mangadlao, J. D., De Leon, A. C. C., Palaganas, J. O., Pangilinan, K. D., Lee,
Y. J., Advincula, R. C. 3D printing of photocurable cellulose nanocrystal composite for
fabrication of complex architectures via stereolithography, ACS Appl Mater Interfaces, 2017,
9, 34314–34324.
[22] Hu, J., Hou, Y., Park, H., Choi, B., Hou, S., Chung, A., Lee, M. Visible light crosslinkable
chitosan hydrogels for tissue engineering, Acta Biomater, 2012, 8, 1730–1738.
 Chapter 5 3D printing of biomaterials 199

[23] Zhang, J., Dumur, F., Xiao, P., Graff, B., Bardelang, D., Gigmes, D., Fouassier, J. P., Lalevee,
J. Structure design of naphthalimide derivatives: Toward versatile photoinitiators for near-UV/
visible LEDs, 3D printing, and water-soluble photoinitiating systems, Macromolecules, 2015,
48, 2054–2063.
[24] Bagheri, A., Arandiyan, H., Boyer, C., Lim, M. Lanthanide-doped upconversion nanoparticles:
Emerging intelligent light-activated drug delivery systems, Adv Sci, 2016, 3, 1500437.
[25] Annabi, N., Tamayol, A., Uquillas, J. A., Akbari, M., Bertassoni, L. E., Cha, C.,
Khademhosseini, A. 25th anniversary article: Rational design and applications of hydrogels
in regenerative medicine, Adv Sci, 2014, 26, 85–124.
[26] Fertier, L., Koleilat, H., Stemmelen, M., Giani, O., Joly-Duhamel, C., Lapinte, V., Robin, J. J.
The use of renewable feedstock in UV-curable materials-A new age for polymers and green
chemistry, Prog Polym Sci, 2013, 38, 932–962.
[27] Xiang, H., Wang, X., Ou, Z., Lin, G., Yin, J., Liu, Z., Zhang, L., Liu, X. UV-curable, 3D printable
and biocompatible silicone elastomers, Prog Org Coat, 2019, 137, 105372.
[28] Gao, Q., Niu, X., Shao, L., Zhou, L., Lin, Z., Sun, A., Fu, J., Chen, Z., Hu, J., Liu, Y., He, Y. 3D
printing of complex GelMA-based scaffolds with nanoclay, Biofabrication, 2019, 11, 035006.
[29] Dobos, A., Hoorick, J. V., Steiger, W., Gruber, P., Markovic, M., Andriotis, O. G., Rohatschek, A.,
Dubruel, P., Thurner, P. J., Vlierberghe, S. V., Baudis, S., Ovsianikov, A. Thiol-gelatin-norbornene
bioink for laser-based high-definition bioprinting, Adv Healthc Mater, 2019, 9, 1900752.
[30] Al-Abboodi, A., Zhang, S., Al-Saady, M., Ong, J. W., Chan, P. P. Y., Fu, J. Printing in situ tissue
sealant with visible-light-crosslinked porous hydrogel, Biomed Mater, 2019, 14, 045010.
[31] Aduba, D. C. Jr, Margaretta, E. D., Marnot, A. E. C., Heifferon, K. V., Surbey, W. R., Chartrain,
N. A., Whittington, A. R., Long, T. E., Williams, C. B. Vat photopolymerization 3D printing of
acid-cleavable PEG-methacrylate networks for biomaterial applications, Mater Today
Commun, 2019, 19, 204–211.
[32] Clark, E. A., Alexander, M. R., Irvine, D. J., Roberts, C. J., Wallace, M. J., Yoo, J., Wildman,
R. D. Making tablets for delivery of poorly soluble drugs using photoinitiated 3D inkjet
printing, Int J Pharm, 2020, 578, 118805.
[33] Zhang, B., Li, S., Hingorani, H., Serjouei, A., Larush, L., Pawar, A. A., Goh, W. H., Sakhaei,
A. H., Hashimoto, M., Kowsari, K., Magdassi, S., Ge, Q. Highly stretchable hydrogels for UV
curing based high-resolution multimaterial 3D printing, J Mat Chem B, 2018, 6, 3246–3253.
[34] Dikici, B. A., Reilly, G. C., Claeyssens, F. Boosting the osteogenic and angiogenic
performance of multiscale porous polycaprolactone scaffolds by in vitro generated
extracellular matrix decoration, ACS Appl Mater Interfaces, 2020, 12, 12510–12524.
[35] Lim, K. S., Levato, R., Costa, P. F., Castilho, M. D., Alcala-Orozco, C. R., Dorenmalen, K. M. A. V.,
Melchels, F. P. W., Gawlitta, D., Hooper, G. J., Malda, J., Woodfield, T. B. F. Bio-resin for high
resolution lithography-based biofabrication of complex cell-laden constructs, Biofabrication,
2018, 10, 034101.
[36] Zhang, C., Liang, K., Zhou, D., Yang, H., Liu, X., Yin, X., Xu, W., Zhou, Y., Xiao, P. High-
performance photopolymerized poly (vinyl alcohol)/silica nanocomposite hydrogels with
enhanced cell adhesion, ACS Appl Mater Interfaces, 2018, 10, 27692–27700.
[37] Gresser, J. D., Hsu, S. H., Nagaoka, H., Lyons, C. M., Nieratko, D. P., Wise, D. L., Barabino,
G. A., Trantolo, D. J. Analysis of a vinyl pyrrolidone/poly (propylene fumarate) resorbable
bone cement, J Biomed Mater Res, 1995, 29, 1241–1247.
[38] Cai, Z., Wan, Y., Becher, M. L., Long, Y. Z., Dean, D. Poly (propylene fumarate)-based
materials: Synthesis, functionalization, properties, device fabrication and biomedical
applications, Biomaterials, 2019, 208, 45–71.
200 Xiao Chen et al.

[39] Guerra, A. J., Lammel-Lindemann, J., Katko, A., Kleinfehn, A., Rodriguez, C. A., Catalani, L. H.,
Becker, M. L., Ciurana, J., Dean, D. Optimization of photocrosslinkable resin components and
3D printing process parameters, Acta Biomater, 2019, 97, 154–161.
[40] Tytgat, L., Damme, L. V., Arevalo, M. D. P. O., Declercq, H., Thienpont, H., Otteveare, H.,
Blondeel, P., Dubruel, P., Vlierberghe, S. V. Extrusion-based 3D printing of photo-
crossllinkable gelatin and k-carrageenan hydrogel blends for adipose tissue regeneration, Int
J Biol Macromol, 2019, 140, 929–938.
[41] Gasperini, L., Mano, J. F., Reis, R. L. Natural polymers for the microencapsulation of cells, J R
Soc Interface, 2014, 11, 2014087.
[42] Boza, A. M., Biegun, M. K. W., Campo, A. D., Lasa, B. V., Roman, J. S. Glycerylphytate as an
ionic crosslinker for 3D printing of multi-layered scaffolds with improved shape fidelity and
biological features, Biomater Sci, 2020, 8, 506–516.
[43] Tigner, T. J., Rajput, S., Gaharwar, A. K., Alge, D. L. Comparison of photocrosslinkable gelatin
derivatives and initiators for three-dimensional extrusion bioprinting, Biomacromolecules,
2020, 21, 454–463.
[44] Svobodova, A. R., Galandakova, A., Sianska, J., Dolezal, D., Lichnovska, R., Ulrichova, J.,
Vostalova, J. DNA damage after acute exposure of mice skin to physiological doses of UVB
and UVA light, Arch Dermatol Res, 2012, 304, 407–412.
[45] Tytgat, L., Damme, L. V., Hoorick, J. V., Declercq, H., Thienpont, H., Ottevaere, H., Blondeel,
P., Dubruel, P., Vlierberghe, S. V. Additive manufacturing of photo-crosslinked gelatin
scaffolds for adipose tissue engineering, Acta Biomater, 2019, 94, 340–350.
[46] Shao, L., Gao, Q., Xie, C., Fu, J., Xiang, M., Liu, Z., Xiang, L., He, Y. Sacrificial microgel-
laden bioink-enabled 3D bioprinting of mesoscale pore networks, Bio-Des Manuf, 2020,
3, 30–39.
[47] Kajave, N. S., Schmitt, T., Nguyen, T. U., Kishore, V. Dual crosslinking strategy to generate
mechanically visible cell-laden printable constructs using methacrylated collagen bioinks,
Mat Sci Eng C, 2020, 107, 110290.
[48] Smith, P. T., Narupai, B., Tsui, J. H., Millik, T. S. C., Shafranek, R. T., Kim, D. H., Nelson,
A. Additive manufacturing of bovine serum albumin-based hydrogels and bioplastics,
Biomacromolecules, 2020, 21, 484–492.
[49] Park, H. J., Lee, O. J., Lee, M. C., Moon, B. M., Ju, H. W., Min Lee, J., Kim, J., Kim, D. W., Park,
C. H. Fabrication of 3D porous silk scaffolds by particulate (salt/sucrose) leaching for bone
tissue reconstruction, Int J Biol Macromol, 2015, 78, 215–223.
[50] Hong, H., Seo, Y. B., Kim, D. Y., Lee, J. S., Lee, Y. J., Lee, H., Ajiteru, O., Sultan, M. T., Lee,
O. J., Kim, S. H., Park, C. H. Digital light processing 3D printed silk fibroin hydrogel for
cartilage tissue engineering, Biomaterials, 2020, 232, 119679.
[51] Dorishetty, P., Balu, R., Sreekumar, A., Campo, L. D., Mata, J. P., Choudhury, N. R., Dutta,
N. K. Robust and tunable hybrid hydrogels from photo-cross-linked soy protein isolate and
regenerated silk fibroin, ACS Sustain Chem Eng, 2019, 7, 9257–9271.
[52] Zhou, Y., Zhao, S., Zhang, C., Liang, K., Li, J., Yang, H., Gu, S., Bai, Z., Ye, D., Xu,
W. Photopolymerized maleilated chitosan/thiol-terminated poly (vinyl alcohol) hydrogels as
potential tissue engineering scaffolds, Carbohydr Polym, 2018, 184, 383–389.
[53] Parkatzidis, K., Chatzinikolaidou, M., Kaliva, M., Bakopoulou, A., Farsari, M.,
Vamvakaki, M. Multiphoton 3D printing of biopolymer-based hydrogels, ACS Biomater Sci
Eng, 2019, 5, 6161–6170.
[54] Seo, J. W., Shin, S. R., Park, Y. J., Bae, H. Hydrogel production platform with dynamic
movement using photo-crosslinkable /temperature reversible chitosan polymer and
stereolithography 4D printing technology, Tissue Eng Regen Med, 2020, 17, 423–431.
 Chapter 5 3D printing of biomaterials 201

[55] Shen, Y., Tang, H., Huang, X., Hang, R., Zhang, X., Wang, Y., Yao, X. DLP printing
photocurable chitosan to build bio-constructs for tissue engineering, Carbohydr Polym,
2020, 235, 115970.
[56] Jeon, O., Bouhadir, K. H., Mansour, J. M., Alsberg, E. Photocrosslinked alginate hydrogels with
tunable biodegradation rates and mechanical properties, Biomaterials, 2009, 30, 2724–2734.
[57] Garcia-Lizarribar, A., Fernandez-Garibay, X., Velasco-Mallorqui, F., Castano, A. G., Ramon-
Azcon, S. J. Composite biomaterials as long-lasting scaffolds for 3D bioprinting of highly
aligned muscle tissue, Macromol Biosci, 2018, 18, 1800167.
[58] Olate-Moya, F. A., Arens, L., Wilhelm, M., Mateos-Timoneda, M. A., Engel, E., Palza,
H. Chondroinductive alginate-based hydrogels having graphene oxide for 3D printed
scaffolds fabrication, ACS Appl Mater Interfaces, 2020, 12, 4343–4357.
[59] Ji, S., Almeida, E., Guvendiren, M. 3D bioprinting of complex channels within cell-laden
hydrogels, Acta Biomater, 2019, 95, 214–224.
[60] Zhang, C., Dong, Q., Liang, K., Zhou, D., Yang, H., Liu, X., Xu, W., Zhou, Y., Xiao,
P. Photopolymerizable thiol-acrylate maleiated hyaluronic acid/thiol-terminated poly
(ethylene glycol) hydrogels as potential in-situ formable scaffolds, Int J Biol Macromol, 2018,
119, 270–277.
[61] Highley, C. B., Song, K. H., Daly, A. C., Burdick, J. A. Jammed microgel inks for 3D printing
applications, Adv Sci, 2019, 6, 1801076.
[62] Galarraga, J. H., Kwon, M., Burdick, J. A. 3D bioprinting via an in situ crosslinking technique
towards engineering cartilage tissue, Sci Rep, 2019, 9, 19987.
[63] Petta, D., Armiento, A. R., Grijpma, D., Alini, M., Eglin, D., D’Este, M. 3D bioprinting of a
hyaluronan bioink through enzymatic- and visible light-crosslinking, Biofabrication, 2018, 10,
044104.
[64] Shin, J. Y., Yeo, Y. H., Jeong, J. E., Park, S. A., Park, W. H. Dual-crosslinked methylcellulose
hydrogels for 3D bioprinting applications, Carbohydr Polym, 2020, 238, 116192.
[65] Giustina, G. D., Gandin, A., Brigo, L., Panciera, T., Giulitti, S., Sgarbossa, P., D’Alessandro,
D., Trombi, L., Danti, S., Brusatin, G. Polysaccharide hydrogels for multiscale 3D printing of
pullulan scaffolds, Mater Des, 2019, 165, 107566.
[66] Pereira, R. F., Sousa, A., Barrias, C. C., Bartolo, P. J., Granja, P. L. A single-component
hydrogel bioink for bioprinting of bioengineered 3D constructs for dermal tissue engineering,
Mater Horiz, 2018, 5, 1100–1111.
[67] Annabi, N., Tamayol, A., Uquillas, J. A., Akbari, M., Bertassoni, L. E., Cha, C., Camci‐Unal, G.,
Dokmeci, M. R., Peppas, N. A., Khademhosseini, A. 25th anniversary article: Rational design
and applications of hydrogels in regenerative medicine, Adv Mater, 2014, 26, 85–124.
[68] Ali, M., Kumar, P. R. A., Yoo, J. J., Zahran, F., Atala, A., Lee, S. J. A photo-crosslinkable kidney
ECM-derived bioink accelerates renal tissue formation, Adv Healthc Mater, 2019, 8, 1800992.
[69] Mao, Q., Wang, Y., Li, Y., Juengpanich, S., Li, W., Chen, M., Yin, J., Fu, J., Cai, X. Fabrication of
liver microtissue with liver decellularized extracellular matrix (dECM) bioink by digital light
processing (DLP) bioprinting, Mat Sci Eng C, 2020, 109, 110625.
[70] Li, X., Yuan, Y., Liu, L., Leung, Y. S., Chen, Y., Guo, Y., Chai, Y., Chen, Y. 3D printing of
hydroxyapatite/ tricalcium phosphate scaffold with hierarchical porous structure for bone
regeneration, Bio-Des Manuf, 2020, 3, 15–29.
[71] Pereira, R. F., Sousa, A., Barrias, C. C., Bayat, A., Granja, P. L., Bartolo, P. J. Advances in
bioprinted cell-laden hydrogels for skin tissue engineering, Biomanuf Rev, 2017, 2, 1.
[72] Zhou, Y., Liang, K., Zhao, S., Zhang, C., Li, J., Yang, H., Liu, X., Yin, X., Chen, D., Xu, W., Xiao,
P. Photopolymerized maleilated chitosan/methacrylated silk fibroin micro/nanocomposite
hydrogels as potential scaffolds for cartilage tissue engineering, Int J Biol Macromol, 2018,
108, 383–390.
202 Xiao Chen et al.

[73] Zhu, W., Cui, H., Boualam, B., Masood, F., Flynn, E., Rao, R. D., Zhang, Z. Y., Zhang, L. G. 3D
bioprinting mesenchymal stem cell-laden construct with core-shell nanospheres for cartilage
tissue engineering, Nanotechnology, 2018, 29, 185101.
[74] Gao, F., Xu, Z., Liang, Q., Li, H., Peng, L., Wu, M., Zhao, X., Cui, X., Ruan, C., Liu,
W. Osteochondral regeneration with 3D-printed biodegradable high-strength supramolecular
polymer reinforce-gelatin hydrogel scaffolds, Adv Sci, 2019, 6, 1900867.
[75] Xia, H., Zhao, D., Zhu, H., Hua, Y., Xiao, K., Xu, Y., Liu, Y., Chen, W., Liu, Y., Zhang, W., Liu, W.,
Tang, S., Cao, Y., Wang, X., Chen, H. H., Zhou, G. Lyophilized scaffolds fabricated from 3D-
printed photocurable natural hydrogel for cartilage regeneration, ACS Appl Mater Interfaces,
2018, 10, 31704–31715.
[76] Dong, M., Wang, X., Chen, X., Mushtaq, F., Deng, S., Zhu, C., Terzopoulou, T. H., Qin, X., Xiao,
X., Luis, J. P., Choi, H., Pego, A. P., Shen, Q., Nelson, B. J., Pane, S. 3D-printed soft
magnetoelectric microswimmers for delivery and differentiation of neuron-like cells, Adv
Funct Mater, 2020, 30, 1910323.
Xiaoqun Zhu, Guoqiang Lu, Jun Nie
Chapter 6
Photopolymerization and its application
in 3D printing of customized objects
6.1 Overview of 3D printing
In contrast to traditional subtractive manufacturing, 3D printing is a kind of addi-
tive manufacturing with rapid prototyping. Subtractive manufacturing involves
processes that reduce materials, like cutting and polishing during jade bracelet
making. In contrast, objects are fabricated through a process of layer-by-layer de-
positing of materials for additive manufacturing. Any complex three-dimensional
structure can be cut into numerous two-dimensional planes along one direction.
This creation of two-dimensional planes supports 3D printing fundamentally. Dig-
ital software can help construct the model data of all these two-dimensional
planes and transmit it to the printer. Then, a three-dimensional object is printed
layer-by-layer under data command. 3D printing is an interesting crossover of ma-
chinery, computer technique and material science; none is dispensable. It is
model-less, designable, customizable and intelligent, greatly reducing the pro-
duction cycle cost while improving the performance of products. 3D printing truly
strikes at the core of the traditional manufacturing industry. 3D printing has
emerged more than 40 years [1] and many technologies, such as selective laser
melting (SLM), selective laser sintering (SLS), fused deposition modelling (FDM)
and stereolithography (SLA), were developed [2–5]. Materials, such as metal, inor-
ganic powder, plastic, liquid photosensitive resin and even paper, can be used in
3D printing [6, 7]. Now, 3D printing technology is applied widely in aerospace, auto-
mobile, medical treatment, jewelry, movie making and other industries. It has pene-
trated into our daily life and brings about great changes to our life constantly.

6.2 Development of photocuring 3D printing

Photocuring 3D printing is the earliest one among 3D printing technologies [8, 9].
The first 3D printer was fabricated based on the principle of photopolymerization.
In the 1970s, four scientists from America and Japan came up with the concept of

Xiaoqun Zhu, Guoqiang Lu, Jun Nie, College of Materials Engineering and Science, Beijing Univer-
sity of Chemical Technology, Beijing, P. R. China

https://doi.org/10.1515/9783110570588-006
204 Xiaoqun Zhu, Guoqiang Lu, Jun Nie

3D printing almost at the same time. However, only Chuck Hull turned the concept
into a reality and founded the first 3D printing company – 3D Systems Corp Com-
pany in 1986 [10]. In the next year, the first 3D printer named SLA-1 was developed
based on stereolithographic appearance (SLA). Due to these outstanding contribu-
tions, Chuck Hull was inducted into the American inventor Hall of Fame in 2014.
Over the last 30 years, many new technologies evolved from photocuring 3D
printing [11–13], such as digital light processing (DLP), [14, 15] liquid crystal dis-
play (LCD), [16, 17] Multi-jet printing (MJP), [18, 19] two-photo 3D printing (TPP),
[20] continuous liquid interface production (CLIP) [21] and so on. The following
sections will introduce some mainstream and cutting-edge photocuring 3D printing
technologies.

6.3 Basic knowledge of photopolymerization

Photocuring 3D printing, based on the principle of photopolymerization, has advan-
tages and disadvantages similar to photopolymerization [6, 9, 22–26]. In this section, a
basic knowledge of photopolymerization related to photocuring 3D printing will be
introduced.
Firstly, the raw materials used in photopolymerization are liquid photosensitive
resins. These resins consist of monomers, oligomers and initiators [9, 27–30]. Ac-
cording to the different polymerization mechanisms, they can be divided into free
radical and cationic photopolymerization. The materials used in free radical photo-
polymerization can be acrylates and vinyl ethers [28, 31, 32]. The materials used in
cationic photopolymerization contain vinyl ethers and epoxies [33, 34].
Monomers, also called active diluents, have low viscosity and just like solvents
can dilute oligomers and dissolve initiators. But different from solvents, their struc-
tures contain active functional groups such as the double-bonds of acrylate and
vinyl ether, the epoxy groups of epoxy resins and oxetane, which can be used for
the reaction of photopolymerization. The monomers may contain one, two or more
reactive functional groups.
Oligomers, usually having high viscosity, are a class of polymers with low molecu-
lar weight, which can determine the final properties of the printed objects [31, 35, 36].
The oligomers mainly include epoxy acrylates, urethane acrylates, polyester acrylates,
polyether acrylates, epoxy resins and others [34, 37].
Photoinitiators are chemicals that are sensitive to light. They produce active
species when exposed to suitable light [38–42]. These active species include free
radicals, cations and anions, which further initiate the polymerization of monomers
and oligomers [43].
In general, the liquid photosensitive resins are very stable without irradiation.
They can be preserved stably for half a year to one year or even longer. But, once
 Chapter 6 Photopolymerization and its application in 3D printing 205

these systems are exposed to suitable light, they will cure rapidly and form a cross-
linked polymer network. For photopolymerization and photocuring 3D printing, the
wavelength of the light source can deterimine the reaction mechanism and the in-
tensity can affect the reaction speed and printing efficiency, which finally affect the
performance of the printed objects.
Photopolymerization has some advantages. Firstly, the reaction can be easily
controlled by switching light on or off. What’s more, light can be controlled spatio-
temporally, endowing possibility to print objects with complex structures. More im-
portantly, the light can be controlled precisely by corresponding equipment, which
will endow the printed objects with high definition. This is one of the reasons why
photocuring 3D printing has the highest molding precision among all the 3D print-
ing technologies.
Secondly, photopolymerization involves a process that changes the system
from liquid to solid. This means that the printed objects are easily separated from
the raw materials, thus allowing a high utilization of raw materials. If equipped
with a high-precision 3D printer, it can even achieve the smooth surface like injec-
tion moldings. But, such a liquid-solid phase transition also has disadvantages for
photocuring 3D printing. For example, it is a common method to add supports for
printing the suspended structures from liquid resins and so it is inevitable to re-
move these supports after printing, which is time-consuming and affect the preci-
sion of objects. They can even cause damage to the printed objects while removing
these supports.
Thirdly, the speed of photopolymerization is pretty fast, only taking a few sec-
onds or even less than one second, that’s why the rapid speed of photocuring 3D
printing. So far, photocuring 3D printing has the fastest printing speed among all
types of 3D printing technologies.
Every coin has two sides and photopolymerization is also no exception. The ad-
vantages of photopolymerization results in photocuring 3D printing and bring
many advantages along with it. Meanwhile, there are also some shortcomings in
photocuring 3D printing that are difficult to overcome.
First of all, free radicals are very sensitive to oxygen and can be quenched by
oxygen, which affect the surface curing especially. Usually, photocured objects pres-
ent a state where the internal structures are solidified completely, but the surface of
the objects remains an uncured liquid state or viscous state. However sometimes,
oxygen inhibition is an advantage in 3D printing. For example, it can solve the problem
of adhesion between layers during printing.
Secondly, volume shrinkage is another drawback which is difficult to overcome
in photopolymerization, which means the volume of the whole system will contract
after polymerization. Before polymerization, the distance between the liquid mole-
cules is the van der Waals distance, which is generally 3.54Å. Nevertheless, it will
be converted to the length of the covalent bond (carbon-carbon single bonds) after
polymerization, 1.54Å, which is nearly 2Å less. The higher the double bonds ratio,
206 Xiaoqun Zhu, Guoqiang Lu, Jun Nie

the higher is the conversion rate and greater is the volume shrinkage. Usually, the
volume shrinkage of epoxy systems is relatively smaller than free radical systems,
which is due to the ring tension. After polymerization, the ring structures open and
become straight chains, which can partially replenish the loss of the van der Waals
distance. This is the reason why the volume shrinkage of cationic polymerization is
relatively small.
What’s more, volume shrinkage will cause great internal stress in objects. Due
to the rapid photopolymerization, the rate of volume shrinkage can’t match well
with the rate of polymerization. Hence, the volume shrinkage will be not synchro-
nized during polymerization, which induced the internal stress of the printed ob-
jects. To lessen the internal stress, polymer chains will move after polymerization,
which would lead to deformation and instability of the printed objects, conse-
quently the printed object is broken. This is the main reason why photocured ob-
jects easily warp while using.
In addition, liquid photosensitive resins used for photocuring 3D printing al-
ways contain a lot of small molecules, which will result in a low crosslinking den-
sity after photopolymerization, obviously affecting the performances of printed
objects. Therefore, printed objects usually have poor mechanical properties such
as hardness, brittleness, insufficient toughness and so on. These drawbacks se-
verely limit the application areas and are the main reason why it is difficult to im-
prove the market share of photocuring 3D printing. At present, photocuring 3D
printing technology is mainly used in fields that require only transitional and tem-
porary features.

6.4 Advantages and disadvantages of photocuring

3D printing
It is easy to summarize the advantages and disadvantages of photocuring 3D print-
ing by combing the characteristics of photopolymerization with 3D printing. The ad-
vantages of photocuring 3D printing include:
(1) Fast molding speed
(2) High precision
(3) Good surface quality (Smooth surface)
(4) Customizable objects with complex and fine structure
(5) High utilization of raw materials

At the same time, photocuring 3D printing also has disadvantages:

(1) Limited strength, stiffness, heat resistance and usually brittleness
(2) Easy deformation of the printed objects
(3) High cost of production and maintenance
 Chapter 6 Photopolymerization and its application in 3D printing 207

(4) Require post-curing

(5) Require supports for some objects with suspended structures that can easily
damage printed objects while removing the supports

6.5 Types of photocuring 3D printing

To understand and master photocuring 3D printing technologies quickly, it can pro-
ceed from the following key points. The first is the wavelength of the light source
which determines the polymerization mechanism and the kind of initiators be used.
Because the initiators can’t be excited by a lamp with mismatched wavelength, the
reaction can’t be initiated consequently. Secondly, it is necessary to know the inten-
sity of the light source, as it affects the speed of photopolymerization and further
influences the printing efficiency. The stronger the intensity of the light source, the
faster is the speed of photopolymerization and higher is the conversion rate of poly-
merization. Specifically, cationic photopolymerization is sensitive to light intensity
and cationic initiators are difficult to be initiated under low light intensity. The
third is the exposure method, it can be divided into point and surface exposure or
up and down exposure. By understanding the above information, researchers can
simply judge the printing precision and speed of the machine. In this section, some
mainstream photocuring 3D printing will be briefly introduced.

6.5.1 Stereo lithography apparatus (SLA)

Stereo lithography apparatus (SLA) is the earliest and most mature 3D printing tech-
nology among all the available technologies. It is widely used in the industry [11, 12].
There is a lifting platform in a resin tank and lasers can move and scan above the
material tank during printing (Figure 6.1). The process can be explained in more de-
tail as follows. Firstly, the lifting platform rises to the height of a layer-thickness
above the liquid surface. Next, the scraper wipes the liquid level and the laser beam
scans the liquid level point-by-point to initiate polymerization. Then, the lifting plat-
form descends a distance of one layer after one layer of resin is cured. Finally, a three-
dimensional object is printed by repeating the above processes.
Usually, the wavelength of the lamp used in the SLA machine is 355 nm, which
has a strong light intensity. Because it is equipped with a point light source, the
pattern formation is controlled by the path of the laser beam. Theoretically, the
beam can move over an infinite range, so the SLA can print objects of large size.
But the indensity of laser beam will gradually decay with time, which may result in
different extent of polymerization, consequently affect the stability of the printed
objects. It is therefore necessary to repair or change the light source regularly.
208 Xiaoqun Zhu, Guoqiang Lu, Jun Nie

Laser beams

Scraper

Lifting
Cured platform
parts
Supporting
platform Resin tank
Liquid
photosensitive
resins

Figure 6.1: The schematic diagram of SLA.

What’s more, the printing speed is relatively slow due to point exposure. More im-
portantly, the printing precision depends on the size of the laser spots. Thus, the
SLA has low precision when compared with other technologies. Generally, the poly-
merization mechanism of SLA can be free radical or cationic due to the short wave-
length and the strong intensity of the light source. Therefore, it has a broad choice
of initiators [44]. But, pure cationic polymerization is rarely selected due to the less
number of choices of resins and the high price of cation initiators. Hence, hybrid
photopolymerization (radical and cation polymerization) is generally adopted.
Therefore, the volume shrinkage of printed objects is relatively low.
To date, SLA is the unique choice for printing large-sized objects, thus having
broad application in fields such as electronics, medical devices, automotives, aero-
space and so on.

6.5.2 Digital light processing (DLP)

The principle of DLP is shown in Figure 6.2. Here, a projector (digital microscope
device), which consists of a light source and an image control system that are inte-
grated in an exposure module, is used to project the cross-section images of objects
into liquid photosensitive resin [15]. Commonly, it adopts a down-exposure and the
projection system is placed under the resin tank. The bottom of the resin tank is
transparent. There is a release membrane on the side that is in contact with the liq-
uid resin, which helps the cured parts separate from the bottom of resin tank. The
working process is as follows. First, the print platform descends to a layer-thickness
from the bottom of the tank. Then, the projection system casts a light pattern for
curing one-layer liquid resin. Next, the platform goes up to the original position.
 Chapter 6 Photopolymerization and its application in 3D printing 209

Lifting
platform

Resin tank
Cured
Liquid
parts
photosensitive
resins

Digital
microscope
device

Figure 6.2: The schematic diagram of DLP.

Finally, the machine repeats the above processes after the liquid resins replenish
the cured areas until the whole process is finished.
The core part of DLP is its projection system, also called optical semiconductor,
and digital microscope device or DLP chip. This method was invented by Dr. Larry
Hornback in 1977 and commercialized by Texas instruments in 1996. Currently, no
technology can compete with it, which result in a high price of the machine. Usu-
ally, the projection system works with a high precision and adopts surface expo-
sure. That is to say, a whole two-dimensional plane can be solidified through one
projection and only a few seconds are needed to print one layer. Hence, DLP has a
high printing speed and precision. The light source of DLP is LED lamp, which is a
stable light source and has a long service-life. But, these components of the DLP
machine are not tolerant to ultraviolet light. Thus, DLP usually adopts light source
with a wavelength of 405 nm. To maintain high printing precision, the size of the
printed objects is small, generally between 100 mm × 60 mm and 190 mm ×
120 mm. So, it has to sacrifice some precision to print a large-sized object by DLP.
With the evolution of DLP, many advanced DLP technologies with large molding
have appeared in the market.
Due to the weak intensity of the light source, DLP can only adopt the mecha-
nism of free radical photopolymerization and there is need to choose some long-
wavelength initiators such as Irgacure 819, TPO, TPO-L and so on.
DLP can print objects with small size and high precision. Thus, it is more suit-
able in the fields such as jewelry casting, dentistry and so on [15].

6.5.3 Liquid crystal display (LCD)

LCD, basically having the same printing process as the DLP, is a rapidly develop-
ing 3D printing technology in recent years. And the main difference with DLP is
210 Xiaoqun Zhu, Guoqiang Lu, Jun Nie

the light source and imaging system [17]. The principle of LCD printing technology
is shown in Figure 6.3. Its light source is an array of LED beads that are integrated
on a flat plate. For LCD 3D printing technology, the liquid crystal display is used
as the imaging system. When an electric field is applied to the liquid crystal dis-
play, it changes its molecular arrangement and prevents light from passing
through. Consequently, it forms alternate intervals of light and shade, thus realizing
the pattern control of light.

Figure 6.3: The schematic diagram of LCD.

The machine structure is very simple. The LCD screen is a mass-product and
pretty cheap, so the the LCD printer is not expensive. Moreover, the LCD screen
of 8.9-inch, 2 K pixel is widely used at present. This allows a good control for
printing precision. LCD has high molding precision and the printed objects also
have a smooth surface. According to the characteristics of the machine, the size
of the printed objects is slightly larger than those objects printed by DLP. But, the
liquid crystal is not tolerant to ultraviolet rays. Thus, 405nm-LED lamp is adopted.
Moreover, the liquid crystal screen is composed of multiple layers of film, which
strongly block light transmission, so the transmittance is relatively low and usually
less than 10%. Further, it has low polymerization efficiency due to the weak light in-
tensity. Therefore, LCD printing technology can only choose the mechanism of free
radical polymerization. The LCD screen has a limited service life and needs to be re-
paired or replaced regularly. What’s more, there exists a backlight, which allows a
small amount of light to pass through unexposed areas. If the printer is operated for
a long time, the unexposed areas are cured, so it is necessary to clean the resin tank
regularly. Finally, As the light intensity between the lamp beads is nonuniform, the
equipment requires to be treated for uniform light.
At present, it is widely used in dentistry, manual toys, jewelry and so on.
 Chapter 6 Photopolymerization and its application in 3D printing 211

6.5.4 Multi-jet printing/PolyJet (MJP)

MJP, was developed by 3D systems company in 1996. While it was called PolyJet by
Object company from Israeli and later the technology was incorporated into Stra-
tasys company in 2012. The principle of MJP is shown in Figure 6.4. The printed pat-
tern is controlled by nozzle array and a light source is used for curing the liquid
resin. Usually, the number of nozzles can reach hundreds or thousands, so the
molding area is, theoretically, not limited. The principle of MJP is as follows. Photo-
sensitive resins are sprayed on a working platform and cured by a UV lamp. At the
same time, some fusible or soluble materials are used as supporting structures dur-
ing printing. Printing is carried out by a set of special nozzles. After finishing these
processes, the molding platform accurately descends a layer thickness and repeats
the above processes until the whole part is printed. Importantly, MJP can provide
the highest Z-axis resolution, about 16 microns. What’s more, since this technology
has a separate light source system, the wavelength and intensity of the light can be
selected, theoretically, according to resin formulas.

Figure 6.4: The schematic diagram of MJP.

As different nozzles can print different materials, MJP is the only technology that
can print objects with multiple kinds of materials and multiple colors, among all of
the currently available photocuring printing technologies. What’s more, objects
with high precision can be also printed by MJP technology. More importantly, the
supporting materials are soluble or fusible. This is equivalent to embedding the
printed parts in supporting materials. Thus, some soft objects can be printed by
MJP. Finally, the surface of these printed objects is pretty smooth as there are no
sharp supporting-points to other printed parts. However, the threshold of the nozzle
technology is very high, so the equipment is pretty expensive.
MJP can be mainly used in fields requiring high precision such as mold casting,
medical health field, color printing and so on.
212 Xiaoqun Zhu, Guoqiang Lu, Jun Nie

6.5.5 Two-photon 3D printing

Two-photon initiators are the key factors for two-photon 3D printing technology
[20, 45]. Common photoinitiators need to absorb only one photon to produce an ac-
tive center and initiate polymerization. However, two-photon initiators need to ab-
sorb two photons to generate free radicals, so the reaction can take place only at
the focus of two light rays. Thus, the printing precision can reach nano-level. But
the molding speed is very slow, so it is generally used in the area of micro-nano
devices and the machine is expensive.

6.5.6 Continuous liquid interface production (CLIP)

Although many technologies based on photocuring 3D printing have emerged, no

one reflects the advantages of rapid curing of photopolymerization The time for
photocuring can be in milliseconds, but the activities of rising and falling of the
platform take more than 10 s, which greatly weakens the advantages of photocuring.
Until 2015, the continuous and fast printing technology was developed by Carbon
company which broken through the technical bottleneck of traditional photocuring
3D. The technology was reported as a cover article in Science. The printing speed
could reach up to 480 mm/h. This technique was called Continuous Liquid Interface
Production technology (CLIP) [21].
Briefly, CLIP is an advanced technology based on DLP. The principle of CLIP is
shown in Figure 6.5. The key technique is the oxygen-permeable membrane, which
is helpful for continuous printing due to oxygen permeation that inhibits radical
polymerization. The oxygen-permeable membrane lies at the bottom of resin tank.
It permits oxygen to pass through so that these resins that are close to the bottom
of resin tank can’t be cured, allowing stable liquid states to be maintained during
printing. In this way, the liquid resin quickly fills into the groove. Therefore, the
platform needn’t repeat the lifting and falling processes, ensuring continuous print-
ing and greatly increasing the printing speed.
There are two necessary conditions to achieve a high printing speed in CLIP.
One is to print hollow structures. Such structures ensure that the curing area of
each layer is small and that the surrounding liquid resins can replenish to these
printed areas quickly. But, for solid parts, it takes some time for the liquid resins to
flow from around to the middle, which greatly slows down the printing speed.
The second condition is that the photosensitive resin should have low viscosity.
The liquid resins requires to have good liquidity, ensuring that they can flow to the
printed areas quickly. Therefore, the printing speed will be slow for printing solid
objects or using liquid resins with high viscosity.
Now, the most successful application of CLIP is printing of shoe soles or shoe
molds. To obtain good mechanical properties such as good elasticity, stretchability,
 Chapter 6 Photopolymerization and its application in 3D printing 213

Lifting platform

Liquid
photosensitive Cured parts
resins
Dead zone

O2
Permeable
window

Imaging
system Mirror

Figure 6.5: The schematic diagram of CLIP.

high wear resistance and so on, it is necessary to adopt a double-curing mode such
as light-heat curing. The shoe soles or shoe molds are first printed by the photocur-
ing 3D printing technology and then the printed objects are placed in an oven for
secondary curing.
The photocuring 3D printing technologies described so far are relatively mature
and have been widely used in the industry. Recently, new photocuring 3D printing
technologies have also emerged. In 2019, research teams at UC Berkeley and Kelly
of Lawrence Livermore National Laboratory published a report on Volumetric 3D
printing technology (specifically, Volumetric additive manufacturing via tomographic
reconstruction) in Science, which was regarded as a technology that overturned
the traditional photocuring 3D printing technology [46]. Volumetric 3D printing
technology breaks the traditional 3D printing technology where objects are printed
layer-by-layer. The working principle of volumetric 3D printing technology is just like
the reverse computed tomography (CT) scan in which X-ray tubes rotate around pa-
tients to take pictures of the body’s internal organs. These projections are then
used to reconstruct a 3D image by computer. Next, the researchers calculate the
shape of the object from several different angles using a computer. Subsequently,
the resulting 2D images are input into a slide projector and cast into a cylindrical
container containing photosensitive liquid resins. The container then rotates at a
certain angle with the rotation of projector. Any position that can receive light can
be controlled independently and the liquid resin solidifies when the total amount of
light exceeds a certain value. In general, the key point of volumetric 3D printing tech-
nology is CAL algorithm, which is relatively complex and has a high threshold due to
the large computation, which requires the support of high-performance computers.
Of course, there are also many problems during printing such as oxygen inhibition,
214 Xiaoqun Zhu, Guoqiang Lu, Jun Nie

light field interference, conversion and matching between 3D spaces and 2D pro-
jections and so on.
The advantage of volumetric 3D printing technology is its high printing speed –
it can print a small model in dozens of seconds – and high tolerance for the viscos-
ity of photosensitive resins. As we all know, greater the molecular weight greater is
the viscosity of the resin and better is the performance of the printed objects. There-
fore, volumetric 3D printing technology can almost print any structure. But, this
technology requires transparent resins and only can print objects with small-size.
Moreover, the key algorithm is relatively complex.
In 2019, Martin P. de Beer and Harry L. van der Laan, from Michigan University
published an article titled “Rapid, continuous additive manufacturing by volumet-
ric polymerization inhibition patterning” in Science Advance. The printing speed
can reach two meters per hour [47]. Its operating principle is also to keep the bot-
tom of resin tank in liquid state during printing, thereby ensuring that the printing
platform can pull up continuously. But, the method, different from CLIP, achieved
the bottom inhibition by designing the resin formulas. There are two kinds of pho-
tosensitizers in the formulas; one is the visible photoinitiator camphorquinone
(CQ), whose maximum absorption wavelength can reach more than 500 nm (The
458 nm-wavelength LED lamp is adopted during printing). The other photosen-
sitizer is the free radical inhibitor bis[2-(o-chlorophenyl)-4,5-diphenylimidazole]
(o-CI-HABI), which can produce free radical inhibitors to capture free radicals and
prevent them from initiating polymerization. Here, the absorption wavelength of in-
hibitors is less than 450nm, which can be initiated by the 365 nm-wavelength LED
lamp. Two rays of different wavelengths irradiate the same position at the same
time during printing. Rays that have a long wavelength exhibit stronger penetrability
than rays that have short wavelength, so free radicals and inhibitors can generate
simultaneously at the bottom of resin tank. Here, the free radicals are suppressed
and thus can’t initiate polymerization. The resins at the bottom of the tank are main-
tained in liquid state during printing. Because the rays of short wavelength can’t pen-
etrate the upper layer, they only produce free radicals to initiate polymerization. In
this way, the resins at the bottom of the tank are always kept in liquid state, guaran-
teeing continuous photocuring 3D printing.

6.6 Materials of photocuring 3D printing

Photosensitive resins are the main materials for photocuring 3D printing and directly
determine the performances of printed objects [6, 9, 26–28, 37, 48, 49]. Therefore, it is
necessary for photosensitive resins to meet these following requirements:
(1) Good matching of the machine’s light source and light intensity – Different print-
ers have different light sources; their wavelengths and light intensities differ. The
 Chapter 6 Photopolymerization and its application in 3D printing 215

wavelength determines the type of initiators and the photocuring mechanism,

while the light intensity affects the usage of initiators or the rate of photocuring.
(2) Low viscosity – Whether the process is layer-by-layer pull-down or continuous
pull-up, the resins should have good leveling and should be tiled at the bottom of
the material tank or tiled on the surface of cured objects within a short time during
printing (especially in the process of continuous pull-up). All these processes re-
quire resins with low viscosity and the requirements of viscosity vary greatly for
different printing technologies. Generally, the main purpose of adding reactive dil-
uent is to adjust and reduce the viscosity of the photosensitive resin formulas.
(3) Small volume shrinkage – Volume shrinkage, caused by the transformation of
Van der Waals distance between the liquid molecules into covalent bond after
photocuring, is an inherent and inevitable phenomenon in photopolymerization.
What’s more, there are still some unreacted double-bonds that are enclosed in
printed objects after finishing, which may undergo slow polymerization. And
generally, there is a need for post-curing treatment of photocuring objects. These
phenomena also result in volume shrinkage, to a certain extent. More impor-
tantly, it is difficult to ensure uniform light for three-dimensional objects at the
same time. This results in a nonuniform conversion rate of double-bonds, further
generating uneven stress relaxation. Generally, the wall thickness of the objects
is uneven due to the asymmetry of the three-dimensional objects in space. As a
result, the stress relaxation generated in each direction is inhomogeneous. These
stresses are difficult to neutralize, finally causing some problems such as defor-
mation, cracking, crimp and imprecise size for printed objects.
(4) A highly primary curing degree – The primary curing refers to the curing that
occurs during printing. To some extent, the volume shrinking during printing
can be reduced by supplementing with surrounding liquid resins. Therefore,
post-curing is seldom required if the double-bonds conversion is high during
primary curing, resulting in a shrinking of a small volume or a low degree of
deformation.
(5) High strength under wet state – It refers to the strength of the printed objects at
primary-molding, which will guarantee less deformation, expansion and inter-
laminar peeling during the post-curing process. The material strength of the
primary-molding includes a variety of mechanical properties such as stress,
strain, modulus, hardness and adhesion between layer and layer. Only the high
strength of primary-molding can ensure that the printed parts will not deform
and the layers will not separate from each other when they are pulled out or
scraped during printing.
(6) Small swelling degree – When all or some of the printed parts are immersed in
the liquid photosensitive resin during printing, the size of the printed objects
will be inaccurate if swelling occurs. Specifically, if the polarity of the mono-
mers matches well with the polymer or if the polymer has a low cross-linking
density, the monomer with small molecules may enter the polymer networks
216 Xiaoqun Zhu, Guoqiang Lu, Jun Nie

when these cured parts are immersed in the liquid resins. Therefore, it is neces-
sary to design an appropriate resin formula and cross-linking density of the
polymer to ensure low swelling.
(7) Stable storage, no reaction and no sedimentation at room temperature – The
resins need to have stable performances without irradiation, which will be ben-
eficial for transportation and storage.
(8) Good photosensitivity and high curing speed – The resins are sensitive to UV
light and cured quickly under low light intensity.
(9) Low odor, low irritation and low toxicity – It is necessary to consider the odor
and toxicity of monomers and oligomers when designing the formulas.

Apart from above requirements, there are also several points required to be consid-
ered. The systems used for photocuring 3D printing can be divided into free radical,
cationic and hybrid photopolymerization according to the mechanisms.
Free radical photopolymerization is a reaction where free radicals induce the poly-
merization of double-bonds [25]. It has many advantages, such as a wide variety of
monomers, resins and initiators for choosing, high technical maturity, rapid curing
speed and so on, so have broad application in traditional UV industry. The commonly-
used free radical monomers are acrylate, vinyl and vinyl ether, whose degree of func-
tionality can be 1, 2, 3 or multi-functionality. These monomers usually have low viscos-
ity and can be used to dilute resins and dissolve initiators.
Resins, which can be used for free radical photopolymerization, include ure-
thane acrylates, epoxy acrylates, polyester acrylates and polyether acrylates [29–32,
35, 50]. Generally speaking, urethane acrylates have good flexibility and wear resis-
tance, but there are many intermolecular or intramolecular hydrogen bonds due to
the presence of a large number of amine-ester bonds, hence they have high viscosity.
Epoxy resins have high polymerization speed and high strength, but high brittleness
and are easily prone to yellowing. Polyester acrylates have good curing quality and
the resin properties can be adjusted over a wide range. Polyether acrylates have good
flexibility and good anti-yellowing properties owing to the existence of a large num-
ber of ether bonds in their molecular chain, but the materials made printed by poly-
ether acrylates are relatively soft and have poor mechanical strength and chemical
resistance.
Free radical photoinitiators can be divided into cracking-type and hydrogen-
grabbing type [38–44]. Cracking-type initiators are generally used in photocuring 3D
printing owing to their high initiation speed. It should choose the photoinitiators of
matched absorption wavelength with that of the light source of the printer. For exam-
ple, we can choose initiators that have high efficiency and low cost such as Irgacure
1173, 184, for the light source with 355 nm-wavelength. While the initiators, such as
Irgacure TPO and 819, can be selected when the machine is equipped with the light
source of 385 nm, 395 nm or 405 nm-wavelengths. If there is a visible light in the
printer, the photoinitiators can be Irgacure 784, camphor quinone (CQ), etc. But they
 Chapter 6 Photopolymerization and its application in 3D printing 217

are high cost and colored, especially Irgacure 784 which is red, thus limiting the appli-
cation in light or colorless resins.
In summary, free radical photosensitive resins have good photosensitivity, fast
curing speed and low cost. They are the earliest materials used in photocuring 3D
printing. However, there is a large volume shrinkage in the printed molds and
parts, which easily deformed while using.
Cationic photopolymerization is a reaction that proton-acid induces the polymer-
ization of epoxy, oxetane and vinyl ether [25, 33, 34, 37]. The ring-opening polymeri-
zation has low volume shrinkage, no oxygen inhibition. But, the induction period of
cationic photopolymerization is relatively long and these reactions are at low speed.
Therefore, these systems have relatively few applications in traditional photopolyme-
rization. More importantly, they offer a less choices of monomers, resins and initia-
tors, so the cost is higher than those of free radical systems. At present, pure cationic
photopolymerization system is seldom used in photocuring 3D printing.
The monomers that can be used for cationic photopolymerization include epoxy,
oxetane and vinyl ether, and the most commonly used monomers are epoxies. The
cationic initiators include sulfonium salt, iodonium salt and sensitizing agent [39,
43]. However, the current technology of cationic photopolymerization with long
wavelength is not mature, so the mechanism of cationic photopolymerization can’t
be used in photocuring 3D printing except SLA. Therefore, it has great significance in
photocuring 3D printing fields to research the cationic photopolymerization with
long wavelength, low-intensity of light and fast reaction speed.
By combining the advantages of free-radical and cationic photonitiators, hybrid
photopolymerization will be a better choice for photocuring 3D printing. At present,
hybrid photosensitive systems are used mainly in SLA (355 nm) [51]. The printed ob-
jects and parts have characteristics such as low volume shrinkage and high precision.
Due to the numerous advantages of photopolymerization, it can be used in
many fields. However, the traditional UV materials are developed mainly for surface
coating materials, just for protection and decoration and not for bulk materials.
Photocuring 3D printed objects are bulk materials, requiring materials with good
physical and mechanical properties, heat resistance, biocompatibility, casting and
degradable properties. In order to expand the application field and market share of
photocuring 3D printing, it is very important to research new photocurable materi-
als with properties similar to engineering plastics [11, 23, 26, 48, 52, 53].
The group of Zhou Feng synthesized a kind of polyimide acrylate resins by com-
bining the structure of polyimide with the functional group of acrylates, which are
used for photocuring 3D printing to print objects with high temperature resistance
(as shown in Figure 6.6) [53]. The printed objects can be used for a long time at
300 °C by blending these resins with active diluents (as shown in Figure 6.7),
whose glass transition temperature is 242 °C and the tensile properties of the
printed materials at 300 °C are slightly lower than those at room temperature.
 218

6FOHA

6FDA
MA
SiDA

Polyamic acid (PAA)

Xiaoqun Zhu, Guoqiang Lu, Jun Nie

Polyimide (PI)

Polyimide grafted GMA (PI-g-GMA)

Figure 6.6: The process of synthesizing polyimide acrylate resin. Reproduced with permission from [53]. Copyright 2017, Royal Society of Chemistry.
 Chapter 6 Photopolymerization and its application in 3D printing 219

30

25
Tensile strength (MPa)

20

15

10

0
25°C 300°C

4,000 0.30
Storage modulus
242 °C Tan δ
3,500
0.25
Storage modulus (MPa)

3,000
0.20
2,500

2,000 0.15
Tan δ

1,500
0.10
1,000

500 0.05
73 MPa
0 0.00
0 50 100 150 200 250 300 350 400 450
Temperature (°C)

Figure 6.7: Tensile properties (left) and dynamic mechanical properties (right) of polyimide
photosensitive resins at different temperatures. Reproduced with permission from [53]. Copyright
2017, Royal Society of Chemistry.

6.7 Application of photocuring 3D printing

With the collaborative development of hardware, software and materials, photocur-
ing 3D printing has developed rapidly in recent years and its application fields are
also continuously expanding [54, 55]. At present, the application fields of photocur-
ing 3D printing have these following characteristics: personalization, small batch,
complex structures, high precision and so on. It is mainly used in dental medicine
[56], jewelry, earphone hearing aid, glasses, shoes manufacturing, education and
220 Xiaoqun Zhu, Guoqiang Lu, Jun Nie

so on [57–60]. Some optical images of printed objects by photocuring 3D printing

are shown in Figure 6.8.

Figure 6.8: Optical images of the printed objects by photocuring 3D printing.

6.7.1 Application of photocuring 3D printing in dentistry

Dentistry is the most typical and successful application of photocuring 3D printing

[5]. Dental orthodontics and dental implant are the most widely used projects as well
as having high added value. The emergence of 3D printing has overturned the tradi-
tional dental medical technology, which make dental orthodontics and implants
more precise, efficient and comfortable.
Nowadays, people have more demands on the quality of life and pay more atten-
tion to their personal image. Having a nice smile and even teeth can provides people
with more confidence. So, dental medicine has a huge market all over the world. Ac-
cording to the survey, the dental market in China is growing rapidly, with an annual
growth rate of about 15% in the recent years. Therefore, as an emerging and advanced
technology, 3D printing technology has a broad application in the field of dentistry.

6.7.1.1 Application of photocuring 3D printing in dental orthodontics

Orthodontics correct the deformity in teeth by using the principle of biomechanics.

Mechanical forces are applied to the teeth by means of attaching various orthodon-
tic devices and used to align teeth.
 Chapter 6 Photopolymerization and its application in 3D printing 221

Metal braces correction, known as “steel teeth”, is one of the most commonly
used methods to correct teeth deformity. Specifically, this method uses steel wires
to fix the teeth firstly. The doctor then adjust the teeth to desired position based on
their own experience and skill. We can clearly see metal braces and steel wires on
the surface of teeth which gives others a feeling of “iron tooth and bronze tooth”.
More importantly, the metal braces and steel wires are easy to cause friction with
the mouth. This brings foreign body sensation and stimulates oral mucosa. Further,
food residues are easy to be remained on the metal braces and steel wires, growing
bacteria and causing oral inflammation.
Invisible orthodontics, also called “Invisalign appliance”, are widely favored
by people who want to have beautiful teeth. There are no steel wires and metal
braces in the process of correction. More importantly, traditional technology of in-
visible orthodontics is time-consuming, costly and the precision is reduced after
several times of turning-model.
Digital invisible orthodontic use the mechanism of force application and ab-
sorption by biomechanics. First, suitable force is applied on the teeth. Then, the
force is transmitted to the alveolar bone of the stressed side due to the hardness of
the teeth (teeth do not undergo any significant change). Next, the alveolar bone
will slowly absorb the force and realign the teeth. At the same time, the other side
of alveolar bone will slowly reconstruct and regenerate owing to the drag force.
Here, the most important process is the biological force applied to the teeth. It must
be accurately calculated to balance the reconstruction tension with the absorption
pressure of the alveolar bone. If the doctor can operate well, they will safely com-
plete the objective of aligning the teeth and adjusting the occlusal relationship of
the upper and lower jaws. By using digital invisible orthodontics, doctors can ob-
tain the patient’s oral data using a oral scanner, which is used for constructing 3D
models. After diagnosis and personalized design, the doctors can accurately calcu-
late the biological force of each pair of braces by using digital software and can de-
duce the model evolution. The model data is then transmitted to printer. Finally,
doctors turn these molds into transparent braces so that the patients can wear them
in sequence. This method not only saves time and causes less damage to teeth, it
also enables patients wearing the braces comfortably, looking beautiful and clean-
ing their mouth easily and maintaining oral health.
According to the statistics of Henry Schein, there are 2.06 million cases of or-
thodontics in China and the market size was 24.72 billion yuan in 2017, with an an-
nual growth rate of about 15%. It can be forecasted that there is a huge potential for
dental orthodontics in the future and photocuring 3D printing will develop rapidly
in the field of dental orthodontics.
222 Xiaoqun Zhu, Guoqiang Lu, Jun Nie

6.7.1.2 Application of photocuring 3D printing in dental prostheses

The same as traditional invisible orthodontics, traditional dental prostheses also

involve a series of complicated processes such as biting mold, turning mold, im-
planting and so on. Such a complex process will be precision-damaging and time-
consuming. Dental prostheses usually require a high precision and are of small
size, which are in accordance with the technical characteristics of photocuring 3D
printing. With the development of 3D printing technology, digital dental prostheses
have been realized through a series of precise operations such as scanning the pa-
tient’s oral, converting them into model data and then transmitting to photocuring
3D printer. These processes replace the plaster model and ensures accuracy while
repairing.

6.7.1.3 Application of photocuring 3D printing in dental surgery guide plate

Dental guide plate planting technology has evolved recently. Simply speaking,
guide plate is just like navigation while driving a car. The structures of the teeth are
so complex that only gums can be seen from the surface. Doctors can’t see the loca-
tion of the alveolar bones and neural tube during traditional dental implant. They
may complete the entire process of dental plant by flap surgery, incision or other
operations. Such a process can result in a large wound and need long time for pa-
tients to recover. With the help of digital technology, doctors can get the location of
alveolar bone and neural tube through cone beam computer tomography (CBCT)
and design the implant guide plate by software before the operation. In this way,
doctors can ensure the success of the surgery and post-repair by controlling the po-
sition, direction and size of the implant. In short, digital guide plant can greatly
improve the accuracy of surgery, especially for some complex implant surgery that
may damage important anatomical structures.

6.7.2 Application of photocuring 3D printing in jewelry

manufacturing

For a long time, jewelry manufacturing relied on hand-sketched and hand-

carved wax molds, which is time-consuming and inefficient. 3D printing technol-
ogy can greatly shorten the production time of jewelry prototypes by combining
CAM (computer-aided manufacturing) and CAD (computer-aided design). In com-
parison to traditional hand-drawing, designers can create new and unique de-
signs more easily using CAD, which can also help those people who are not
good at painting to transform their ideas into reality, so everyone can easily
make and modify a piece of jewelry. What’s more, it is very convenient to design
 Chapter 6 Photopolymerization and its application in 3D printing 223

models using CAD and designers needn’t worry about the problem of dimension
accuracy because CAD programs will automatically adjust the model size. No
matter how complex the model is, it only takes a few hours to finish the model
design completely. In addition, these designs can be stored in a computer per-
manently and it is also easy to get a part of the model and copy it into other
models. By using shadow and reflection to let the preview more realistic during
designing, designers and customers can also clearly see the appearance of jew-
elry from the designs. The model designed by CAD can be converted into three-
dimensional data and the output quickly obtained from a 3D printer. Owing to
the high precision of photocuring 3D printing, it can make more complex and
fine structures than hand-carving. More importantly, many models can be printed
together, which greatly saves time and improves efficiency and accuracy. Finally,
the printed models can be turned into various kinds of metal jewelry by casting.
The photosensitive resins used for printing jewelry are required to have excel-
lent characteristics such as low volume shrinkage, high dimensional accuracy,
small thermal expansion, no residue after burning and no corrosion to plaster
molds.
Due to its difference from the traditional wax models, the casting parameters
and the process of photocuring 3D printing should be readjusted. It is therefore nec-
essary for foundry and researchers to explore suitable casting processes. But the
casting process is relatively complex and confidential among foundries, so the tech-
nique level is uneven, which is one of the main factors for 3D printing being diffi-
cult to popularize in the field of jewelry.

6.7.3 Application of photocuring 3D printing in earphones

and hearing-aids
Customized earphones and hearing-aids can match well with the owner’s auricle,
which will insulate users from outside noise and achieve the optimal hearing. Spe-
cially, the auricle model can be obtained by scanner, then these 3D data of auricle
model will be transmitted to printer, finally the earphones or hearing-aids will be
printed by photocuring 3D printer.
Because the earphones and hearing-aids are directly contacted with human
skin for a long time, the materials of earphones must be biocompatible. At the same
time, it is necessary to have high precision, transparence and good resistance to
yellowing for the printed earphones.
According to the statistical data of the world health organization, 15% of adults
have hearing loss all over the world. The total market of hearing-aids was 4.7 billion
dollars in 2015, and will reach 7 billion dollars by 2024, with an average annual
growth rate of 4.5%.
224 Xiaoqun Zhu, Guoqiang Lu, Jun Nie

6.7.4 Application of photocuring 3D printing in customized

glasses
Nowadays, more and more people wear glasses to correct vision and spectacles
manufacturing has developed into a large-scale industry. Commonly, spectacle
frames are basically the same due to standardized and large-scaled manufacturing.
However, there are no two identical faces in the world and the space between the
pupils is exactly not the same. Therefore, there is an urgent need in the market for
precise and customized glasses.
The breakthrough in 3D printing has brought a solution for customized glasses.
Optometrists can design the structure of glasses on demand so as to enhance the
comfort of the owner and create a personalized style. Specially, the facial profile of
a customer can be obtained using a scanner and the most comfortable position of
the spectacle lens can be determined by analyzing the facial data. Then, the frame,
whose color and other details can be adjusted easily, can be customized according
to the unique facial features. What’s more, customers can observe the wearing ef-
fect by an online design system.

6.7.5 Application of photocuring 3D printing in shoe

manufacturing
Apart from dentistry, shoe manufacturing is also likely to be a new large-scale and
high value-added area for photocuring 3D printing. In 2017, the market of China’s
shoe industry reached 400 billion yuan.
Each person has feet that are special in size and shape. The size may be the
same but the shape may be totally different. Traditional shoe manufacturing often
uses one mold for the same size, which can’t meet personalized needs. However,
photocuring 3D printing coupled with software design can easily meet these de-
mands. According to the characteristics of consumers, personalized shoes can be
designed, which can not only effectively reduce the weight of the shoes but also
provide excellent shock absorption so as to achieve the best wearing experience.
In 2015, the development of CLIP laid the foundation for rapid 3D printing.
Later, Adidas and Carbon printed the middle soles of shoes by CLIP. They produced
5,000 pairs of shoes in 2018 and the price was 333 dollars per pair. They produced
100,000 pairs in 2019 and they planed to produce 5 million pairs in 2020. More
importantly, Carbon company layed out comprehensive patent to protect the tech-
nology and corresponding materials. If other companies want to make shoes by
photocuring 3D printing, they must break through these pioneering effort and es-
tablish their own proprietary mechanism. Else, when there is a conflict of intellec-
tual property, it will bring huge trouble to their company.
 Chapter 6 Photopolymerization and its application in 3D printing 225

Because the shoes need to bear the weight of the whole person, the perfor-
mance requirements of the materials are very high –good elongation at break, tear
strength, rebound resilience, wear-resistance and so on.
In addition to these applications, photocuring 3D printing also has been appli-
cated in garage kits, model design, culture products and so on.

6.8 Problems in photocuring 3D printing

Although photocuring 3D printing came into being more than 30 years, it still com-
mands a low market share compared to metal 3D printing and plastic 3D printing.
The main reason is the low performance of the printed objects due to aspects such
as high brittleness, insufficient toughness and so on. Thus, it is necessary to im-
prove performances and there are two points that need to be considered. One is to
design and synthesize new resins suitable for photocuring 3D printing, which can
combine the structural unit of engineering plastics with photosensitive structures
so as to improve the mechanical and thermal performance of printed objects [11, 26,
48, 61–63]. The second is software design which can indirectly improve properties
by designing corresponding three-dimensional spatial structures [52]. At present,
the existing problems include:
(1) Lack of photosensitive resin with high performance (low viscosity, low volume
shrinkage)
(2) Large volume shrinkage of free radical photopolymerization and low reactivity
of cationic photopolymerization
(3) Incompatibility between high quantity of fillers and fast printing for composite
systems
(4) Low storage stability of double-component (photo-thermal) systems
(5) Treatment of solid waste after using the models
(6) Printing only small-sized objects using DLP and LCD
(7) Long curing time and low conversion rate in LCD
(8) Low printing precision in SLA
(9) Problem between high-speed printing and poor surface quality or precision
(10) Printers with high printing speed only for hollow structures
(11) Requirement of supporting structures and post-processing is time-consuming
and manpower-wasting
(12) Difficulty in printing soft objects and using resins with high viscosity
(13) Absence of high-level education combined with 3D printing
(14) Absence of competitiveness and independent innovation
(15) Require to increase the online market for 3D printing
226 Xiaoqun Zhu, Guoqiang Lu, Jun Nie

6.9 Conclusions and perspectives

Although there are many problems, we still can believe that photocuring 3D printing
has a promising prospect. First of all, photocuring 3D printers had the fastest growth
rate in the global layout of 3D printers from 2018 to 2020. The amount of materials also
grew rapidly in the same period – it increased by 25% compared to the previous year.
Secondly, the development of additive manufacturing has been strongly supported by
government and it has been recognized that additive manufacturing will bring the
fourth industrial revolution. Thirdly, the huge consumer markets offer tremendous op-
portunities for 3D printing and there will be a real chance for photocuring 3D printing
from the existing 300 billion market of polymer injection molding. Most importantly,
the photocuring 3D printing technology and its materials are far away from the stage
of booming rapid growth. However, by coupling with the highly developed internet,
the photocuring 3D printing technology will develop rapidly.

References
[1] Kruth, J. P., Leu, M. C., Nakagawa, T. Progress in additive manufacturing and rapid
prototyping, CIRP Annals, 1998, 47, 525–540.
[2] Bikas, H., Stavropoulos, P., Chryssolouris, G. Additive manufacturing methods and modelling
approaches: A critical review, Int J Adv Manuf Technol, 2015, 83, 389–405.
[3] Gao, W., et al. The status, challenges, and future of additive manufacturing in engineering,
Comput-Aided Des, 2015, 69, 65–89.
[4] Huang, S. H., et al. Additive manufacturing and its societal impact: A literature review,
Int J Adv Manuf Technol 2012, 67, 1191–1203.
[5] Revilla-Leon, M., Ozcan, M. Additive manufacturing technologies used for processing
polymers: Current status and potential application in prosthetic dentistry, J Prosthodont,
2019, 28, 146–158.
[6] Ligon, S. C., et al. Polymers for 3D printing and customized additive manufacturing, Chem
Rev, 2017, 117, 10212–10290.
[7] Ngo, T. D., et al. Additive manufacturing (3D printing): A review of materials, methods,
application and challenges, Composites, Part B, 2018, 143, 172–196.
[8] Quan, H., et al. Photo-curing 3D printing technique and its challenges, Bioact Mater, 2020, 5,
110–115.
[9] Zhang, J., Xiao, P. 3D printing of photopolymers, Polym Chem, 2018, 9, 1530–1540.
[10] Hull, C. W., Uvp, I. Apparatus for production of three-dimensional objects by
stereolithography. 1986.
[11] Herzberger, J., et al. 3D Printing All-Aromatic Polyimides Using Stereolithographic 3D Printing
of Polyamic Acid Salts, ACS Macro Lett, 2018, 7, 493–497.
[12] Khatri, B., et al. Development of a multi-material stereolithography 3D printing device,
Micromachines, 2020, 11, 532.
[13] Melchels, F. P., Feijen, J., Grijpma, D. W. A review on stereolithography and its application in
biomedical engineering, Biomaterials, 2010, 31, 6121–6130.
[14] Kim, S. H., et al. Precisely printable and biocompatible silk fibroin bioink for digital light
processing 3D printing, Nat Commun, 2018, 9, 1620.
 Chapter 6 Photopolymerization and its application in 3D printing 227

[15] Shen, Y., et al. DLP printing photocurable chitosan to build bio-constructs for tissue
engineering, Carbohydr Polym, 2020, 235, 115970.
[16] Li, J., et al. Optically rewritable transparent liquid crystal displays enabled by light-driven
chiral fluorescent molecular switches, Adv Mater, 2019, 31, e1807751.
[17] Shan, J., et al. Design and synthesis of free-radical/cationic photosensitive resin applied for
3D printer with Liquid Crystal Display (LCD) irradiation, Polymers, 2020, 12, 1346.
[18] Castiaux, A. D., et al. PolyJet 3D-printed enclosed microfluidic channels without photocurable
supports, Anal Chem, 2019, 91, 6910–6917.
[19] Cazón, A., Morer, P., Matey, L. PolyJet technology for product prototyping: Tensile strength
and surface roughness properties, Proc Inst Mech Eng, Part B: J Eng Manuf, 2014, 228,
1664–1675.
[20] Xing, J. F., Zheng, M. L., Duan, X. M. Two-photon polymerization microfabrication of
hydrogels: An advanced 3D printing technology for tissue engineering and drug delivery,
Chem Soc Rev, 2015, 44, 5031–5039.
[21] Tumbleston, J. R., et al. Continuous liquid interface production of 3D objects, Science, 2015,
347, 1349–1352.
[22] Bagheri, A., Jin, J. Photopolymerization in 3D printing, ACS Appl Polym Mater, 2019, 1,
593–611.
[23] Ji, Z., et al. 3D printing of photocuring elastomers with excellent mechanical strength and
resilience, Macromol Rapid Commun, 2019, 40, e1800873.
[24] Tay, Y. W., et al. Processing and properties of construction materials for 3D printing, Mater
Sci Forum, 2016, 861, 177–181.
[25] Yagci, Y., Jockusch, S., Turro, N. J. Photoinitiated polymerization: Advances, challenges, and
opportunities, Macromolecules, 2010, 43, 6245–6260.
[26] Herzberger, J., et al. Polymer design for 3D printing elastomers: Recent advances in structure,
properties, and printing, Prog Polym Sci, 2019, 97, 101144.
[27] Ligon-Auer, S. C., et al. Toughening of photo-curable polymer networks: A review, Polym
Chem, 2016, 7, 257–286.
[28] Zhang, X., et al. Acrylate-based photosensitive resin for stereolithographic three-dimensional
printing, J Appl Polym Sci, 2019, 136, 47487.
[29] Degirmenci, M., Hepuzer, Y., Yagci, Y. One-step, one-pot photoinitiation of free radical and
free radical promoted cationic polymerizations, J Appl Polym Sci, 2002, 85, 2389–2395.
[30] Ding, R., et al. Sustainable near UV-curable acrylates based on natural phenolics for
stereolithography 3D printing, Polym Chem, 2019, 10, 1067–1077.
[31] Xu, D. M., Zhang, K. D., Zhu, X. L. A novel dendritic acrylate oligomer: Synthesis and UV
curable properties, J Appl Polym Sci, 2004, 92, 1018–1022.
[32] Iedema, P. D., et al. Photocuring of di-acrylate, Chem Eng Sci, 2018, 176, 491–502.
[33] Li, C., et al. Photopolymerization kinetics and properties of a trifunctional epoxy acrylate, Des
Monomers Polym, 2012, 16, 274–282.
[34] Wan, J., et al. A sustainable, eugenol-derived epoxy resin with high biobased content,
modulus, hardness and low flammability: Synthesis, curing kinetics and structure–property
relationship, Chem Eng J, 2016, 284, 1080–1093.
[35] Maurya, S. D., et al. A review on acrylate-terminated urethane oligomers and polymers:
Synthesis and applications, Polym Plast Technol Eng, 2017, 57, 625–656.
[36] Li, J., et al. Synthesis and properties of a low-viscosity UV-curable oligomer for three-
dimensional printing, Polymer Bulletin, 2015, 73, 571–585.
[37] Atif, M., Bongiovanni, R., Yang, J. Cationically UV-cured epoxy composites, Polymer Reviews,
2015, 55, 90–106.
228 Xiaoqun Zhu, Guoqiang Lu, Jun Nie

[38] Fouassier, J. P., et al. Photoinitiators for free radical polymerization reactions, John Wiley &
Sons, Inc, 2010, 351.
[39] Mousawi, A. A., et al. 3-Hydroxyflavone and N-phenylglycine in high performance photoinitiating
systems for 3D printing and photocomposites synthesis, Macromolecules, 2018, 51, 12,
4633–4641.
[40] Kara, M., Dadashi-Silab, S., Yagci, Y. Phenacyl ethyl carbazolium as a long wavelength
photoinitiator for free radical polymerization, Macromol Rapid Commun, 2015, 36, 2070–2075.
[41] Li, J., et al. Synthesis of furan derivative as LED light photoinitiator: One-pot, low usage,
photobleaching for light color 3D printing, Dyes Pigm, 2019, 165, 467–473.
[42] Pietrzak, M., Wrzyszczyński, A. Novel sulfur-containing benzophenone derivative as radical
photoinitiator for photopolymerization, J Appl Polym Sci, 2011, 122, 2604–2608.
[43] Tang, L., Nie, J., Zhu, X. A high performance phenyl-free LED photoinitiator for cationic or
hybrid photopolymerization and its application in LED cationic 3D printing, Polym Chem,
2020, 11, 2855–2863.
[44] Zhou, R., et al. A two-photon active chevron-shaped type I photoinitiator designed for 3D
stereolithography, Chem Commun (Camb), 2019, 55, 6233–6236.
[45] Nguyen, L. H., Straub, M., Gu, M. Acrylate-based photopolymer for two-photon
microfabrication and photonic applications, Adv Funct Mater, 2005, 15, 209–216.
[46] Kelly, B. E., et al. Volumetric additive manufacturing via tomographic reconstruction, Science,
2019, 363, 1075-+.
[47] de Beer, M. P., et al. Rapid, continuous additive manufacturing by volumetric polymerization
inhibition patterning, Science Advances, 2019, 5, eaau8723.
[48] Chen, L., et al. Highly stable thiol–ene systems: From their structure–property relationship to
DLP 3D printing, J Mater Chem C, 2018, 6, 11561–11568.
[49] Zhao, T., et al. Silicone–Epoxy‐based hybrid photopolymers for 3D printing, Macromol Chem
Phys, 2018, 219, 1700530
[50] Xiao, M., Li, Z., Nie, J. Synthesis and photopolymerization of 2-(acryloyloxy)ethyl piperidine-1-
carboxylate and 2-(acryloyloxy)ethyl morpholone-4-carboxylate, J Appl Polym Sci, 2011, 119,
1978–1985.
[51] Xiao, M., He, Y., Nie, J. Novel bisphenol a epoxide–acrylate hybrid oligomer and its
photopolymerization, Des Monomers Polym, 2012, 11, 383–394.
[52] Guerra, A. J., et al. Optimization of photocrosslinkable resin components and 3D printing
process parameters, Acta Biomater, 2019, 97, 154–161.
[53] Guo, Y., et al. Solvent-free and photocurable polyimide inks for 3D printing, J Mater Chem A,
2017, 5, 16307–16314.
[54] Macdonald, E., et al. 3D printing for the rapid prototyping of structural electronics, IEEE
Access, 2014, 2, 234–242.
[55] MacDonald, E., Wicker, R. Multiprocess 3D printing for increasing component functionality,
Science, 2016, 353, aaf2093.
[56] Bhargav, A., et al. Applications of additive manufacturing in dentistry: A review, J Biomed
Mater Res B Appl Biomater, 2018, 106, 2058–2064.
[57] Chia, H. N., Wu, B. M. Recent advances in 3D printing of biomaterials, J Biol Eng, 2015, 9, 4.
[58] Espalin, D., et al. 3D Printing multifunctionality: Structures with electronics, Int J. Adv Manuf
Technol, 2014, 72, 963–978.
[59] Leong, K. F., Cheah, C. M., Chua, C. K. Solid freeform fabrication of three-dimensional
scaffolds for engineering replacement tissues and organs, Biomaterials, 2003, 24,
2363–2378.
[60] Li, H., Tan, C., Li, L. Review of 3D printable hydrogels and constructs, Mater Des, 2018, 159,
20–38.
 Chapter 6 Photopolymerization and its application in 3D printing 229

[61] Moszner, N., Salz, U. New developments of polymeric dental composites, Prog Polym Sci,
2001, 26, 535–576.
[62] Peutzfeldt, A. Resin composites in dentistry: The monomer systems, Eur J Oral Sci, 1997, 105,
97–116.
[63] Ji, Z., et al. Facile photo and thermal two-stage curing for high-performance 3D printing of
poly(Dimethylsiloxane), Macromol Rapid Commun, 2020, 41, e2000064.
Yang-Yang Xu, Zhaofu Ding, Haibin Zhu, Yijun Zhang, Pu Xiao,
Jean Pierre Fouassier, Jacques Lalevée
Chapter 7
Dual wavelength systems in 3D printing

7.1 Introduction
3D printing, also known as additive manufacturing, is a promising technology in
producing three dimensional objects through layer-by-layer printing [1]. Since the
proposal of the concept of 3D printing in 1980s, the 3D printing technique has wit-
nessed a rapid development and has expanded its application from traditional
manufacturing field to medical, electronics, photonics, precision machinery and
other high-tech fields [2]. Among the many 3D printing techniques, photocuring 3D
printing possesses some outstanding advantages, including high printing speed,
high precision, green chemistry and smooth surface for the printed objects. Photo-
curing 3D printing (also called stereolithography) is based on photopolymerization
reaction of formulated photosensitive liquid resin upon light irradiation. Since the
photocuring process only happens at the irradiated part of the resin, it is very easy
and the printed model can be quickly separated from the liquid resin. Therefore, a
3D model can be fabricated rapidly with high precision and fast printing rate [3, 4].
As one of the earliest 3D printing techniques, photocuring 3D printing has been the
subject of intensive study and deep exploration. According to the different principles
of pattern formation and control systems, photocuring 3D printing has developed
some unique techniques, including direct laser writing (DLW), stereolithography ap-
pearance (SLA), digital light processing (DLP), liquid crystal display (LCD), multi-jet
printing (MJP), continuous liquid interface production (CLIP), holographic 3D print-
ing technology, among others [5–7].
Photochemical reactions have been extensively exploited in the fields of or-
ganic chemistry and polymer chemistry. In general, compared to traditional thermal
polymerization, light induced polymerization reaction or photopolymerization ben-
efits from environmentally friendly conditions (usually at room temperature with-
out release of volatile organic compounds), is energy saving and low cost, shows

Yang-Yang Xu, Zhaofu Ding, Haibin Zhu, College of Chemistry and Materials Science, Anhui
Normal University, Wuhu, P. R. China
Yijun Zhang, Jacques Lalevée, Université de Haute-Alsace, CNRS, Institut de Science des
Matériaux de Mulhouse (IS2M), Mulhouse, France
Pu Xiao, Research School of Chemistry, Australian National University, Canberra, Australia
Jean Pierre Fouassier, Université de Haute-Alsace

https://doi.org/10.1515/9783110570588-007
232 Yang-Yang Xu et al.

facile operation, non-invasiveness, high reaction rate (overcoming large activation

barriers in relatively short time) and monomeric conversion, and offers the possibil-
ity of orthogonal as well as excellent spatial and temporal control [8–10]. Tremen-
dous effort has been devoted over the past few years to developing light-mediated
polymerization reactions, such as free radical polymerization (FRP), cationic poly-
merization (CP), free radical promoted cationic polymerization (FRPCP) and ring
opening polymerization (ROP) [11–13]. The usage of wavelength-selective reactions
in a one-pot system can be explained as the preference of one reaction channel over
another through utilizing a specific wavelength regime. The reactions are selec-
tively inducible in response to the irradiation wavelengths; hence, multiple reac-
tions may be regulated in one pot by simply altering the irradiation wavelengths
[14, 15]. But in most published reports, only single wavelength irradiation is used to
induce just one kind of photopolymerization [16]. In particular, for sequential poly-
merizations, either a single photo trigger (at a single wavelength) or a combination
of thermal/photo trigger was utilized to control the polymer network formation [17].
Systems completely controlled by changing irradiation wavelengths have been sel-
dom reported.
Now, the most commonly and typically utilized light source for the photocuring
3D printing is the low-cost and safe violet LED@405 nm or laser [18, 19]. However, one
of the main obstacles for photocuring 3D printing is that the existing photoinitiators
cannot be fully adapted to the current irradiation wavelength of 405 nm. The develop-
ment of orthogonal photoinitiators, which allow a separate radical/cationic polymeri-
zation dependent on the wavelengths, is supposed to be a key point in broadening the
possibilities [20]. Wavelength-selective polymerization for photocuring would greatly
expand the application in 3D printing fields, but is still in its infancy. In order to stress
upon this issue, this chapter is divided into two parts. In the first part, dual wavelength
photopolymerization reactions are introduced; and in the second part, the application
of dual wavelength photochemistry in 3D printing during the last five years is further
discussed. This chapter would bring on more attention to the investigation of dual
wavelength systems in the field of photocuring 3D printing.

7.2 Dual wavelength photopolymerization reactions

7.2.1 λ-Orthogonality click pericyclic reaction for linear polymers
using lights with different wavelengths
The click chemistry, first introduced by Sharpless in 2001, possesses some unique
features: fast reaction kinetics, quantitative yield, simple product isolation without
byproducts, eco-friendly conditions, stereoselectivity, equimolarity, uphill photosen-
sitization and orthogonal reactivity [21, 22]. The λ-orthogonality of click reactions is
 Chapter 7 Dual wavelength systems in 3D printing 233

defined as the kinetic preference of one-click reaction channel by using a specific

wavelength regime. The key to achieving orthogonality in photoinduced click reac-
tions is to select appropriate moieties that are kinetically preferred by a specific wave-
length. A one-pot reaction of equimolar quantities of maleimide with two poly
(ethylene glycol) (PEG) chains carrying different maleimide-reactive endgroups, that
is, a photoactive diene (photoenol) and a nitrile imine (tetrazole), is illustrated
in Figure 7.1. Firstly, upon selective UV irradiation (310–350 nm), the maleimide com-
pound reacts exclusively with the photoenol derivative 1. After complete conversion
of the photoenol derivative 1, subsequent irradiation at another UV light (270–310
nm) activates the click reaction between maleimide and tetrazole derivative 2. Based
on light-induced click reactions performed at specific wavelengths, the λ-orthogonal
pericyclic photochemistry offers an effective avenue for synthesizing macromolecules
by addressing individual parts of an oligomer [23].

Figure 7.1: λ-orthogonal pericyclic reactions in a one-pot system consisting of a dienophile (maleimide),
a photoenol derivative 1, and a tetrazole derivative 2. Reproduced with permission from [23]. Copyright
2015 John Wiley and Sons.
234 Yang-Yang Xu et al.

7.2.2 λ-orthogonal photopolymerization of star shaped polymers

Compared to traditional linear polymers, the star-shaped polymers have a much higher
degree of branching, which can lead to some unique physical and mechanical proper-
ties [24]. Many controlled polymerization techniques have been used for the synthesis
of well-defined star polymers, such as atom transfer radical polymerization (ATRP),
reversible addition-fragmentation chain transfer (RAFT) polymerization, nitroxide
mediated polymerization (NMP) directly based on multi-arm initiators, as well as in
combination with modular ligation strategies [25]. The sequential λ-orthogonal photo-
chemistry would develop a new method for the synthesis of star polymers. A trifunc-
tional maleimide center and a bifunctional oligomer carrying two different photoactive
termini, a benzaldehyde group and a tetrazole group, are shown in Figure 7.2. A light-
induced sequence cycloaddition between benzaldehyde/ tetrazole group with malei-
mide core is realized with UV irradiation of different wavelengths. For the first reaction
path induced by low-energy UV (300–440 nm), Diels–Alder ligation of benzaldehyde to
the maleimide core is carried out first, and then with a more energetic UV light irradia-
tion (280–440 nm), subsequent tetrazole is activated, leading to the attachment of an
ene terminated polymer to the star-shaped precursor. On the contrary, for the reverse
reaction path, tetrazole is activated prior to the benzaldehyde, with a more energetic
UV light. Then, upon the irradiation of low-energy UV, the benzaldehyde ligation is se-
lectively attached to the maleimide center [26]. Interestingly, the sequential UV irradia-
tion in one-pot system allows the synthesis of two different star polymers in an
orthogonal fashion from identical starting materials. This new λ-orthogonal reaction se-
quence demonstrates the possibility of the photochemical synthesis of complex macro-
molecular architectures, based on different wavelengths.

7.2.3 Orthogonal polymerization of graft copolymers by different

visible lights

Although UV is usually used to induce photopolymerization reactions, the applica-

tion of environmentally benign visible light for photopolymerization is much more
interesting and promising, considering that intensive UV is harmful to both envi-
ronment and human body [27, 28]. A dual-wavelength visible light-regulated or-
thogonal polymerization system capable of alternating two polymerizations for the
synthesis of graft copolymers in one pot was designed. Under blue light (460 nm)
irradiation, a merocyanine-based photoacid (PAH) could act as a photocatalyst
for the ring opening polymerization (ROP) of δ-VL, a six-membered cyclic ester
δ-valerolactone. Subsequently, after the light was switched from blue to red (635 nm),
the photoinduced electron/energy transfer-reversible addition-fragmentation chain
transfer radical (PET-RAFT) polymerization of methyl acrylate (MA), catalyzed by zinc
tetraphenylporphyrin (ZnTPP), was activated. Therefore, a graft copolymer could be
 Chapter 7 Dual wavelength systems in 3D printing

Figure 7.2: Schematic illustration for the orthogonal light induced synthesis of star shaped polymers depending on different wavelengths. Adapted
with permission from [26]. Copyright 2016 Royal Society of Chemistry.
235
236 Yang-Yang Xu et al.

synthesized by combining the photoacid catalyzed ROP and ZnTPP catalyzed

PET-RAFT polymerization in one pot by alternating visible wavelengths, as shown
in Figure 7.3. Besides graft copolymers, this alternating photo-ROP and PET-RAFT
in one-pot polymerization process can also be repeated several times to produce
block copolymers [29].

Figure 7.3: Schematic illustration of one-pot sequential photo-ROP and PET-RAFT polymerization
for the synthesis of graft copolymer PMA-b-(PHEA-g-PVL) induced by alternative blue (460 nm)
and red light (635 nm) irradiation. Reproduced with permission from [29]. Copyright 2016 Royal
Society of Chemistry.

7.2.4 Interconversion of cationic and radical polymerizations

for block copolymers
Free radical polymerization and cationic polymerization make for a big share in the
photopolymerization area. The ability to combine these two polymerization mecha-
nisms in a one-pot setup and realize the facile switching of the monomer selectivity
via external stimuli provides a wonderful opportunity to modulate polymer se-
quence and structure [30]. Light, as a clean energy source and one of the most pow-
erful external stimuli, may play a crucial role in addressing this challenge [31]. It is
a great strategy to determine monomer incorporation via the specific wavelength of
light, through selective activation of either free radical or cationic polymerization
processes. In a mixture system of equimolar isobutyl vinyl ether (IBVE) and methyl
Figure 7.4: (a) Mechanism for the polymerization switching between cationic and free radical polymerization by changing wavelength; (b) Block
copolymers generated with monomer selectivity upon blue or green LED irradiation. Adapted with permission from [32]. Copyright 2017 American
Chemical Society.
Chapter 7 Dual wavelength systems in 3D printing
237
238 Yang-Yang Xu et al.

acrylate (MA), the trithiocarbonate acts as the chain transfer agent (CTA) (1), while
2,4,6-tris(p-methoxyphenyl) pyrylium tetrafluoroborate (2) and Ir(ppy)3 (3) act as
oxidizing photocatalyst and reducing photocatalyst, respectively. As shown in
Figure 7.4, the green light (520 nm) irradiation exclusively induces the cationic pho-
topolymerization, whereas the successive exposure from green light to blue light
(450 nm) could produce a tapered di-block copolymer. Notably, a multiblock copol-
ymer is created with only blue light irradiation, under the same reaction condition
[32]. Additionally, adjusting the ratios between the two photocatalysts could further
afford complementary chemical control over these two photopolymerization reac-
tions to design elaborate polymeric structures.

7.2.5 Sequential photopolymerization of IPN by UV/visible light

Interpenetrating polymer networks (IPNs) are composed of two (or more) distinct
polymer networks that are held together by mutual entanglements within the same
polymerization system [33]. For the simultaneous formation of IPN, the two polymer
networks are formed at the same time. On the contrary, for the sequential formation
of IPN, one stage network is constructed first; and then, at a later stage, swollen
unreacted moieties are reacted to form a secondary cross-linking system [34]. A pho-
tobase generator (NPPOC-TMG) and a photoinitiator (Irgacure 2959) are selected as
the appropriate pair for sequential thiol-Michael polymerization and free radical poly-
merization of acrylates upon visible/UV light irradiation, respectively. As shown
in Figure 7.5, in a nonstoichiometric thiol-acrylate system with excess acrylate, the
thiol-Michael polymerization is initiated by photobase catalyst upon exposure to

400–500 nm 365 nm

1st Stage: photobase 2nd Stage: radical

PETMP TCDDA induced loosely thiol- initiator induced highly
Michael polymer network cross-linked polymer
formation network formation

Figure 7.5: Mechanism of wavelength-selective thiol-Michael/free radical homopolymer network

formation controlled with different wavelength induction lights (400–500 nm and 365 nm).
Reproduced with permission from [35]. Copyright 2017 American Chemical Society.
 Chapter 7 Dual wavelength systems in 3D printing 239

visible light (400–500 nm) in the first stage, resulting in a loosely cross-linked net-
work. Then, for the second-stage reaction, the subsequent free radical homopolymeri-
zation of the remaining excess acrylate moieties is initiated by radical initiator upon
UV exposure (365 nm), and finally, a highly cross-linked network material is formed
with both high stiffness and high glass transition temperature [35]. In addition to the
thiol-acrylate polymerization system discussed earlier, many other types of polymer-
izations could also be controllably induced by a similar initiation system to generate
various IPN structures.

7.3 Dual wavelength systems for 3D printing

7.3.1 Spatial photopatterning of soft matter materials with two
colors of light using a photomask
The photocuring of soft matter materials has found applications spanning from tra-
ditional coatings to high-performance dental materials. Particular attention has
been paid to network systems formed from light-activated (spatially resolved) func-
tionalization step with two wavelengths independently, allowing access to dispa-
rate materials from one resist resin, simply by selecting a specific wavelength,
which is highly attractive [36, 37]. Two photoactive groups can be dimerized upon
specific wavelength: o-methyl benzaldehyde (o-MBA) upon UV and styrylpyrene
(StyP) upon visible light irradiation, respectively. Interestingly, these two dimeriza-
tion reactions are orthogonal: the dimerization of o-MBA is exclusively initiated at
330 nm, while the StyP is solely dimerized at 435 nm. In other words, each wave-
length is highly selective towards a specific photoligation reaction within the resist,
and the shorter wavelength cannot induce ligation of the longer wavelength selec-
tive species within the same resist mixture, and vice versa. Therefore, the selective
dimerization of these two reactive species, that is, o-MBA or StyP attached to poly
(methyl methacrylate) (PMMA) chains, can induce the exclusive network formation
of one polymer component, as shown in Figure 7.6. This orthogonal photodimeriza-
tion technology allows selective curing of one out of the two soft matter materials
by simply selecting the irradiation wavelength [38]. For each wavelength, one half
of the photomask is blocked, resulting in spatially resolved patterns in predeter-
mined areas. This dual-color addressable resist system can find a vast application
ranging from coatings to 3D additive manufacturing of multimaterial architectures
by simply selecting the curing wavelength.
 240
Yang-Yang Xu et al.

Figure 7.6: Laterally resolved patterning of the wavelength-orthogonal multimaterial resist with a photomask by two colors of light: UV (λ1 = 330 nm) for
o-MBA and visible light (λ2 = 435 nm) for StyP, respectively. Adapted with permission from [38]. Copyright 2019 Wiley-Blackwell.
 Chapter 7 Dual wavelength systems in 3D printing 241

7.3.2 3D printing of polydiacetylene (PDA) photocomposite

materials: 2 wavelengths for 2 orthogonal chemistries
Polydiacetylene (PDA), whose backbone is composed of alternating ene-yne conju-
gated structure, is well known for its outstanding chromatic transition (usually
from blue to red) and fluorescence enhancement effects upon exposure to various
environmental stimuli, including heat, pH, organic solvents, biomolecular affinity,
and so on [39]. However, due to its innate weak mechanical strength, the spatially
controllable photopolymerization and subsequent 3D printing of PDA has seldom
been reported, in spite of the traditional photomask method [40]. Therefore, the
preparation of PDA photocomposite materials based on polyacrylate is first reported
by taking advantage of the dual wavelengths photopolymerization strategy and
orthogonal chemistry. Firstly, the diacetylene (DA) microaggregates are homo-
geneously dispersed in acrylate resin. Then, a visible LED@405 nm is used for the
free radical polymerization of polyacrylate. Finally, UV irradiation is used to induce
the 1,4-topotactic polymerization of PDA, which can illustrate a successive blue-to-
purple-to-red colorimetric transition, in response to increment in the temperature
gradient. Interestingly and more importantly, thanks to the acrylate matrix resin,
3D printing technique can be applied directly to this composite material, in a laser
dioxide at 405 nm and UV combination, and successfully realizes the spatially con-
trolled polymerization of PDA (Figure 7.7). Using this method, many macroscop-
ically three dimensional patterns can be fabricated with high resolution, which also

Figure 7.7: Numerical optical microscopy observation of the 3D printing stereo pattern: (a) top
surface morphology; (b) 3-D overall appearance in color pattern, respectively. (c) In-situ
photographs of the generated stereo patterns: UV- induced topopolymerization of PDA and
following colorimetric change from blue to red upon heated to 80 °C (from left to right).
Reproduced with permission from [41]. Copyright 2020 American Chemical Society.
242 Yang-Yang Xu et al.

show thermochromic behavior [41]. This novel kind of functional photocomposite

material demonstrates a wide application prospect in various fields, such as laser
writing, colorimetric sensing, information encryption, anti-counterfeiting, and so on.

7.3.3 Continuous and rapid additive manufacturing by volumetric

polymerization inhibition patterning

Traditional layer-wise additive manufacturing approaches often yield objects with

ridged surfaces and at sluggish fabrication rates. Use of continuous stereolitho-
graphic printing can overcome the disadvantages of layer-wise operation and gen-
erate objects that have smooth surfaces and achievable high printing speeds [42,
43]. In a complex photoinitiating system, camphorquinone (CQ) and ethyl 4-(dime-
thylamino)benzoate (EDAB) act as a visible-light photoinitiator and co-initiator,
while bis[2-(o-chlorophenyl)- 4,5-diphenylimidazole] (o-Cl-HABI) acts as a UV pho-
toinhibitor, respectively. Therefore, the polymerization of acrylate resin can be se-
lectively initiated with blue light (458 nm) irradiation and inhibited by UV light
(365 nm), in the presence of the complementary photoinitiator and photoinhibitor
species. A unique feature of this method can achieve volumetric patterning through
the usage of a multicolor system (UV and blue light) with both polymerization initi-
ation and polymerization inhibition species. The thickness of the polymerization in-
hibition volume can be controlled by varying the ratio of the intensities of the two
illuminating light sources and the concentration of the UV absorber. When both UV
and blue light are supplied to the resin, an inhibition volume with no polymeriza-
tion is generated adjacent to the window. Above this region, polymerization occurs,
allowing the continuous printing of objects. Notably, in conjunction with high pho-
toinitiation rates, the large inhibition volume can facilitate continuous and rapid
object printing [44]. The proposed concurrent photoinitiation and photoinhibition
process overcomes numerous time-consuming steps currently used in micro fabri-
cation, and allows single-step fabrication of cured materials with intricate surface
topographies and rapid generation of personalized 3D products.

7.3.4 One-step, multimaterial 3D printing by solution mask liquid

lithography
Traditional objects printing systems use only a single starting material, while multi-
material printing (e.g., polymer–polymer composites) can be particularly attractive
in designing advanced materials with unique properties. The development of effec-
tive mixture resins incorporating multiple photochemical reactions that allow spa-
tial resolution and orthogonal cross-linking has been a major challenge to realize
this goal [45, 46]. The solution mask liquid lithography (SMaLL) approach can be
 Chapter 7 Dual wavelength systems in 3D printing 243

used for the fabrication of 3D objects with spatially resolved mechanical and chemi-
cal properties. This novel methodology takes advantage of coherent photobleaching
fronts arising from the use of photochromic molecules (solution masks) to provide
rapid build rates, large depths of cure without the need for moving parts, excellent
feature resolution and 3D objects without layering defects. In a mixture resin sys-
tem, camphorquinone (CQ) is examined as the photosensitizer, since it is capable of
inducing both radical and cationic polymerizations. Through wavelength-selective
activation, blue light (λmax ≈ 470 nm) or green light (λmax ≈ 530 nm), this SMaLL
methodology is used to induce selective radical/cationic dual photocuring, produc-
ing 3D objects with a range of mechanical properties (≈4 orders of magnitude variation
in moduli) from commercially viable monomer systems. The coupling of these photo-
switches with resin mixtures containing orthogonal photo-cross-linking systems allows
simultaneous and selective curing of multiple networks, providing access to 3D objects
with chemically and mechanically distinct domains. The versatility of the SMaLL
method can be demonstrated through the fabrication of a bioinspired butterfly tem-
plate, which has soft and flexible joints to connect the stiff and structural “wings” and
“body” parts, as shown in Figure 7.8. Interestingly, upon application of tension to the
“wings,” local strain and flexing is observed selectively in the flexible, acrylate-based
joint regions while the “body” and “wings” remain rigid due to the stiff epoxy domains
[47].

Mixed resin
470 nm Exposure 530 nm Exposure

Unreacted
cationic
monomer

Stiff, glassy Soft, rubbery

dual cationic/radical radical only
(a) (b) (c) (d)
Stiff, structural
Soft, flexible Local
strain

2 mm
Soft joints

Figure 7.8: (Up) Schematic illustration of network structure formation: blue exposure (470 nm)
leads to dual radical and cationic curing, while green exposure (530 nm) results in only radical
cross-linking. (Down) Digital butterfly design: blue areas correlate to stiff sections and green
areas correlate to soft joints. Adapted with permission from [47]. Copyright 2018 Wiley-Blackwell.
244 Yang-Yang Xu et al.

7.3.5 Multimaterial actinic spatial control with UV/visible light

Additive manufacturing could make production of multimaterial objects with varied

mechanical properties possible. However, achieving multimaterial control along all
three axes of printing [48, 49] still remains a huge challenge. A multiwavelength
photopolymerization method utilizing multimaterial actinic spatial control (MASC)
during additive manufacturing is developed to provide chemoselective wavelength
control over material composition. Notably, the radical and cationic photopolymeriza-
tion of acrylate and epoxide can be viewed as orthogonal upon different wavelengths
with specific photoinitiators. Figure 7.9 shows a multicomponent photoresin includ-
ing both acrylate- and epoxide-based monomers as well as corresponding radical and
cationic photoinitiators. Specifically, under long wavelength (visible light) irradiation,
the Irgacure initiator (Irgacure 819) can be selectively activated, leading to prefer-
ential curing of acrylate-based resin components with free radical polymerization

Figure 7.9: (a) MASC formulation for the synthesis of multimaterials with different wavelengths of
light; (b) computer-aided design (CAD) model; and (c) printed tetragonal lattice: purple part
corresponds to regions printed with UV light and white/grey part corresponds to visible light.
Adapted with permission from [50]. Copyright 2019 Nature Publishing Group.
 Chapter 7 Dual wavelength systems in 3D printing 245

mechanism; however, under short wavelength (UV) irradiation, a combination of

free radical polymerization and cationic polymerization is observed. This wave-
length-dependent photopolymerization enables the production of multimaterials
containing both stiff epoxide networks and flexible, elastomeric acrylate parts.
Also, the variation in the photoresin formulation with different wavelengths can
drastically adjust the mechanical properties of printed samples. In a tetragonal
lattice design, the x-axis is printed with UV light to produce stiff rows, the z-axis
is prepared predominately with visible light to produce a viscoelastic part, while
the y-axis is printed with either UV or visible light to provide a composite re-
sponse. Compression along these three axes reveals different degrees of stiffness
and flexibility [50]. Besides, the spatially controlled swelling behavior of the
printed objects through the MASC method can create multimaterial actuators for
the purpose of 4D printing, considering the various swelling ratios in deionized
water or organic solvents for the multimaterials components fabricated with either
UV or visible light.

7.4 Conclusions and perspectives

3D printing techniques are now quite well established. However, for the photopoly-
merization approaches, it mainly depends on the use of a single wavelength
(@405 nm). We have shown here that the use of multiple wavelengths can be very
attractive for the introduction of new functionalities in 3D printed materials. Al-
though this approach remains in an infant stage, important developments are un-
derway, leading to new materials.

References
[1] Tay, Y. W., Panda, B., Paul, S. C., Tan, M. J., Qian, S., Leong, K. F., Chua, C. K. Processing and
properties of construction materials for 3D printing, Mater Sci Forum, 2016, 861, 177–181.
[2] Quan, H., Zhang, T., Xu, H., Luo, S., Nie, J., Zhu, X. Photo-curing 3D printing technique and its
challenges, Bioact Mater, 2020, 5, 110–115.
[3] Sanders, P., Young, A. J., Qin, Y., Fancey, K. S., Reithofer, M. R., Guillet-Nicolas, R., Kleitz, F.,
Pamme, N., Chin, J. M. Stereolithographic 3D printing of extrinsically self-healing
composites, Sci Rep, 2019, 9, 388.
[4] Wang, X., Jiang, M., Zhou, Z., Gou, J., Hui, D. 3D printing of polymer matrix composites: A
review and prospective, Compos Part B, 2017, 110, 442–458.
[5] Ji, Z., Zhang, X., Yan, C., Jia, X., Xia, Y., Wang, X., Zhou, F. 3D printing of photocuring
elastomers with excellent mechanical strength and resilience, Macromol Rapid Commun,
2019, 40, 1800873.
[6] Liu, Y., Lin, Y., Jiao, T., Lu, G., Liu, J. Photocurable modification of inorganic fillers and their
application in photopolymers for 3D printing, Polym Chem, 2019, 10, 6350–6359.
246 Yang-Yang Xu et al.

[7] Guo, Y., Ji, Z., Zhang, Y., Wang, X., Zhou, F. Solvent-free and photocurable polyimide inks for
3D printing, J Mater Chem A, 2017, 5, 16307–16314.
[8] Jasinski, F., Zetterlund, P. B., Braun, A. M., Chemtob, A. Photopolymerization in dispersed
systems, Prog Polym Sci, 2018, 84, 47–88.
[9] Kasisomayajula, S., Jadhav, N., Gelling, V. J. Conductive polypyrrole and acrylate
nanocomposite coatings: Mechanistic study on simultaneous photopolymerization, Prog Org
Coat, 2016, 101, 440–454.
[10] Chemtob, A., Feillée, N., Ley, C., Ponche, A., Rigolet, S., Soraru, C., Ploux, L., Nouen,
D. L. Oxidative photopolymerization of thiol-terminated polysulfide resins. Application in
antibacterial coatings, Prog Org Coat, 2018, 121, 80–88.
[11] Riad, K. B., Arnold, A. A., Claverie, J. P., Hoa, S. V., Wood-Adams, P. M. Photopolymerization
using metal oxide semiconducting nanoparticles for epoxy-based coatings and patterned
films, ACS Appl Nano Mater, 2020, 3, 2875–2880.
[12] Wang, D., Szillat, F., Fouassier, J. P., Lalevée, J. Remarkable versatility of Silane/Iodonium
salt as redox free radical, cationic, and photopolymerization initiators, Macromolecules,
2019, 52, 5638–5645.
[13] Hola, E., Pilch, M., Galek, M., Ortyl, J. New versatile bimolecular photoinitiating systems
based on amino-m-terphenyl derivatives for cationic, free-radical and thiol-ene
photopolymerization under low intensity U -A and visible light sources, Polym Chem, 2020,
11, 480–495.
[14] Eibel, A., Fast, D. E., Sattelkow, J., Zalibera, M., Wang, J., Huber, A., Müller, G., Neshchadin,
D., Dietliker, K., Plank, H., Grützmacher, H., Gescheidt, G. Star-shaped polymers through
simple wavelength -selective free radical photopolymerization, Angew Chem Int Ed, 2017,
56, 14306–14309.
[15] Kaupp, M., Hiltebrandt, K., Trouillet, V., Mueller, P., Quick, A. S., Wegener, M., Barner-
Kowollik, C. Wavelength selective polymer network formation of end-functional star
polymers, Chem Commun, 2016, 52, 1975–1978.
[16] Zhang, J., Hill, N. S., Lalevée, J., Fouassier, J.-P., Zhao, J., Graff, B., Schmidt, T. W., Kable,
S. H., Stenzel, M. H., Coote, M. L., Xiao, P. Multihydroxy-anthraquinone derivatives as free
radical and cationic photoinitiators of various photopolymerization under green LED,
Macromol Rapid Commun, 2018, 39, 1800172.
[17] Wang, D., Kaya, K., Garra, P., Fouassier, J.-P., Graff, B., Yagci, Y., Lalevée, J. Sulfonium salt
based charge transfer complexes as dual thermal and photochemical polymerization
initiators for composites and 3D printing, Polym Chem, 2019, 10, 4690–4698.
[18] Dumur, F., Gigmes, D., Fouassier, J.-P., Lalevée, J. Organic electronics: An El dorado in the
quest of new photocatalysts for polymerization reactions, Acc Chem Res, 2016, 49,
1980–1989.
[19] Sun, K., Xu, Y., Dumur, F., Morlet-Savary, F., Chen, H., Dietlin, C., Graff, B., Lalevée, J., Xiao,
P. In silico rational design by molecular modeling of new ketones as photoinitiators in three-
component photoinitiating systems: Application in 3D printing, Polym Chem, 2020, 11,
2230–2242.
[20] Hurrle, S., Lauer, A., Gliemann, H., Mutlu, H., Wöll, C., Goldmann, A. S., Barner-Kowollik,
C. Two-in-one: λ-orthogonal photochemistry on a radical photoinitiating system, Macromol
Rapid Commun, 2017, 38, 1600598.
[21] Kolb, H. C., Finn, M. G., Sharpless, K. B. Click chemistry: Diverse chemical function from a few
good reactions, Angew Chem Int Ed, 2001, 40, 2004–2021.
[22] Lutz, J.-F. 1,3-Dipolar cycloadditions of azides and alkynes: A universal ligation tool in
polymer and materials science, Angew Chem Int Ed, 2007, 46, 1018–1025.
 Chapter 7 Dual wavelength systems in 3D printing 247

[23] Hiltebrandt, K., Pauloehrl, T., Blinco, J. P., Linkert, K., Borner, H. G., Barner-Kowollik, C.
λ-Orthogonal pericyclic macromolecular photoligation, Angew Chem Int Ed, 2015, 54,
2838–2843.
[24] Chaffey-Millar, H., Stenzel, M. H., Davis, T. P., Coote, M. L., Barner-Kowollik, C. Design
criteria for star polymer formation processes via living free radical polymerization,
Macromolecules, 2006, 39, 6406–6419.
[25] Wenn, B., Martens, A. C., Chuang, Y. M., Gruber, J., Junkers, T. Efficient multiblock star
polymer synthesis from photo-induced copper-mediated polymerization with up to 21 arms,
Polym Chem, 2016, 7, 2720–2727.
[26] Hiltebrandt, K., Kaupp, M., Molle, E., Menzel, J. P., Blinco, J. P., Barner-Kowollik, C. Star
polymer synthesis via λ-orthogonal photochemistry, Chem Commun, 2016, 52, 9426–9429.
[27] Qiu, W., Li, M., Yang, Y., Li, Z., Dietliker, K. Cleavable coumarin-based oxime esters with
terminal heterocyclic moieties: Photobleachable initiators for deep photocuring under visible
LED light irradiation, Polym Chem, 2020, 11, 1356–1363.
[28] Li, Y.-H., Chen, Y.-C. Triphenylamine-hexaarylbiimidazole derivatives as hydrogen-acceptor
photoinitiators for free radical photopolymerization under UV and LED light, Polym Chem,
2020, 11, 1504–1513.
[29] Fu, C., Xu, J., Boyer, C. Photoacid-mediated ring opening polymerization driven by visible
light, Chem Commun, 2016, 52, 7126–7129.
[30] Chen, M., Deng, S., Gu, Y., Lin, J., MacLeod, M. J., Johnson, J. A. Logic-controlled radical
polymerization with heat and light: Multiple-stimuli switching of polymer chain growth via a
recyclable, thermally responsive gel photoredox catalyst, J Am Chem Soc, 2017, 139,
2257–2266.
[31] Xu, J., Shanmugam, S., Fu, C., Aguey-Zinsou, K.-F., Boyer, C. Selective photoactivation: From
a single unit monomer insertion reaction to controlled polymer architectures, J Am Chem Soc,
2016, 138, 3094–3106.
[32] Kottisch, V., Michaudel, Q., Fors, B. P. Photocontrolled interconversion of cationic and radical
polymerizations, J Am Chem Soc, 2017, 139, 10665–10668.
[33] Hola, E., Ortyl, J., Jankowska, M., Pilch, M., Galek, M., Morlet-Savary, F., Graff, B., Dietlinc, C.,
Lalevée, J. New bimolecular photoinitiating systems based on terphenyl derivatives as highly
efficient photosensitizers for 3D printing application, Polym Chem, 2020, 11, 922–935.
[34] Tehfe, M. A., Lalevee, J., Telitel, S., Contal, E., Dumur, F., Gigmes, D., Bertin, D., Nechab, M.,
Graff, B., Morlet-Savary, F., Fouassier, J. P. Polyaromatic structures as organo-photoinitiator
catalysts for efficient visible light induced dual radical /cationic photopolymerization and
interpenetrated polymer networks synthesis, Macromolecules, 2012, 45, 4454–4460.
[35] Zhang, X., Xi, W., Huang, S., Long, K., Bowman, C. N. Wavelength-selective sequential
polymer network formation controlled with a two-color responsive initiation system,
Macromolecules, 2017, 50, 5652–5660.
[36] Gräfe, D., Wickberg, A., Zieger, M. M., Wegener, M., Blasco, E., Barner-Kowollik, C. Adding
chemically selective subtraction to multi-material 3D additive manufacturing, Nat Commun,
2018, 9, 2788.
[37] Liang, Y., Kiick, K. L. Multifunctional lipid-coated polymer nanogels crosslinked by photo-
triggered Michael-type addition, Polym Chem, 2014, 5, 1728–1736.
[38] Bialas, S., Michalek, L., Marschner, D. E., Krappitz, T., Wegener, M., Blinco, J., Blasco, E.,
Frisch, H., Barner-Kowollik, C. Access to disparate soft matter materials by curing with two
colors of light, Adv Mater, 2019, 31, 1807288.
[39] Weston, M., Tjandra, A. D., Chandrawati, R. Tuning chromatic response, sensitivity, and
specificity of polydiacetylene-based sensors, Polym Chem, 2020, 11, 166–183.
248 Yang-Yang Xu et al.

[40] Lee, J., Seo, S., Kim, J. Rapid light-driven color transition of novel photoresponsive
polydiacetylene molecules, ACS Appl Mater Interfaces, 2018, 10, 3164–3169.
[41] Xu, -Y.-Y., Ding, Z.-F., Liu, F.-Y., Sun, K., Dietlin, C., Lalevée, J., Xiao, P. 3D printing of
polydiacetylene photocomposite materials: Two wavelengths for two orthogonal chemistries,
ACS Appl Mater Interfaces, 2020, 12, 1658–1664.
[42] Tumbleston, J. R., Shirvanyants, D., Ermoshkin, N., Janusziewicz, R., Johnson, A. R., Kelly, D.,
Chen, K., Pinschmidt, R., Rolland, J. P., Ermoshkin, A., Samulski, E. T., DeSimone,
J. M. Continuous liquid interface production of 3D objects, Science, 2015, 347, 1349–1352.
[43] Zhu, W., Tringale, K. R., Woller, S. A., You, S., Johnson, S., Shen, H., Schimelman, J.,
Whitney, M., Steinauer, J., Xu, W., Yaksh, T. L., Nguyen, Q. T., Chen, S. Rapid continuous 3D
printing of customizable peripheral nerve guidance conduits, Mater Today, 2018, 21,
951–959.
[44] Beer, M. P., Laan, H. L., Cole, M. A., Whelan, R. J., Burns, M. A., Scott, T. F. Rapid, continuous
additive manufacturing by volumetric polymerization inhibition patterning, Sci Adv, 2019, 5,
eaau8723.
[45] Studart, A. R. Additive manufacturing of biologically-inspired materials, Chem Soc Rev, 2016,
45, 359–376.
[46] Compton, B. G., Lewis, J. A. 3D-printing of lightweight cellular composites, Adv Mater, 2014,
26, 5930–5935.
[47] Dolinski, N. D., Page, Z. A., Callaway, E. B., Eisenreich, F., Garcia, R. V., Chavez, R., Bothman,
D. P., Hecht, S., Zok, F. W., Hawker, C. J. Solution mask liquid lithography (SMaLL) for one-
step, multimaterial 3D printing, Adv Mater, 2018, 30, 1800364.
[48] Shusteff, M., Browar, A. E. M., Kelly, B. E., Henriksson, J., Weisgraber, T. H., Panas, R. M.,
Fang, N. X., Spadaccini, C. M. One-step volumetric additive manufacturing of complex
polymer structures, Sci Adv, 2017, 3, eaao5496.
[49] Nadgorny, M., Ameli, A. Functional polymers and nanocomposites for 3D printing of smart
structures and devices, ACS Appl Mater Interfaces, 2018, 10, 17489–17507.
[50] Schwartz, J. J., Boydston, A. J. Multimaterial actinic spatial control 3D and 4D printing, Nat
Commun, 2019, 10, 791.
Xuewen Wang, Yunfan Yue, Nianyao Chai, Yibing Chen
Chapter 8
Functional 3D nanoprinting via femtosecond
laser nonlinear lithography
8.1 Introduction
Continuous development in the field of three-dimensional (3D) additive manufactur-
ing (AM) techniques makes it possible to generate complex geometry 3D structure [1].
Driven by femtosecond direct laser writing (fs-DLW) via nonlinear lithography, the
technology has reached a new level, where printing accurate and complex 3D struc-
tures in the micro/nanometer scale can be considered [2]. Up to now, it has been
widely used in the fields of science and engineering, in fabrication of dielectric geo-
metric phase optical elements, laser plasmonic coloration of metal films and laser di-
rect printing meta-atom structures [3–6].
Currently, Two-photon lithography (TPL) via femtosecond laser is the efficient
way for fabricating complex architectures, with the resolution beyond the diffrac-
tion limit [7, 8]. TPL induced by nonlinear absorption contains two critical steps:
two-photon absorption and two-photon polymerization [9]. Photoresist is a key ma-
terial involved in these two steps. Its solubility will change under exposure to elec-
tron beam, ion beam or femtosecond laser beam, etc., so as to achieve the targeted
structures. According to the photochemical reaction mechanism, photoresist can be
divided into two categories: positive and negative photoresist, whose solubility is
increased or decreased after laser exposure. Different types of photoresists and
their applications will be discussed in Section 4.
As a simple way to fabricate function materials at micro/nanometer scale, TPL
has attracted broad interest [10]. In order to fabricate more precise and controllable
structures rationally, a variety of 3D printing technologies have developed, such as
inkjet printing, selective laser sintering (SLS) and selective laser melting (SLM) [1].

Xuewen Wang, International School of Materials Science and Engineering, Wuhan University of
Technology, Wuhan, P. R. China; Foshan Xianhu Laboratory of the Advanced Energy Science and
Technology, Guangdong Laboratory, Foshan, P. R. China; State Key Laboratory of Advanced
Technology for Materials Synthesis and Processing, Wuhan University of Technology, Wuhan,
P. R. China
Yunfan Yue, Nianyao Chai, International School of Materials Science and Engineering, Wuhan
University of Technology, Wuhan, P. R. China; State Key Laboratory of Advanced Technology for
Materials Synthesis and Processing, Wuhan University of Technology, Wuhan, P. R. China
Yibing Cheng, Foshan Xianhu Laboratory of the Advanced Energy Science and Technology,
Guangdong Laboratory, Foshan, P. R. China; State Key Laboratory of Advanced Technology for
Materials Synthesis and Processing, Wuhan University of Technology, Wuhan, P. R. China

https://doi.org/10.1515/9783110570588-008
250 Xuewen Wang et al.

However, when compared to these technologies, TPL has more advantages. One is
able to achieve controllable spatial resolution beyond diffraction limit [11, 12]. In
terms of manufacturing accuracy, the process is no longer layer-to-layer, but bot-
tom-up through moving the focal spot, which avoids precision deviations due to
layer thickness. Another advantage is that the extensive materials can be used via
this technique. As long as TPL technique uses photoinitiators and monomers, theo-
retically, a variety of materials can be photopolymerized for designed properties.
In this chapter, we will focus on the functional 3D nanoprinting technique via
TPL, starting from the theory to emerging applications. This systematic interpreta-
tion is helpful for readers to build a comprehensive understanding of the existing
literature on this technology.

8.2 Classical theory

8.2.1 Multiphoton absorption process

Multiphoton absorption is an optical phenomenon behind the TPL process. Simply,

we will concentrate on two-photon absorption (TPA) which can be easily extrapo-
lated to other number of photons. The concept of TPA, which was a two-order
nonlinear optical absorption, was born in 1931, with the seminal paper of Goeppert-
Mayer et al. [13]. It is defined as “an absorption event caused by the collective action of
two or more photons, all of which must be present simultaneously to impart enough
energy to drive a transition” [13]. But, limited by technology and equipment, this
concept was not experimentally verified over 30 years, until the emergence of la-
sers, by Kaiser and Garret [14]. However, the lack of large TPA cross-section materials
(<10−48cm4 · s/photon) [15] also inhibited the ongoing research. In the 1990s, organic
photoresists with large TPA cross section were gradually discovered, and the technol-
ogies related to TPA have also begun to enter a period of rapid development [16].
As for single-photon absorption, the molecule makes a transition from ground
state to the excited state through absorbing a photon. TPA means that the mole-
cule needs to absorb two photons in a short time to obtain sufficient energy to
complete the transition process. There are two types of TPA process: sequential
and simultaneous absorption (Figure 8.1) [9]. In sequential absorption, the mole-
cule is excited to a real intermediate state by absorbing one of the photons; then,
the second is absorbed. In simultaneous absorption, a virtual intermediate energy
state is reached where the first photon is absorbed. Only if the second photon is
absorbed in an extremely short time can the molecule reach the excited state [17].
In this situation, the molecule can be excited from the ground state S0 to the state
S1, S2 or Sn through virtual state, and then it returns to the state S1 through non-
radiation state [18].
 Chapter 8 Functional 3D nanoprinting via femtosecond laser nonlinear lithography 251

S2 or Sn

Non-radiation state

S1 S1
hν

Photon 2hν

Virtual state
Photons

hν

Photon Figure 8.1: The schematic

S0 S0 process of two-photon
absorption with energy
Sequential Simultaneous transitions [9].

If the two photons have the same energy, the square of the intensity of the laser
beam determines the transition probability for the TPA process. On the contrary, if
they have different energies, the transition probability is relative to the product of
the intensities of the two laser beams. This characteristic explains that TPA absorp-
tion only generates in the focal region of the laser beam.

8.2.2 Two-photon polymerization process

TPP is a specific phenomenon of polymerization reaction between monomers after

photoinitiators are excited by TPA. The photoinitiator (also called photosensitizer)
cannot generate radicals until photons are captured, after which it will transfer en-
ergy to the unpolymerized monomers to initiate polymerization [19]. There are three
steps during TPP as shown in Figure 8.2 [20, 21].

I hν I* R.
First step Photon-initiation

Second step Chain reaction R.+M RM. RMM. .... RMMn.

RMn. + RMm. RMm+nR

Third step Termination reaction

RMn. + RMm. RMn + RMm

Figure 8.2: The reaction for two-photon polymerization. I, I*, R · are photoinitiator, intermediate
state of the photoinitiator after absorbing a photon and radical, respectively. M is the monomer or
oligomer unit. Mn, Mm and Mm +n represent different degrees of polymerization [20,21].
252 Xuewen Wang et al.

First, a tightly focused beam is irradiated inside the photoresist, so the photon
density at the focal spot is extremely high. The photoinitiator in the excited state and
the initiator energy conversion or electron transfer occurs between the agents, and
an initiator generates active free radicals. Later, free radicals continue to combine
with unsaturated groups in the polymer material to generate monomer radicals, and
they are combined with new monomers again, which results in the chain growing up
rapidly. Lastly, the monomer radical expands in the chain reaction until two radicals
meet. A solid polymer is formed, and the reaction is terminated as soon as two free
radicals meet and combine. The final result of photopolymerization is the depletion
of free radicals or other components. Besides, other reactions also often take place
and complicate the principles of free radical polymerization such as chain transfer
and chain inhibition.
Above all, there are two conditions for TPP: external and internal. For external, it
should have enough light intensity to induce TPA and initiate photopolymerization. A
tightly focused femtosecond laser beam can generate GW-level instantaneous power at
a very low average power and has good spatial selectivity [22]. Therefore, it is consid-
ered to be a critical approach for two-photon polymerization. For internal, the material
is specific with two-photon absorption characteristics [23]. Organic or hybrid photo-
polymer materials containing initiators with large two-photon absorption cross sections
are commonly used for two-photon polymer photoresist (such as SU-8, SZ-2080) [7].
The general scheme for polymerization also fits for photopolymerization, and obviously
it has certain advantages in high reaction rate at room temperature and the spatial con-
trol of the polymerization process.

8.3 Femtosecond laser-based micro/nano fabrication

As an indispensable technology for high accuracy structuring, TPL is powerful and
has the potential for achieving designed three-dimensional structures with submi-
cron resolution [9]. The exposure time, laser power and the type of photoresists de-
termine the resolution and scale of structures to a large extent. In this section, we
will describe the lithography process and theoretical equation of feature size for
identifying the correlation between controllable resolution and these parameters.

8.3.1 Printing system and manufacturing process

For rapid fabrication of flexible 3D structures, TPL of photoresists is a typical exam-

ple and has emerged as an effective technique to achieve micro/nanometer spatial
resolution [24, 25]. The photopolymerization process can be initiated by TPA within
the focal region when an ultrafast laser beam is tightly focused on a volume of
 Chapter 8 Functional 3D nanoprinting via femtosecond laser nonlinear lithography 253

photosensitive material. The complex 3D structures can be fabricated accurately

through moving the focal spot in 3D direction inside photoresists. After that, the
other step is to wash and remove the nonilluminated and nonpolymerized region.
In Figure 8.3, a typical TPL experimental setup is shown Reference [26], which
includes (i) an ultrafast laser system, (ii) beam focusing optics, (iii) a beam deflec-
tion or (and) sample motion system, (iv) a beam shutter and an attenuator, and (v)
a set of computer control software.

Figure 8.3: Schematic of a typical TPL system [26].

(i) The ultrafast laser could be a Ti:Sapphire femtosecond oscillator providing the
laser source for the whole fabrication system. Recently, the device has been de-
signed to generate more than one wavelength of laser source to satisfy more
demands.
(ii) The high intensity is required for TPA and a tightly focused laser beam is indis-
pensable for high structuring resolution, thus a microscope objective has to be
used to reduce the spot radius. The critical parameter of the objective is the nu-
merical aperture (N.A.), which controls the resolution and the scale of structures.
(iii) Motion system determines the dimension and processing efficiency of fabrica-
tion. The advantage of this system is that there is no need to slice the designed
structure when using a xyz stage for structure printing, as the stage and objective
are able to move in all directions, which leads the focal spot to any location.
254 Xuewen Wang et al.

(iv) It is possible to switch the beam on/off rapidly by using an ultrafast shutter.
Besides, the attenuator can accurately control the beam intensity using neutral
density filters.
(v) The software, which synchronizes the optical and mechanical components
mentioned, is also one of the most important parts in the whole system. At the
same time, excellent software can optimize the laser moving path to reduce dis-
placement, which actualizes high fabrication efficiency.

8.3.2 Printing resolution

The main advantage of additive manufacturing (AM) is that the internal geometry
of the structure/pattern has large freedom and can reduce the waste of raw materi-
als when manufacturing. By improving the technology of TPL, the flexibility and
complexity of architectures can be increased, and the feature size can reach a
higher level, because the accuracy can be adjusted by external conditions [27, 28].
The resolution of fabricated structures is relevant to the unit of TPP voxels or
lines. As we know, there are two main scanning modes in fabricating. One is pin-
pointing scanning (spot-evaluation) mode, where the feature size is voxels. The other
one is the continuing scanning (or line scanning) mode, where feature size is line
width. Since the intensity of the laser beam is approximately treated as a Gaussian
distribution, the shape of voxels is an ellipsoid [29], so the feature size of voxels in-
cludes the lateral (d) and axial (l). The ratio between them called aspect ratio (AR, α),
that is, α = l/d, has also been explored by many researchers [27, 28, 30].
In order to get more specific knowledge of resolution controlling, a suitable
equation should be used to describe the shape of focal spot. The electric field inten-
sity (E) of the laser beam is shown in eq. (8.1) [31] as follows:
!
ωo r2
Eðr, zÞ = E0 * *exp − 2 (8:1)
ωðzÞ ωð z Þ

where ω(0) is the waist (radius) of beam (z = 0), and ω(z) is the waist of beam at
plane z; r and z are distance along the cross-section from center and axial distance
along the focal plane, respectively. E0 is the central electric field strength.
In the optical field of laser beam, the relationship between central electric inten-
sity (E0) and the photon flux intensity(I0) is IO ∝ E02 . Hence, according to the eq. (8.1),
the distribution of photon flux intensity I(r, z) at the distances of r and z to center
and focal plane, respectively, can be expressed as follows [32]:
  !
ωo 2 2r2
I ðr, zÞ = I0 * *exp − 2 (8:2)
ωð z Þ ωð z Þ
 Chapter 8 Functional 3D nanoprinting via femtosecond laser nonlinear lithography 255

The average photon flux intensity at the focus plane Ifocus is shown as follows [27]:

P
Ifocus = (8:3)
πω0 τfhν

in which P, τ, f, h, ν are the average laser power, pulse width, repetition frequency,
Planck constant and laser frequency, respectively. According to ν = c/λ, it can calcu-
late the light frequency, where c and λ denote the speed of light and the wavelength
of the laser beam. We can use Ifocus to define I0 as follows [27]:

2e2
Io = Ifocus ≈ 2.3Ifocus (8:4)
e2 − 1
Combining eqs. (8.2)–(8.4), the distribution of photon flux intensity can be expressed
by the experimental parameters. In TPL system, an objective lens was always used to
focus the beam. Thus, when a low N.A. (N.A. ≤ 1) is used, the ω0 can be expressed as:

λ
ω0 = (8:5)
π*NA

But, it is inapplicable to high N.A. (N.A. > 1) objective lens immersed in oil. A more
accurate expression is as follows:
qffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffi
λ
ω0 = n2oil − NA2 (8:6)
π*NA
sffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffi
 
λz 2
ωð z Þ = ω 0 1 + (8:7)
πω20

where noil is the refractive index of immersion oil. And, it can also be an identical
quantity, as follows:
sffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffi
 
λ z2 2
ωð z Þ ≡ zR + 2 (8:8)
nπ zR

where, zR is the Rayleigh length, as follows:

πω20
zR = (8:9)
λ
When I reaches the threshold intensity Ith for initiating polymerization, that is,
I(r,z) = Ith, combining eqs. (8.2), (8.6)–(8.9), the diameter D and the length L which
are relative can be shown as follows:
sffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffi
 
I0
D = ω0 ln (8:10)
Ith
256 Xuewen Wang et al.

sffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffi
  ffi
I0
L = 2zR −1 (8:11)
Ith

If the photopolymerization is dependent on the intensity as I ∝ IthN, and N is the

order of nonlinear absorption, the D and L in nonlinear condition are as follows:
sffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffi
  ffi
I0 1
D = ω0 ln * (8:12)
Ith N
sffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffi
 1
I0 N
L = 2zR −1 (8:13)
Ith

The intensity of threshold (C) is relative to the primary initiator particle density (ρ0)
and threshold initiator density (ρth), as follows:
 
ρo
C = ln (8:14)
ρ0 − ρth

As we know, the voxel radius is proportional to I(r) during linear absorption, and
proportional to I2(r) during TPA process. Thus, after normalization, the relationship
between I(r) and r is shown in Figure 8.4.

Single-photon
absorption
Intensity (a.u)

Threshold

Two-photon
absorption

–750 –500 –250 0 250 500 750

Wavenumbers (nm)

Figure 8.4: The diagram of spot radius for single-photon (yellow) and two-photon (blue)
absorption.
 Chapter 8 Functional 3D nanoprinting via femtosecond laser nonlinear lithography 257

The violet and blue (three types of color depths) curves represent the single-
photon absorption and two-photon absorption process, respectively. The different
depths mean different nonlinear absorption curves under laser intensity changes.
The red line indicates that when the light intensity changes, the diameter correspond-
ing to the full width at half maximum (FWHM) is a fixed value, which is determined
only by the focusing condition, N.A., and laser wavelength [32]. The length of the in-
tersection of the threshold (indicated by the gray line) and the curve is the diameter
of the voxel. It will change with variation in the laser intensity.
In summary, we can change the radical density (adjusting different contents of
photoinitiators) to change the threshold. And we are also able to adjust the laser
intensity, scanning speed, laser power and exposure time to control the resolution,
when fabricating [33].
After years of development, the resolution of TPL has improved well. Many
groups have contributed a lot on improving the resolution, including changing the
process parameters, adding radical quencher, mixing photoinitiators or other addi-
tives and using STED-like lithography.
From the earlier discussion, we can confirm that the main process parameters
are laser power, exposure time and the N.A. of the objective. They can easily and
effectively affect the result of resolution in fabrication. Thus, more efforts on tuning
these parameters were taken in order to improve the fabrication accuracy.
In 2001, Kawata et al. [34] first used TPL to fabricate microdevices with feature
size close to the diffraction limit. A 3D microstructure with spatial resolution of 120
nm was first reported. The bull sculpture (Figure 8.5(a)) produced by laser scanning
in sub-micro scale led to the development of TPL over the next several decades.
In order to control the exposure time, switching the shutter and adjusting the
scanning speed are direct methods that are widely used in pinpoint scanning mode
(PSM) and continuing scanning mode (CSM), respectively. Because of the lower me-
chanical response of the shutter, PSM needs more exposure time, which results in
lower resolution. However, in CSM, the scanning speed can be easily changed to
get a higher resolution. Tan’s group [33] explored the effect of laser scanning speed
on line width through experiments (Figure 8.5(b)). They fabricated a fiber with fea-
ture size of sub-25 nm at a laser power of 20 mW and scanning speed up to 700 um/s.
In The next year, Dong et al. [21] improved lateral spatial resolution to 20 nm by
changing the exposure time. Besides, the AR, which is critical for fine 3D micro/nano-
devices fabrication was also reduced to 1.38.
Wang et al. [35] demonstrated a new strategy to fabricate suspended nanonet-
works with feature size below 10 nm and nearly 7 nm in width, taking advantage of
nonlinear lithography. In this work, they focused on exploiting initial stages of
cross-linking in the photoresist (IP-Dip, Nanoscribe Gmbh) (Figure 8.5(c)). They in-
vestigated a method to increase resolution up to several nanometers by research for
sub-threshold conditions. The supporting walls were fabricated first, which leads
258 Xuewen Wang et al.

Figure 8.5: (a) Bull sculpture produced by raster scanning. Reproduced with permission from [34].
Copyright 2001 Springer Nature BV. (b) The relationship between the feature size of the suspended
fibers and architectures. Reproduced with permission from [33]. Copyright 2007 American Institute of
Physics. (c) Schematic and fabricated results from different cross-linking process. (i) – (ii) Random
nucleation cross-linkers are distributed homogeneously. (iii) – (iv) Regular cross-linking: laser
exposure well above the threshold results in cross-linkers distributed in high concentrations.
(d) Schematic of 3D wall structure and Scanning electronic microscopy (SEM) images of the
narrowest nanoweb with 7 nm feature size. Reproduced with permission from [35]. Copyright 2018
IOP Publishing Ltd.

the cross-linkers to distribute homogeneously; then, sub-threshold exposures were

used to the produce nanolines (Figure 8.5(d)).
The theoretical issue of TPP has discussed earlier. As for quenching process, it is
expressed in eqs. (8.15)–(8.17) which is different from TPP process [36]. The photoini-
tiators (PI) absorb photons from TPA chromophores to the excited state (PI*) and de-
compose to produced radicals (R·) at the same time. Radical quenchers (Q) replace the
monomers (M) to combine with radials and then produce quenched radicals. Lastly,
the RQ· can be deactivated by release of heat or irradiation. Thus, radical quenchers
 Chapter 8 Functional 3D nanoprinting via femtosecond laser nonlinear lithography 259

can inhibit monomer polymerization to a certain extent, in order to enhance the reso-
lution of photocured product.

PI ! PI* ! R · + R · (8:15)

R · + Q ! RQ · (8:16)

RQ · ! RQ + heat or hν (8:17)

Figure 8.6 shows the schematic diagram of radical quenching process [36]. The radi-
cal quencher is evenly dispersed inside the photoresist. As we mentioned earlier, the
intensity of laser beam approximately has a Gaussian distribution, which determines
the density of radicals. At the center of the focus area, higher light intensity results in
higher radical density enough to diminish or avoid the quenching effect. But as
the distance goes away from the focus, the density of radical decreases, so that the
quencher can terminate the early polymerization reaction and chain growth.

Figure 8.6: Schematic of the mechanism of radical quenching. Reproduced with permission from [36].
Copyright 2003 Springer Nature BV.

In 2005, Takada et al. intentionally added radical quenchers into photoresist in

which the concentrations of the additive initiator and quencher were 0% and 0.8%,
respectively [37]. The next year, S. H. Park et al. similarly proposed a method using
2,6-di-tert-butyl-4-methylphenol (DBMP) as a radical quencher to increase the reso-
lution up to 100 nm, and experimentally investigated the relationship between the
quenching effect and the amount of radical quencher [36]. Besides, comparing the
strength of the contents of radical quencher with the original resin, they pointed
out that the quenching effect would reduce the mechanical strength of polymerized
structures because of their short chain lengths.
From the previous content, it can be known that the feature size is also related
to the polymerization threshold, in addition to the exposure time and laser power.
260 Xuewen Wang et al.

According to eq. (8.14), the photoinitiator is one of the keys to determine the threshold
[16, 38]. In 1999, Perry and Marder firstly put forward a series of rules for choosing
photoinitiators [16]: (i) Chromophore with a large two-photon absorption cross-section
(δTPA), such as D-π-D structure. When a laser beam passes through a nonlinear me-
dium, the photoresist will absorb photons to excite the system, which will cause
the attenuation of the laser beam. δTPA refers to the probability that the incident
photon is captured by the target substance. (ii) High initiation efficiency. In order
to initiate photopolymerization with high efficiency, a photoinitiator that can poly-
merize monomers with a shorter exposure time can be carefully selected, resulting
in a higher resolution. (iii) A mechanism that can activate chemical functions through
chromophores, such as charge transfer. In short, highly sensitive and efficient photo-
initiators lead to a lower threshold, in order to increase the resolution effectively.
More details on the progress of the newly developed two-photon initiators are pre-
sented in Chapter 2.
Xing et al. [38] prepared a photoresist mixing 9,10-bispentyloxy-2,7-bis[2-(4-
dimethylamino-phenyl)-vinyl] (BPDPA, a highly sensitive and efficient photoinitiator)
(Figure 8.7(a)), and dipentaerythritol hexaacrylate (DEP, cross-linker, providing
amounts of polymerizable double bounds (Figure 8.7(a)). The components successfully
improve lateral spatial resolution up to 80 nm (Figure 8.7(b)), under a laser power
of 0.8 mW and a linear scanning speed of 50 μm/s.
In addition to selecting different photoinitiators, scholars have been trying to
add other additives to the photoresist to obtain specific properties. Peng et al. [39]
proved that the presence of Quantum dots (QDs) can increase the lateral resolution,
and they produced polymer lines that reached 75 nm (Figure 8.7(c, d)). The mecha-
nism is that the QDs absorbed photons during writing, leading to lesser photons
being absorbed by the photoinitiators.
Stimulated emission depletion microscopy (STED) proposed by Stefan W. Hell
in 1994 has been continuously developed over recent years, providing a lot of help
for the observation and analysis of microstructures in the fields of biomedicine and
materials. Inspired by this, scholars applied STED to TPP-based nonlinear lithogra-
phy, which significantly improved the resolution of fabricated architectures [30].
Photon-induced mechanism that locally prohibits the formation of insoluble cross-
linked polymers is suitable. There are several types of STED-like lithography according
to the depletion mechanisms, as shown in Figure 8.8 [40–42]: (i) STED lithography. PI
molecules are initiated to S1 during TPA process, and then are returned back to the
ground state (S0) through stimulated emission (SE) in STED lithography. At the same
time, a part of the PIs proceeds to the triplet (T1) via intersystem crossing (ISC) and
generates R · to cross-link polymers (Figure 8.8(a)); (ii) Resolution Augmentation
through Photo-Induced Deactivation (RAPID). In this process, an intermediate state
will result after TPA, but upon light excitation, the intermediate state loses its activity
and cannot cross-link the polymers (Figure 8.8(b)); (iii) Two-color photoinitiation/in-
hibition (2PII) lithography. PI molecules are excited by one of the photons through
 Chapter 8 Functional 3D nanoprinting via femtosecond laser nonlinear lithography

Figure 8.7: (a) Molecular structure of photoinitiator and cross-linker. (b) SEM images of photopolymeric lines with feature size of 80 nm. Reproduced
with permission from [38]. Copyright 2007 American Institute of Physics. (c) SEM images of polymer limes adding QDs with features size of 75 nm
(d) Photoluminescence images of QDs-containing 3D truss lattice showing emission at 460 nm.
261
 (a) STED lithography
(b) RAPID lithography
262

S1* Non-radiative decay

Sn or non-initiating product
S1 ISC
S1

SE

TPA
T1 R. RM. Cross-linked

TPA
polymer Cross-linked
S0* Intermediate
polymer
S0* state
S0
S0
(c) 2PII lithography (photoinhibitor)
(d) Excited-state absorption + Non-radiative decay
Sn
Xuewen Wang et al.

R. RM. Sn
Cross-linked
polymer S1* Tn

Initiator
S0
Scavenging Termination S1 ISC

Wiley‐VCH Verlag GmbH and. KGaA Weinheim.

Sn

TPA
Q. T1
R. Cross-linked
RM.
polymer
S0*

Initiator
S0
S0
(e) Excited-state absorption + Resist heating
Sn
Tn
S1*
ISC
S 1
T1

TPA
S0*
S0

(a) STED lithography. (b) RAPID lithography. (c) 2PII lithography. Excited-state absorption and
Figure 8.8: Several transitions for the different depletion mechanisms in STED-like lithography.

(d)nonradiative decay; (e) resist heating. Reproduced with permission from [40]. Copyright 2014
 Chapter 8 Functional 3D nanoprinting via femtosecond laser nonlinear lithography 263

one-photon absorption (OPA) to generate radicals(R ·), which can initiate the polymer-
ization. But another photon plays an opposite role in generating noninitiating radicals
(Q ·), which limits the degree of polymer cross-linking (Figure 8.8(c)). (iv) In excited-
state absorption, after excitation, the depletion light can be absorbed by several inter-
mediate states. From such highly excited states, the polymerization reaction occurs
after the nonradiative decay to the ground state (Figure 8.8(d)). (v) During resist heat-
ing, it can be heated by repeated absorption from the excited state and by nonradia-
tive attenuation to the same state. As the temperature rises, the properties of several
resists will change and inhibit excitation, initiation or polymerization (Figure 8.8(e)).
Utilizing spatial phase-shaping, Linjie Li et al. fabricated nanolines with scalable
resolution of the deactivation down to 40 nm feature sizes [12]. The laser emitted two
light beams to play different roles. By using visible light for TPP-DLW (780 nm) and
STED 352 nm as shown in Figure 8.9, Richard Wollhofen and his group used a mixed
of tri- and tetra-acrylates and 7-Diethylamino-3-thenoylcoumarin as photostarter to
produce a structure with lateral sizes of 55 nm [43]. They proved that the resolution
could be controlled by the components of photoresist, the position of the focal spot,
the scanning speed and the power of the STED and femtosecond laser.

Figure 8.9: Setup for STED lithography. Reproduced with permission from [43]. Copyright 2013
Optical Society of America.

Figure 8.10 summarizes the development of resolution through TPP in the past
20 years. Scholars constantly seek new ways to improve resolution. Although the
resolution continues to increase over time, it is limited to several nanometers. On
the one hand, there are certain bottlenecks in the development of resolution. On
the other hand, when the resolution reached a certain level, scholars began to turn
to functional applications and manufacturing speed gradually.
264 Xuewen Wang et al.

Changing process parameters

120 Adding radical quencher
Mixing photoinitiators and additives
Combining STED-like lithography
100
Resolution (or feature size) (nm)

80

60

40

20

0
2000 2005 2010 2015 2020
Year

Figure 8.10: Improvement of resolution through 2 PPM with different methods.

8.3.3 Making 3D micro/nanoprinting faster

Ultrafast laser for TPL is a powerful device for fabricating 3D micro/nanostructures. How-
ever, the printing efficiency is always a critical problem in inhibiting the development of
TPL in industrial manufacturing. In order to deal with this problem, many scholars have
explored several methods and devices to increase the efficiency such as multiple-beam
interferometry method, multifocus parallel processing and space-time focusing tech-
nique. Hence, it has realized cross-scale micro/nano processing and manufacturing from
nanometer to centimeter size, making it useful in a variety of functional fields [44].
The relative speed between focal spot and sample contributes to printing effi-
ciency directly. In order to realize the manufacturing at the 3D scale, the sample
stage usually moves in the lateral axis (x-y), and the objective moves in the axial
axis (z), which results in the focal spot moving in any direction. Besides, the galvo-
scanners can also be rotated to tilt the wavefront of the laser beam, which results in
the focal spot moving accurately (Figure 8.11). Notably, aberrations and vignetting
can easily lead to displacement and distortion of the focal intensity distribution.
In the previous section, we detailed the relationships between the processing size
and each parameter, the printing speed is in inverse proportion to the exposure time.
Recently, many scholars have proposed several works to improve printing speed, while
ensuring the resolution. In 2014, Hayaski et al. used a pair of spatial light modulators
 Chapter 8 Functional 3D nanoprinting via femtosecond laser nonlinear lithography 265

Resist

Substrate

Displaced
focal spot Objective

Tip Tilt

Structuring
beam

Figure 8.11: Schematic of galvanometric mirror moving in printing. Reproduced with permission
from [1]. Copyright 2015 John Wiley and Sons Books.

to perform arbitrary and variable beam shaping of femtosecond lasers and demon-
strated vector wave femtosecond laser processing, based on wavefront and polariza-
tion holographic processing [45]. This method provides a guidance to fabricate
periodic complex nanostructures rapidly and achieve high-speed imaging via fem-
tosecond laser, but unfortunately, the researchers did not show the resolution and
printing speed accurately in detail. In 2015, taking advantage of a spatial light mod-
ulator, Yang et al. loaded computer-generated holograms (CGHs) into it, so that the
beam was pre-modulated into multiple foci to achieve multifocus spots parallel proc-
essing (Figure 8.12(a)) [46]. With multiple foci, the processing time could be reduced
greatly, because of the decrease of numbers of repeated 3D scanning in fabricating
such spiral photonic structures. It took only 6 m to fabricate one microlens, but 20 m
in the conventional single laser spot fabrication. Similarly, Abid and his group suc-
cessfully printed large-area complex structures with cascade resolution and 3D pro-
file, by using multiple exposure of two-beam laser interference with angle variation
and period modulation [47]. Through experimental testing, they proved that the struc-
ture processed could simulate a variety of supernatural phenomena, such as super
hydrophobicity, iridescence, directionality of reflectivity and polarization at different
colors. In 2019, Wang et al. achieved fabrication efficiency up to 0.18 mm3/s (8200
voxels/s), when the scanning speed and layer spacing were 40 mm/s and 50 μm, re-
spectively, by combing a 2D scanning galvanometer with a 2D mobile platform [48].
This motion system could lead focal spot to move to any displacement accurately, to
complete 3D additive manufacturing (Figure 8.12(b)). This design would achieve high
printing speed and large printing area, which could further improve printing effi-
ciency in the future. In fact, the serial point-by-point printing set up of nonlinear li-
thography is too slow for many applications. Parallelization technology does not have
266 Xuewen Wang et al.

Figure 8.12: (a) Schematic experimental illustration of the multiple beams by the spatial light
modulator, and SEM image of fabricated “L” structure. Reproduced with permission from [46].
Copyright 2015 Elsevier Science and Technology Journals. (b) Schematic experimental illustration
of the rapid printing and SEM images of printed sculpture of Albert Einstein’s head and Confucius
in fused silica. Reproduced with permission from [48]. Copyright 2019 MDPI.

sub-micro resolution and cannot fabricate complex architectures. In the same year,
Saha et al. realized the hierarchical parallel manufacturing based on projection by
spatially and temporally focusing an ultrafast laser, which effectively solved this prob-
lem [49]. This technology has advantages that are three orders of magnitude above
the existing serial technology in terms of resolution, while ensuring high manufactur-
ing rates [49].

8.4 Photoresist
In addictive manufacturing, fs-DLW uses negative photoresist a lot, hoping to be able
to manufacture finely controllable structures in designated areas. In general, there are
 Chapter 8 Functional 3D nanoprinting via femtosecond laser nonlinear lithography 267

two basic components of photoresist: (i) monomers or a mixture of monomers and

oligomers, which are the basic ingredients of forming polymers. (ii) a photoinitiator,
which will absorb photons produced by laser beam and generate the active radicals to
initiate polymerization [50]. They mainly include organic materials, SU-8, photosensi-
tive hybrid materials, hydrogels, natural polymers and proteins. Their improvement
determines the development and application of TPP-based nonlinear lithography to a
certain extent.

8.4.1 Organic polymers

Over a century of development, use of organic polymers has expanded from high-
tech devices to people’s daily necessities. With external stimulants, monomeric
units are induced to form large polymer networks. After absorbing photons, photo-
polymerization is represented as chain growth and synthesis of polymers. As one of
the earliest photoresists, organic polymer comprises simple raw materials and can
be obtained through a single step. Most of these use acrylates as polymerization
monomers, and then are mixed with an appropriate amount of photoinitiators.
In 1997, Maruo et al. mixed photoinitiators, urethane acrylate monomers/oligomers
to generate a photoresist in order to fabricate a spiral microstructure [51]. This was the
first time that scholars used acrylate monomers in DLW-based addictive manufactur-
ing. Taking advantage of low cost and easy availability, this type of material has been
widely applied into photopolymerization. In 2008, Tayalia et al. mixed SCR368 with
SR400 in the ratio 48:49, adding 3% of photoinitiators as two-monomer composition
resin for manufacturing (Figure 8.13(a)) [52]. It is a pioneering work that can provide
precise and independent control of architectural parameters as a model 3D extracellu-
lar matrix to research on cell adhesion and migration. Later, Weib et al. found that
three different types of methacrylate photopolymerizable monomers (methacrylated
oligolactones, urethane dimethacrylate and poly(ethylene glycol diacrylate)) could be
used as a highly efficient photoresist and relied on fs-DLW to fabricate them into geo-
metric structures at different scales and sizes (Figure 8.13(b)) [53]. As technology con-
tinues to mature, more and more complex structures are manufactured with a high
resolution (Figure 8.13(c, d)) [54].
SU-8 plays an important role in organic polymer photoresists. It is an epoxy-
based negative photoresist that has been widely used in additive manufacturing [55].
Figure 8.14 shows a single chemical structure of an SU-8 molecule [56]. It can be seen
that the epoxy group is bound by aromatic hydrocarbon. Thus, as opposed to normal
organic photopolymers, the principle of polymerization is a cationic ring-opening
process, which leads to the cyclic compound monomer being converted into a linear
polymer through the ring-opening addition [57]. Benefitting from this, SU-8 has
cross-linked networks with a high degree after polymerization. As a result, it has
excellent chemical resistance, high temperature resistance and high dimensional
268 Xuewen Wang et al.

Figure 8.13: SEM images of (a) a scaffold; (b) 2PP-derived scaffolds. Reproduced with permission
from [52, 53]. Copyright 2018 and 2011 Elsevier Science and Technology Journals. SEM images of
(c) A logo sized 280 μm × 280 μm with feature size of (d) 200 nm. Reproduced with permission from
[54]. Copyright 2017 Elsevier Science and Technology Journals. Scale bars are 25 μm for (a),
400 μm for (b), 25 μm for (c) and 4 μm for (d).

stability. Besides, it also has a high sensitivity to other photoresists, because of

the high functionality of the epoxy group, so that it has been applied in various
lithography technologies.
Since two-photon polymerization of SU-8 came out in 1998, scholars have ap-
plied it into a lot of researches. In the past few years, many groups have found that
it is suitable for fabrication of microfluidics constructs, micro electromechanical
systems and bio-applications [58]. Taking advantage of the flexibility of nonlinear
lithography, SU-8 was fabricated into a complex suspended microchannel resonator
[59]. In another field, SU-8 was used to design burr-like spherical micro-biorobot to
carry and deliver targeted cells [60].
 Chapter 8 Functional 3D nanoprinting via femtosecond laser nonlinear lithography 269

O CH2 O CH2 O CH2 O CH2

CH CH CH CH
H2C H 2C H2C H 2C

O O O O

H2 H2 H2
C C C

H 3C C CH3 H3C C CH3 H3C C CH3 H3C C CH3

O O O O

H 2C H2C H 2C H 2C
CH CH CH CH

O CH2 O CH2 O CH2 O CH2

Figure 8.14: Chemical structure of SU-8.

8.4.2 Hybrid photosensitive resin

With the development of TPL technology, scholars no longer want to limit it to high
resolution in fabrication, but would like to create a variety of functional materials
in 3D. However, there is a limit to selecting proper materials for AM at the micro/
nanoscale, which is especially pronounced for optical, magnetic and piezoelectric
properties. Thus, scholars have paid attention to the improvement of hybrid compo-
sites [61].
As a commercial silicon-based photoresist, ORMOCER is the most widely used
and studied material due to its hardness, chemical and thermal stability. It contains
highly cross-linked organic networks as well as inorganic components and has
been used in photonic applications. Its performance surpasses those of inorganic or
polymeric materials [62].
Besides, scholars used metal-containing acrylic-based materials as polymeriza-
tion monomers to synthesize organic-inorganic photoresist, in order to obtain spe-
cific properties. In essence, it still uses photopolymerization of organic components
to form the framework, but will perform the properties of ceramics after pyrolysis. It
provides a new way to effectively solve the problem that ceramics are difficult to
270 Xuewen Wang et al.

Figure 8.15: (a) The voxel height is relative to the average laser power and Zr content in the
photoresist. (b) SEM images of fabricated photonic crystal structures and the linear relation in
refractive index of the material with different molar ratio. Reproduced with permission from [64].
Copyright 2008 American Chemical Society. (c) SEM images of the changes of woodpile structures
after pyrolysis. (d) EDS spectrums shows only TiO2 remain after pyrolysis. Reproduced with
permission from [66]. Copyright 2020 American Chemical Society.
 Chapter 8 Functional 3D nanoprinting via femtosecond laser nonlinear lithography 271

fabricate in complex structures at the nanoscale [63]. As a typical example, Ovsiani-

kov et al. combined Zirconium n-propoxide with methacrylic acid to synthesize the
Zr-containing acrylic photoresist, taking full advantage of the sol-gel organic-
inorganic hybrid technology [64]. During fabrication, these materials were similar
to organic polymers, and the resolution was not only controlled by the laser power
but also affected by the components’ molar ratio (Figure 8.15(a)). As a result, the
refractive index of the prepared structure to light after pyrolysis could be modified
by varying the molar ratio (Figure 8.15(b)). Similarly, Greer et al. added acrylic acid
to titanium(IV) ethoxide to obtain a titania photoresist [65, 66]. After pyrolysis
shrinking, the architecture could be transformed from polymer to ceramic, in which
the carbon component in the form of carbon dioxide was completely eliminated
(Figure 8.15(c, d)). Benefitting from the controlled architecture in sub-micro scale of
ceramics, the titania photoresist was manufactured into cubic and truss for solar
water purification [65] and 3D dielectric photonic crystals [66], respectively.
To some extent, we are able to fabricate any complex ceramics in different ele-
ments by varying the hybrid of metal-based ethoxide. Till now, scholars have pro-
posed a series of functional oxides photoresist (Al2O3, HfO2, TiO2, ZrO2, Ta2O5 and
Nb2O5), which could be applied in various fields by controlling structures and resolu-
tion after shrinkage [67]. The emergence of this type of organic-inorganic photoresist
preparation technology has greatly expanded the application range of nonlinear
lithography.

8.4.3 Hydrogels

Hydrogels are a type of extremely hydrophilic gel with 3D cross-linked network

structure. They swell rapidly in water and maintain a large volume of water, with-
out dissolving in the swelling state. The cross-linked network leads to swell and
hold a large volume of water, and the degree of cross-linking determines the
amount of water absorption [68]. A higher degree of crosslinking results in lower
water absorption.
Due to the presence of hydrophilic groups (such as -NH2, -COOH, -OH, -CONH2,
-CONH and -SO3H), hydrogel monomers should exhibit sufficient water solubility
and biocompatibility that resembles the extra-cellular matrix from the view of biol-
ogy[69]. For a long time in the past, natural and synthetic polymers have been used
as raw materials for hydrogels, and then modified natural polymers have been de-
rived. Naturally, most kinds of hydrogels can be broadly divided into three categories:
(i) natural polymers and proteins, (ii) synthetic hydrogels and (iii) modified natural hy-
drogels [70]. They are widely applied in cell engineering, tissue engineering and drug
delivery. Natural hydrogels occupy a decisive position in simulating native extracellu-
lar matrix due to their good biocompatibility, low toxicity and easy degradability [69].
There are several kinds of organic polymers that can be used as raw materials for
 272
Xuewen Wang et al.

Figure 8.16: (a) SEM images of dynamic caging and culture for living cells. Reproduced with permission from [71]. Copyright 2018American Chemical
Society. (b) Schematic for fabricating microrobots. Reproduced with permission from [72]. Copyright 2019 John Wiley and Sons Books. (c) Schematic
of swelling process in the air and in the water. Reproduced with permission from [73]. Copyright 2018 Elsevier Science and Technology Journals.
 Chapter 8 Functional 3D nanoprinting via femtosecond laser nonlinear lithography 273

synthetic hydrogels, such as PEGDA (the most popular), GELMA and MMP2. It is possi-
ble to fine-tune specific mechanical properties during manufacturing, because the
component ratio can be precisely adjusted. Modified hydrogels are chemically modi-
fied in the laboratory to improve or adjust specific properties of natural hydrogels.
The hydrogels mentioned here, along with their material properties, have been
widely investigated for various bio-applications [69]. Pennacchio et al. combined
acrylamide-modified gelatin B with azo cross-linker and Irgacure 369 to synthesis a
kind of modified photoresist, which could be fabricated into a “dynamic” caging as
cell niches (Figure 8.16(a)) [71]. One of the advantages of TPL is that we can add
various components into photoresist. For example, the magnetically actuated and
degradable 3D helical microrobots were fabricated by adding PETA which contains
magnetic Fe3O4 nano particles(NPs) and 5-FU (Figure 8.16(b, c)) into PEGDA [72].
Using the water-absorption properties of PEG-based hydrogels to advantage, Lv
et al. created a humidity-response microstructure that was able to expand when hu-
midity changed (Figure 8.16(d)) [73].

8.4.4 Summary of photoresist development

Table 8.1 shows several types of photoresists and their properties. It can be clearly
seen that the development of photoresist has gone through a long process. Organic
polymers are the earliest photoresists used in TPL, and they are also the most com-
plete system, at present, that have mature commercial products (such as SU-8, SCR-
500 etc). The emergence of hybrid photosensitive materials fully demonstrates the
wide range of applications of this technology, which provide a new idea in fabricat-
ing ceramic in complex and sub-micrometers structures. As for hydrogels, since it
mainly based on PEG and other biocompatible gelatins as raw materials, it has
been getting a lot of attention to the biological field. The development of photore-
sists is aimed to continuously improve and enhance the properties that attract vari-
ous applications and will be discussed in the next section.

8.5 Applications of functional 3D nanoprinting

In the past decades, photoresists and TPL have made great development in enriching
types of raw materials and achieving small feature sizes [11, 95]. While much progress
has been made in expanding functional applications through the years, by printing
precise and complex structures, one can confer the various structures with specific
properties to adapt to peculiar and novel environment. The reason why this technol-
ogy can be applied into many fields is also based on its unparalleled advantages.
Table 8.1: Various photoresists and their properties.
274

Category Raw materials Structure Application Properties Reference year

Organic SCR- Spiral Process It is the earliest method proposed for D [] 
polymer structure optimization microfabrication with PP.
SR-; SR- D scaffold Cell engineering It has precise and independent control of architectural [] 
parameters to determine cell adhesion and migration.
UDMA;DLMA D scaffold Biointerfaces Provided a new idea for cell to be cultured in vitro close [] 
to natural conditions.
Xuewen Wang et al.

Acrylate resign Woodpile Cell migration Controllable of pore size and topology was prepared. [] 
SU- D scaffold / SU- was used in PP, first. [] 
SU- D scaffold Process Fabricated in various micro/nanostructures rapidly. [] 
optimization
SU- Shell Resonator The single step fabricated suspended microchannel [] 
resonator.
SU- Microrobot Cell engineering High magnetic field drove ability and cell viability. [] 
Hybrid Titanium ethoxide;SCR- Woodpile PhCs It was a method for combining Ti+ with urethane [] 
photosensitive  acrylate resigns to obtain complex ceramics.
Zirconium propoxide Woodpile PhCs; ceramics It referred the relationship between refractive index of [] 
(ZPO); methacrylic acid structures and ZPO content.
(MAA)
Titanium ethoxide; Bulk Tissue A fabricated cubic nanostructure was applied in solar [] 
acrylic acid(AA) engineering water purification.
Titanium ethoxide; AA Woodpile PhCs; ceramics The as-fabricated materials were dense and [] 
homogeneous after pyrolysis.
Hydrogels PEtOx-DA D scaffold Process Improved accuracy and speed in manufacturing. [] 
(synthesis) optimization
PEG; FeO D scaffold Magnetic A magnetically actuated D hydrogel microstructure was [] 
sensors fabricated with size up to  μm.
 PEGDA Microrobots Drug delivery Superparamagnetic hydrogels composites were [] 
fabricated to microdevices whose framework was
biodegradable.
PEGDA Microcavity Tissue Responded to change in humidity. [] 
engineering
PEGDA Flower-shaped Tissue Improved reproducibility and endurance for humidity [] 
engineering response.
PEGDA Pyramid-like; Tissue It was suitable for PH sensing in soft biological tissues. [] 
Dome-like engineering
PEGDA;PETA;FeO;-FU Microrobot Drug delivery It achieved controllability of drug delivery release and [] 
hyperthermia therapy.
PEG D scaffold Cell engineering Selectivity immobilized a particular cell by cross-linking. [] 
Methacrylate gelatin Woodpiles Cell engineering Promoted cell adhesion, migration and toxicity [] 
(GELMA) reduction.
Methacrylate gelatin Microswimmer Drug delivery It showed nontoxicity and high values of forward [] 
(GELMA) velocity.
Matrix metalloproteinase Microswimmer Drug delivery It represented magnetic driving and controlled enzymatic [] 
degrade response to the markers.
Hydrogels Bovine serum album D free-form Process Cross-linked various proteins in fabrication. [] 
(natural) (BSA) optimization
Hyaluronic acid (HA) D scaffold Cell-engineering Provided simultaneous topographical and chemical cues [] 
to cells.
BSA D scaffold Process Improved fabrication efficiency. [] 
optimization
BSA D scaffold Process Specified the relationship between parameters and [] 
optimization feature size.
Hydrogels HA-modified Tissue
Chapter 8 Functional 3D nanoprinting via femtosecond laser nonlinear lithography

D scaffold The PP feasibility was proved with a low writing speed. [] 
(modified) engineering

(continued )
275
Table 8.1 (continued )
276

Category Raw materials Structure Application Properties Reference year

Methacrylamide- D scaffold Tissue The scaffold had excellent stability in culture medium. [] 
modified gelation engineering
(GELMOD); HA
BSA-modified D scaffold Tissue It showed superior cytocompatibility. [] 
engineering
Hyaluronic acid − D scaffold Process Different degrees of cross-linking induced different [] 
tyramine optimization swelling shrinking.
Xuewen Wang et al.

Acrylamide-modified D scaffold Cell engineering Photoactuable cell confining system [] 
gelatin
 Chapter 8 Functional 3D nanoprinting via femtosecond laser nonlinear lithography 277

At present, it is widely applied in the fields of mechanical metamaterials, MEMS, elec-

tronic, biomedicine, etc. This section mainly discusses their valuable functionalized
devices in various fields.

8.5.1 Micromechanics

Mechanical metamaterials refer to a kind of man-made materials with special me-

chanical properties (such as Young’s modulus enhancement, pressure twist response,
negative Poisson ratio, etc.), whose characteristics come from their precise structural
design [96]. TPL has recently opened the doors to build complex mechanical metama-
terial architectures in the micro/nanoscale, which were previously inaccessible. It is
a prominent tool for the preparation of metamaterials in the microscopic field [97].
The progress of metamaterials development, like most other fields, is from theory
to practice. As a manufacturing technology, TPL was first combined with metamateri-
als only to show that such structures could be manufactured, and the performance
analysis mostly relies on the finite element simulation rather than actual manufactur-
ing with mechanical test. Kadic et al. designed pentamode mechanical metamaterials
based on the diamond model [96]. By adjusting the structural parameters, they found
that the ratio of bulk modulus to shear modulus can reach 1000 (Figure 8.17(a)), via
the finite element simulation (named COMSOL Multiphysics). Unfortunately, They
only fabricated such a structure through TPL, but did not carry out more in-depth
analysis and application expansion. In the case of this system, Buckmann et al., from
the same group, fabricated the same polymer microstructures and conducted elasto-
mechanical measurements that were applied in elasto-mechanical unfeelability cloaks
(Figure 8.17(b)) [98]. They demonstrated that it was difficult to find the rigid cell cover-
ing a cloak with additional pentamode-metamaterials.
With the development of TPL and mechanical test at the nanoscale, scholars
have combined simulation with fabrication to verify the performance of microstruc-
ture mechanical metamaterials. In 2017, Frenzel et al. designed a chiral structure that
could perform twists when an axial stress was applied [99]. Furthermore, they fabri-
cated polymer samples to prove for twists properly. Portela et al. also combined fabri-
cation with analysis to explore the impact of node geometry on the effective stiffness
of 3D micro metamaterials structure (Figure 8.17(c)) [100]. In their study, the authors
selected several specific parameters to fabricate and analyze to verify the correction
of simulation. Dejean et al. reported a 3D nano-plate lattice structure which exhibit
optimal isotropic stiffness (Figure 8.17(d)) [101]. Latter, Crook et al. followed similar
approach to prepare this structure and made a compression experiments of various
parameters with different relative densities (Figure 8.17(e)) [102]. Deeply, they proved
that Young’s modulus and strength are relevant to the structural relative density
(Figure 8.17(f)).
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Xuewen Wang et al.

Figure 8.17: (a) Finite element simulation of pentamode with different structural parameters. Reproduced with permission from [96].
Copyright 2012 American Institute of Physics. (b) A mode of unfeelability cloak. Reproduced with permission from [98]. Copyright 2014
Springer Nature. (c) Relative Young’s modulus testing with different nodes combing simulation and fabrication. Reproduced with
permission from [100]. Copyright 2018 Elsevier Science and Technology Journals. (d) Measured Young’s moduli for different types of
plate lattices. Reproduced with permission from [101]. Copyright 2018 John Wiley and Sons. (e) Young’s modulus of cubic + octet plate-
nanolattices with different relative density. (f) Compression experiments of pyrolytic carbon cubic + octet plate-nanolattices.
Reproduced with permission from [102]. Copyright 2020 Springer Nature.
 Chapter 8 Functional 3D nanoprinting via femtosecond laser nonlinear lithography 279

Actually, the current application of TPL in metamaterials is to combine the fi-

nite element simulation with nonlinear lithography. It is a trend to use simulation
software to systematically analyze various structural parameters of metamaterials,
and then select feature parameters for microstructure manufacturing to verify the
correctness of the simulation results. Of course, as a powerful tool for precise 3D
manufacturing at the micro/nanoscale, TPL has been investigated for such system
in order to achieve industry applications in the future.
It is important to find materials that can intrinsically generate movement under
stimulation, when we want to scale down machinery to the level of micro-electro-
mechanical system (MEMS). The critical points of using TPL to fabricate MEMS are:
(i) controlling the microstructure at the sub-micro scale (ii) manipulating the mo-
tion of the material under the influence of the external environment [103].
Here, we have given full play to the technical advantages of TPL based on two-
photon polymerization and use materials that respond to specific stimuli to form the
structure for mechanical motion [104]. Tian et al. fabricated methacrylate-based poly-
mer microwires that the polymer networks would expand or shrink when the interfa-
cial solvent polarity changed, and the responsive motion was reliable under repetition,
several times [104]. As mentioned earlier, Lv et al. made use of the hygroscopic swell-
ing properties of hydrogel to produce a humidity-responsive actuator (Figure 8.16(c))
[73]. Similarly, the microstructures that Scalper and coworkers designed, relying on
fs-DLW, could swell under the responsibility to PH [82]. Since these processes are dif-
fusion-controlled, the response will become slow and delayed. A type of temperature
and light respond soft microrobots were produced by Hippler et al.[105]. They demon-
strated that not only could the bending motion be controlled by changing the temper-
ature of the solution, but also a spatial controlled response by inducing a local
temperature increase under laser radiation (Figure 8.18(a)).
Besides, the properties of liquid crystals (LCs) have also been used in TPL. LCs
can flow like a liquid, but their molecules are aligned and ordered like a road (an-
isotropy) [106]. When energized, it is turned on and the array becomes orderly, al-
lowing light to pass; when it is not energized, the array is chaotic, preventing light
from passing. The LCs block or allow light to penetrate like a gate. In 2013, Zeng
et al. demonstrated that the molecular orientation of the polymer network could be
maintained when LCs phase microstructure was prepared [107]. Following previous
work, Descrovi et al. fabricated a light-responsive device using a photocurable azo-
polymeric compound [108]. When irradiated by a light source, the fabricated film
would show expansion process, then, would relax to the initial state as the irradia-
tion was switched off (Figure 8.17(b)).
Barbot et al. reported that they could fabricate a micropiston with maximum
dimension of 150 nm onto the top of 140-μm diameter capillaries, utilizing TPL tech-
nology [109]. When integrated with a microgripper, this actuator could grasp and
release microsphere (Figure 8.18(c)). It is a great progress in catheter actuation at
the sub-micro scale.
280 Xuewen Wang et al.

(a)
20 °C 45 °C Light off Light on

circulation circulation

10 μm 10 μm 20 μm 20 μm

(b) 60 60
6π
edge displacement
40 4π 40 2.5 μm
edge position
(laser off) edge position
20 20

y (μm)
2π (laser on)
y (μm)

0 0 0
–20 –2π –20

–40 Laser off –4π –40

Laser on
–60 –6π –60
–50 0 50 –50 0 50
x [μm] x [μm]
(c) Gripper Gripper
Piston
Piston

Glass
capillary 100 μm
50 μm 100 μm

Figure 8.18: (a) Bright-field optical micrographs of temperature-induced actuation and SEM images
of light-induced actuation. Reproduced with permission from [105]. Copyright 2019 Springer Nature.
(b) Unwrapped phase distributions of light transmitted under laser off/on showing membrane edges
motion. Reproduced with permission from [108]. Copyright 2018 Royal Society of Chemistry. (c) SEM
image of a micropiston integrated into a compliant gripper and demonstration of fetching a
microsphere.

8.5.2 Biomedical applications

Since TPL technology was originally generated for other fields, it requires interdisci-
plinary cooperation for biomedicine research. In practical applications, it is neces-
sary to make use of TPL to fabricate precise microstructures, but it also requires
special physical, chemical and biological environments to perform the intended
functions [110].
 Chapter 8 Functional 3D nanoprinting via femtosecond laser nonlinear lithography 281

In the previous section, we have introduced several photoresists that can be

used in the biomedical field. Here, we will focus on how these materials are applied
into biomedicine in combination with TPL.
In cell engineering, hydrogels are widely used in femtosecond nonlinear lithog-
raphy because of their better biocompatibility and lower toxicity, compared to
other photoresists, as shown in Table 8.1. In order to research on the relationship
between cell shape and function, hydrogels have been fabricated into a variety of
complex structures to fix cells or adsorb cells to induce migration.
Brigol et al. used hydrogels to prepare a 3D woodpile structure with a controlla-
ble degree of cross-linking and found that changes in the degree of cross-linking di-
rectly impact cell migration and adsorption efficiency (Figure 8.19(a)) [84]. Another
effective method is to connect the specific cells together through the cross-linking
network in the manufacturing process. The hydrogel line connecting cells can control
the flow and migration of cells [83]. This technology can be used not only to induce
migration, but also for cell fixation and shape control. Pennacchio et al. designed a
new “dynamic” caging culture system that could fix cells (Figure 8.16(a)) [71]. More-
over, they found that light irradiation would change the structure of the cage, so that
the shape of the cell could be modified. This research paves a new way to shape cells
in the engineered niches.
Mobile micro/nanorobots are one of the future biomedical research trends [111].
They are effective in controlling the directional movement of microstructures that
can deliver drugs to target cells. As we mentioned earlier in actuation applications,
one of the keys to drug delivery is to be able to generate a controllable driving
force, such as magnetic motive force. Other essential elements are biocompatibility
and biodegradability [110].
In 2016, Peters et al. fabricated a robotic device using superparamagnetic poly-
mer composite (Figure 8.19(c)) [80]. They added Fe3O4 into hydrogels to make the
device magnetic, in order to control motivation by adjusting the external magnetic
field (Figure 8.19(d)), and demonstrated that it could be naturally degraded into
nontoxic substances in the physiological environment. Later, a nontoxic photo-cross-
linkable hydrogel gelatinmethacryloyl (GelMA) was reported and has been fabricated
into biodegradable soft helical microswimmers via TPL [85]. Compared to rigid micro-
swimmers, it could keep high values of forward velocity when the step-out frequency
increased. With the deepening of research, scholars have become more accurate and
precise in drug delivery. In 2019, Park, with his coworkers, investigated that actively
controlled drug delivery, release and hyperthermia therapy could be enabled into mi-
crorobots with a 3D helical structure, through adding 5-fluorourcil(5-FU) [72]. In the
same year, Cevlan et al. demonstrated a 3D-printed biodegradable microswimmer,
which could also release other functional cargos to label specific cells, in addition to
delivery of drugs to the given microenvironment [86].
This type of biodegradable microrobot can be well applied in minimally invasive
surgery to reduce the patient’s treatment and recovery time as much as possible. In
 282
Xuewen Wang et al.

Figure 8.19: (a) SEM images of woodpile structures fabricated by TPL and representative images of cell adhesion.
Autofluorescence (red), phalloidin (magenta) and hoechst (blue) was used to mark woodpile structure, cells and
nuclei, respectively. Reproduced with permission from [84]. Copyright 2017 Elsevier Science and Technology Journals.
(b) Confocal fluorescence and SEM image of grid scaffold which mitochondrial regions of cells was selectively dyed to
deep red. Reproduced with permission from [117]. Copyright 2019 American Chemical Society. (c) SEM images of
fabricated microrobots (microswimmers). (d) The process of swimmers approach motion. Reproduced with permission
from [80]. Copyright 2016 John Wiley and Sons Books.
 Chapter 8 Functional 3D nanoprinting via femtosecond laser nonlinear lithography 283

recent years, benefitting from materials and structural design, biomicrorobots have
been able to perform more and more interesting functions, which is a direct result of
adding TPL to various materials.
Tissue engineering is a multifaceted application that combines materials, cells
and biological environments. It aims to produce a scaffold as biological substitute
for damaged tissue. There are several rules that should be considered before fabri-
cation: (i) suitable biocompatibility and biodegradability, enough mechanical sta-
bility to support the attached cells; (ii) interconnected networks so that cells can be
adhered and allowed to proliferate and migrate deeply; (iii) nutrients and oxygen
that can easily reach cells through the network, and cellular waste products can
also be easily excreted [112, 113].
As an excellent technology allowing preciseness and a high degree of freedom,
TPL can fabricate a macroscopic scaffold and apply it to neural tissue engineering
to help nerve repair. Koroleba et al. used photopolymerizable polylactic acid (PLA)
to produce scaffolds [114]. Through a wide biocompatibility study, the photocured
PLA scaffold was demonstrated to support primary cell growth, which proved that
it could be applied into neural tissue engineering appropriately. Deeply benefitting
from cross-linked PEGDA and hyaluronic acid, a scaffold was fabricated for efficient
colonization of neuro cells and 3D confocal imaging [115]. Recently, the passage of
foreign substances through the blood-brain barrier (BBB) has attracted widespread
attention in the field of biomedicine [116]. Using nonlinear lithography, a type of
microtube inspired by the brain capillaries was fabricated into a BBB model, and it
performed well in terms of hindering dextran diffusion through the barrier. It is ex-
pected to be used in treating and diagnosing a variety of brain diseases, including
brain cancer.
Zheng et al. introduced a novel water-soluble photoinitiator that could effectively
improve cross-section absorption [117]. And then, a hydrogel scaffold was fabricated
and proved to show the potential of cell culture and observation (Figure 8.19(b)).

8.5.3 Microelectronics

The preparation of high-performance 3D printable conductive materials is of great

significance to the development of MEMS. Among the many 3D printing technologies,
TPL has the smallest spatial resolution and plays an important role to manufacture
the smallest conductive devices [118]. The critical point of making a cross-linked net-
work with conductive properties is that it can hold nanoparticles (NPs) and allow
charge transfer.
The most direct way to obtain conductive properties is to add conductive compo-
nents to the photoresist to form a hybrid material. Among them, a mixed photoresist
composed of carbon nanotubes (CNT) has been studied a lot, because of its reason-
able conductivity [119]. Staudinger et al. mixed single-walled carbon nanotubes
284 Xuewen Wang et al.

(SW-CNT) with commercial photoresist equably to fabricate a few microstructures

that demonstrated the viability of fabricating conductive microdevices using femto-
second laser and nanocomposites [120]. Similarly, Xiong and his coworkers developed
a method to fabricate 3D conductive structures through incorporating a large-amount
of well-aligned multiwalled carbon nanotubes (MWNTs) into photoresists [119]. To
demonstrate the potential of TPL fabrication in MEMS, they prepared a variety of con-
ductive microelectronic devices, including arrays of capacitors (Figure 8.20(a)) and re-
sistors (Figure 8.20(b)), which could be fabricated on the polyethylene terephthalate
(PET) substrate (Figure 8.20(c)). The network generated by the dispersed nanotubes
resulted in reasonable conductivity. Their works pave the way towards fabrication of
precise micro/nano architectures in applications of MEMS/NEMS.

Figure 8.20: Optical micrographs of a capacitor (a) and a resistor (b) with different structural
arrays. (c) A bent PET substrate used for MEMS. (d) SEM image of perpendicular connections
between four gold pads. Reproduced with permission from [119, 123]. Copyright 2016 John Wiley
and Sons.

Another effective method to make fabricated structures conductive consists of photo-

induced reduction of metal ions. The use of ultrafast laser can induce photoreduction
of metal ions in the presence of a photosensitizer, while printing 3D structures. It has
 Chapter 8 Functional 3D nanoprinting via femtosecond laser nonlinear lithography 285

been investigated in directly writing metal structures in solution or mixing in a poly-

mer matrix to form conductive architectures. Taking advantage of commercial photo-
resist and photoinitiator containing HAuCl4, Shukla et al. and Nakamura et al. wrote
conductive patterns characterized by high conductivity [121, 122]. They demonstrated
that the HAuCl4-doped photosensitizer could induce the reduction and aggregation
of gold ions by two-photon absorption when the laser was irradiated, while only
cross-link a small amount of SU-8. Remarkably, Blasco et al. replaced SU-8 with
PEG-based photoresist that Au could be photoreduced, while two-photon poly-
merizing the cross-linking network. They successfully fabricated conductive 3D
wires that connected different gold pads and showed conductivity as high as bulk
gold (2.2 × 106 S m−1, Figure 8.20(d)) [123].
Piezoelectric effect means that when certain dielectrics are deformed by exter-
nal forces in a certain direction, polarization will occur inside them, and at the
same time, positive and negative charges will appear on its two opposite surfaces.
In histological applications, the appearance of piezoelectric effect can stimulate
cell stimulation and differentiation [10, 124]. Marino et al. fabricated bioinspired 3D
structures (Osteo-prints) with a nanocomposite resist, Ormocomp, containing 10%
piezoelectric barium titanate NPs (BTNPs). Under mechanical simulation, these
scaffolds could enhance the osteogenic differentiation of SaOS-2 bone-like cells.
This ability to feed mechanical action back to electrical stimulation was expected to
be used for tissue and cell control [124].

8.5.4 Microoptics

There are many interesting applications in the field of optical and photonic devices
including on-demand complex (micro) structures with high refractive index (n) and
tailored bandgap. The properties of light beam carrying angular momentum have
been investigated from the research of quantum optics to microscopy and microma-
nipulation. Femtosecond laser nonlinear lithography to modify the microstructure
of optical components can achieve peculiar phenomena [10].
Beresna et al. produced a radical polarizer that could generate optical vortices on
a small scale, using femtosecond laser corrosion [125]. They demonstrated that the
orbital angular momentum could appear in the micro voids after nonlinear lithogra-
phy. Because of angular momentum conservation, the spherical interface would
cause the generation of optical vortices. This technology provided a new idea for the
development of radial polarizers. Following this thought, Wei et al. prepared micro-
scale spiral phase structures that could generate orbital-angular momentum light.
Moreover, for real applications, TPL could fabricate spiral phase plates at different
operating wavelengths to fit various work environments [126].
286 Xuewen Wang et al.

As a high-resolution 3D manufacturing technology, TPL has become the main

method for the fabrication of nanophotonic devices. Photonic crystal is an artificial
periodic dielectric structure that can be precisely controlled by nonlinear lithogra-
phy. Rybin et al. investigated several types of 3D photonic crystals and found that
the complete photonic band gap appears in the inverted opal (Figure 8.21(a)) [127].
They demonstrated that changes of complete photonic band gap were relative to
different woodpile structures, which indicated the optical tunable properties via
this technology. Similarly, Greer’s group proposed a new method to create complex
ceramics through nonlinear lithography and pyrolysis [66]. Taking advantage of
high refractive index of Ti02 and using Ti-containing photoresist, they prepared a
photonic crystal with all photonic band gaps. It is worth noting that they combined
controllable ceramic shrinkage with nonlinear lithography to precisely control the
microscopic morphology of the photonic crystal. As a controllable technology, Pur-
tov et al. fabricated a series of nanopillar diffraction gratings by changing laser
power (Figure 8.21(b)) [128]. They proved that the color would change towards a
blueish hue gradually, when the pillar size increased.

Figure 8.21: (a) Woodpile crystals with specific filling factor (w/a = 0.28) and the photonic band
structure. Reproduced with permission from [127]. Copyright 2015 MDPI. (b) Optical appearance
and SEM images of nanopillar gratings under different laser power. Reproduced with permission
from [128]. Copyright 2018 MDPI. (c) SEM image of a photonic follower. (d) Crossed polarized
micrographs of photonic flower response to temperature and humidity. RH, relative humidity.
Reproduced with permission from [130]. Copyright 2020 American Chemical Society.
 Chapter 8 Functional 3D nanoprinting via femtosecond laser nonlinear lithography 287

TPL based on nonlinear absorption is also suitable for nanofabrication of inte-

grated photonics devices [129]. Besides, 4D structural color microactuators also can
be printed by using a photonic photoresist (Figure 8.21(c)) [130]. It would change
color and structure with variation in temperature or humidity, which showed dual-
response (Figure 8.21(d)). Figure 8.21(d) shows the dynamic response in the flower
structure’s height with changes in humidity or temperature. It is supposed to belong
to the actuation, but it can also act as a photonic device. It proved that variations in
the reflection band were related to changes of the ordered cholesteric liquid crystals
(CLC), which was triggered by expansion. This is a kind of four-dimensional photon
microactuator with great potential.

8.6 Conclusions and perspectives

As mentioned before, TPL is based on the mature femtosecond laser technology.
The development of TPL is not only depend on the establishment of two-photon ab-
sorption and two-photon polymerization theoretical system, but also on the output of
femtosecond laser, a key device. As for the photoresist, scholars are no longer limited
to commercial materials, but exploring a variety of methods to enrich characteristics
and apply them into more fields.
Starting from the principle of nonlinear lithography, this chapter introduces
methods for controlling resolution and efficiency in 3D manufacturing. Later, based
on recent research, several photoresists currently used have been introduced. The
composition of photoresist is not complex – it must contain photoinitiator and poly-
merized monomer, but the preparation of photoresist with excellent performance
still needs continuous exploration. The ultimate goal of these studies is to be appli-
cable in various fields.
In the past few years, researches based on this 3D additive manufacturing tech-
nology have shown explosive growth. This proves that it has a wide range applica-
tions and infinite developing potential in science and industry. Among the various
3D manufacturing technologies, TPL has the highest precision, accurately fabricat-
ing complex structures with a resolution exceeding the diffraction limit and open-
ing a new world in architecture and applications.
However, while further expanding the scope of application of nonlinear lithogra-
phy, some problems still remain. TPL has lower speed of fabrication compared to other
3D additive manufacturing technologies. Moreover, it takes a tedious process and a
lot of time to get a complete and usable device. These shortcomings prevent this tech-
nology from being widely used in industrial fabrication. But, we believe that it will
lead the industrial micro/nanofabrication to a higher level. Scholars are also constantly
optimizing the process and increasing its manufacturing efficiency. Once the condi-
tions are met, it will inevitably be integrated into various aspects of life.
288 Xuewen Wang et al.

References
[1] Hohmann, J. K., Renner, M., Waller, E. H., von Freymann, G. Three-dimensional μ-printing: An
enabling technology, Adv Opt Mater, 2015, 3, 1488–1507.
[2] Tommaso, B. Three-dimensional microfabrication using two-photon polymerization:
fundamentals, technology, and applications, Matthew Deans: USA, 2016.
[3] Zhang, Y.-L., Chen, Q.-D., Xia, H., Sun, H.-B. Designable 3D nanofabrication by femtosecond
laser direct writing, Nano Today, 2010, 5, 435–448.
[4] Wang, X. W., Kuchmizhak, A. A., Brasselet, E., Juodkazis, S. Dielectric geometric phase
optical elements fabricated by femtosecond direct laser writing in photoresists, Appl Phys
Lett, 2017, 110, 4.
[5] Wang, X. W., Kuchmizhak, A., Storozhenko, D., Makarov, S., Juodkazis, S. Single-step laser
plasmonic coloration of metal films, ACS Appl Mater Interfaces, 2018, 10, 1422–1427.
[6] Wang, X. W., Kuchmizhak, A. A., Li, X., Juodkazis, S., Vitrik, O. B., Kulchin, Y. N., Zhakhovsky,
V. V., Danilov, P. A., Ionin, A. A., Kudryashov, S. I., Rudenko, A. A., Inogamov, N. A. Laser-
induced translative hydrodynamic mass snapshots: Noninvasive characterization and
predictive modeling via mapping at nanoscale, Phys Rev Appl, 2017, 8, 17.
[7] Malinauskas, M., Farsari, M., Piskarskas, A., Juodkazis, S. Ultrafast laser nanostructuring of
photopolymers: A decade of advances, Phys Rep, 2013, 533, 1–31.
[8] Ovsianikov, A., Mironov, V., Stampf, J., Liska, R. Engineering 3D cell-culture matrices:
Multiphoton processing technologies for biological and tissue engineering applications,
Expert Rev Med Devices, 2012, 9, 613–633.
[9] Xing, J. F., Zheng, M. L., Duan, X. M. Two-photon polymerization microfabrication of
hydrogels: An advanced 3D printing technology for tissue engineering and drug delivery,
Chem Soc Rev, 2015, 44, 5031–5039.
[10] Carlotti, M., Mattoli, V. Functional materials for two-photon polymerization in
microfabrication, Small, 2019, 15, e1902687.
[11] Sakellari, I., Kabouraki, E., Gray, D., Purlys, V., Fotakis, C., Pikulin, A., Bityurin, N.,
Vamvakaki, M., Farsari, M. Diffusion-assisted high-resolution direct femtosecond laser
writing, ACS Nano, 2012, 6, 2302–2311.
[12] Li, L., Gattass, R. R., Gershgoren, E., Hwang, H., Fourkas, J. T. Achieving lambda/20
resolution by one-color initiation and deactivation of polymerization, Science, 2009, 324,
910–913.
[13] Goppert-Mayer, M. Uber Elementarakte mit zwei quantensprungen, 1931, 273–294.
[14] Kaiser, W. K., Garrett, C. G. B. 2-Photon excitation in Caf2 – Eu2+, Phys Rev Lett, 1961,
7, 229–231.
[15] Marius, A. D. B., Jean-Luc, B., Jeffrey, E., Jia-Ying, F., Ahmed, A. H., Hess, S. E., Kogej, T.,
Levin, M. D., Marder, S. R., McCord-Maughon, D., Perry, J. W., Rockel, H., Rumi, M.,
Subramaniam, G., Watt, W. W., Xiang-Li, W., Chris, X. Design of organic molecules with large
two-photon absorption cross Sections, Science, 1998, 281, 1653–1656.
[16] Cumpston, B. H., Ananthavel, S. P., Barlow, S., Dyer, D. L., Ehrlich, J. E., Erskine, L. L., Heikal,
A. A., Kuebler, S. M., Lee, I. Y. S., McCord-Maughon, D., Qin, J., Röckel, H., Rumi, M., Wu,
X.-L., Marder, S. R., Perry, J. W. Two-photon polymerization initiators for three-dimensional
optical data storage and microfabrication, Nature, 1999, 398, 51–54.
[17] Wood, D. Microstereolithography and other fabrication techniques for 3D MEMS [Book
Review], Eng Sci Educ J, 2002, 11, 65–65.
[18] Boyd, R. W. Nonlinear optics, Third edn, Academic Press: Burlington, 2008.
[19] LaFratta, C. N., Fourkas, J. T., Baldacchini, T., Farrer, R. A. Multiphoton fabrication, Angew
Chem Int Ed Engl, 2007, 46, 6238–6258.
 Chapter 8 Functional 3D nanoprinting via femtosecond laser nonlinear lithography 289

[20] Maruo, S., Nakamura, O., Kawata, S. Three-dimensional microfabrication with two-photon-
absorbed photopolymerization, Opt Lett, 1997, 22, 132–134.
[21] Sun, H.-B., Kawata, S. NMR 3D Analysis Photopolymerization. 2006.
[22] Fischer, J., Wegener, M. Three-dimensional direct laser writing inspired by stimulated-
emission-depletion microscopy [Invited], Opt Mater Express, 2011, 1, 614–624.
[23] He, G. S., Tan, L. S., Zheng, Q., Prasad, P. N. Multiphoton absorbing materials: Molecular
designs, characterizations, and applications, Chem Rev, 2008, 108, 1245–1330.
[24] Wu, S., Serbin, J., Gu, M. Two-photon polymerisation for three-dimensional micro-fabrication,
J Photochem Photobiol A Chem, 2006, 181, 1–11.
[25] Park, S. H., Yang, D. Y., Lee, K. S. Two-photon stereolithography for realizing ultraprecise
three-dimensional nano/microdevices, Laser Photon Rev, 2009, 3, 1–11.
[26] Xing, J., Liu, J., Zhang, T., Zhang, L., Zheng, M., Duan, X. A water soluble initiator prepared
through host-guest chemical interaction for microfabrication of 3D hydrogels via two-photon
polymerization, J Mater Chem B, 2014, 2, 4318–4323.
[27] Dong, X.-Z., Zhao, Z.-S., Duan, X.-M. Improving spatial resolution and reducing aspect ratio
in multiphoton polymerization nanofabrication, Appl Phys Lett, 2008, 92, 091113.
[28] Bourdon, L., Maurin, J.-C., Gritsch, K., Brioude, A., Salles, V. Improvements in resolution of
additive manufacturing: Advances in two-photon polymerization and direct-writing
electrospinning techniques, ACS Biomater Sci Eng, 2018, 4, 3927–3938.
[29] Born, M. Book principles of optics – electromagnetic theory of propagation, interference and
diffraction of light, Astronomische Nachrichten, 1980, 301.
[30] Zhou, X., Hou, Y., Lin, J. A review on the processing accuracy of two-photon polymerization,
AIP Adv, 2015, 5, 030701.
[31] Yang, Z.-J., Zhang, S.-M., Li, X.-L., Pang, Z.-G. Variable sinh-Gaussian solitons in nonlocal
nonlinear Schrödinger equation, Appl Math Lett, 2018, 82, 64–70.
[32] Juodkazis, S., Mizeikis, V., Seet, K. K., Miwa, M., Misawa, H. Two-photon lithography of
nanorods in SU-8 photoresist, Nanotechnology, 2005, 16, 846–849.
[33] Tan, D., Li, Y., Qi, F., Yang, H., Gong, Q., Dong, X., Duan, X. Reduction in feature size of
two-photon polymerization using SCR500, Appl Phys Lett, 2007, 90, 71106.
[34] Kawata, S., Sun, H.-B., Tanaka, T., Takada, K. Finer features for functional microdevices,
Nature, 2001, 412, 697–698.
[35] Wang, S., Yu, Y., Liu, H., Lim, K. T. P., Srinivasan, B. M., Zhang, Y. W., Yang, J. K. W. Sub-10-
nm suspended nano-web formation by direct laser writing, Nano Futures, 2018, 2, 025006.
[36] Park, S. H., Lim, T. W., Yang, D.-Y., Kim, R. H., Lee, K.-S. Improvement of spatial resolution in
nano-stereolithography using radical quencher, Macromol Res, 2006, 14, 559–564.
[37] Takada, K., Sun, H.-B., Kawata, S. Improved spatial resolution and surface roughness in
photopolymerization-based laser nanowriting, Appl Phys Lett, 2005, 86, 071122.
[38] Xing, J.-F., Dong, X.-Z., Chen, W.-Q., Duan, X.-M., Takeyasu, N., Tanaka, T., Kawata,
S. Improving spatial resolution of two-photon microfabrication by using photoinitiator with
high initiating efficiency, Appl Phys Lett, 2007, 90, 131106.
[39] Peng, Y., Jradi, S., Yang, X., Dupont, M., Hamie, F., Dinh, X. Q., Sun, X. W., Xu, T., Bachelot,
R. 3D photoluminescent nanostructures containing quantum dots fabricated by two-photon
polymerization: Influence of quantum dots on the spatial resolution of laser writing, Adv
Mater Technol, 2019, 4, 1800522.
[40] Fischer, J., Wegener, M. Three-dimensional optical laser lithography beyond the diffraction
limit, Laser Photon Rev, 2013, 7, 22–44.
[41] Yaoyu, C., Zongsong, G., Baohua, J., Evans, R. A., Min, G. High-photosensitive resin for
super-resolution direct-laser-writing based on photoinhibited polymerization, Opt Express, 2011,
19, 19486.
290 Xuewen Wang et al.

[42] Fischer, J., Von, Freymann, G., Martin, W. The materials challenge in diffraction-unlimited
direct-laser-writing optical lithography, Adv Mater, 2010, 22, 3578–3582.
[43] Wollhofen, R., Katzmann, J., Hrelescu, C., Jacak, J., Klar, T. A. 120 nm resolution and 55 nm
structure size in STED-lithography, Opt Express, 2013, 21, 10831–10840.
[44] Bae, W. G., Kim, H. N., Kim, D., Park, S. H., Jeong, H. E., Suh, K. Y. 25th anniversary article:
scalable multiscale patterned structures inspired by nature: The role of hierarchy, Adv Mater,
2014, 26, 675–700.
[45] Hasegawa, S., Hayasaki, Y. Holographic vector wave femtosecond laser processing, Int J
Optomechatronics, 2014, 8, 73–88.
[46] Yang, L., El-Tamer, A., Hinze, U., Li, J., Hu, Y., Huang, W., Chu, J., Chichkov, B. N. Parallel
direct laser writing of micro-optical and photonic structures using spatial light modulator,
Opt Lasers Eng, 2015, 70, 26–32.
[47] Abid, M. I., Wang, L., Chen, Q.-D., Wang, X.-W., Juodkazis, S., Sun, H.-B. Angle-multiplexed
optical printing of biomimetic hierarchical 3D textures, Laser Photon Rev, 2017, 11, 1600187.
[48] Wang, P., Chu, W., Li, W., Tan, Y., Liu, F., Wang, M., Qi, J., Lin, J., Zhang, F., Wang, Z., Cheng,
Y. Three-dimensional laser printing of macro-scale glass objects at a micro-scale resolution,
Micromachines (Basel), 2019, 10, 565.
[49] Saha, S. K., Wang, D., Nguyen, V. H., Chang, Y., Oakdale, J. S., Chen, S. C. Scalable
submicrometer additive manufacturing, Science, 2019, 366, 105–109.
[50] Selimis, A., Mironov, V., Farsari, M. Direct laser writing: Principles and materials for scaffold
3D printing, Microelectron Eng, 2015, 132, 83–89.
[51] Maruo, S., Nakamura, O., Kawata, S. Three-dimensional microfabrication with two-photon-
absorbed photopolymerization, Ol/22/2/ol Pdf, 1997, 22, 132–0.
[52] Tayalia, P., Mendonca, C. R., Baldacchini, T., Mooney, D. J., Mazur, E. 3D cell-migration
studies using two-photon engineered polymer scaffolds, Adv Mater, 2008, 20, 4494–4498.
[53] Weiß, T., Schade, R., Laube, T., Berg, A., Hildebrand, G., Wyrwa, R., Schnabelrauch, M.,
Liefeith, K. Two-photon polymerization of biocompatible photopolymers for microstructured
3D biointerfaces, Adv Eng Mater, 2011, 13, B264–B73.
[54] Ummethala, G., Jaiswal, A., Chaudhary, R. P., Hawal, S., Saxena, S., Shukla, S. Localized
polymerization using single photon photoinitiators in two-photon process for fabricating
subwavelength structures, Polymer, 2017, 117, 364–369.
[55] Juodkazis, S., Mizeikis, V., Misawa, H. Three-dimensional microfabrication of materials by
femtosecond lasers for photonics applications, J Appl Phys, 2009, 106, 051101.
[56] Sabel, T. Volume hologram formation in SU-8 photoresist, Polymers (Basel), 2017, 9, 198.
[57] Zhang, J., Tan, K. L., Hong, G. D., Yang, L. J., Gong, H. Q. Polymerization optimization of
SU-8 photoresist and its applications in microfluidic systems and MEMS, J Micromech
Microeng, 2001, 11, 20–26.
[58] Ovsianikov, A., Schlie, S., Ngezahayo, A., Haverich, A., Chichkov, B. N. Two-photon
polymerization technique for microfabrication of CAD-designed 3D scaffolds from
commercially available photosensitive materials, J Tissue Eng Regen Med, 2007, 1, 443–449.
[59] Accoto, C., Qualtieri, A., Pisanello, F., Ricciardi, C., Pirri, C. F., Vittorio, M. D., Rizzi, F.
Two-photon polymerization lithography and laser doppler vibrometry of a SU-8-based
suspended microchannel resonator, J Microelectromech Syst, 2015, 24, 1038–1042.
[60] Li, J. Y., Li, X. J., Luo, T., Wang, R., Liu, C. C., Chen, S. X., Li, D. F., Yue, J. B., Cheng, S. H., Sun,
D. Development of a magnetic microrobot for carrying and delivering targeted cells, Sci
Robot, 2018, 3, 11.
[61] Farsari, M., Vamvakaki, M., Chichkov, B. N. Multiphoton polymerization of hybrid materials,
J Opt, 2010, 12, 124001.
 Chapter 8 Functional 3D nanoprinting via femtosecond laser nonlinear lithography 291

[62] Dinca, V., Kasotakis, E., Catherine, J., Mourka, A., Ranella, A., Ovsianikov, A., Chichkov, B. N.,
Farsari, M., Mitraki, A., Fotakis, C. Directed three-dimensional patterning of self-assembled
peptide fibrils, Nano Lett, 2008, 8, 538–543.
[63] Farsari, M., Chichkov, B. N. Two-photon fabrication, Nat Photonics, 2009, 3, 450–452.
[64] Ovsianikov, A., Viertl, J., Chichkov, B., Oubaha, M., MacCraith, B., Sakellari, I., Giakoumaki,
A., Gray, D., Vamvakaki, M., Farsari, M., Fotakis, C. Ultra-low shrinkage hybrid photosensitive
material for two-photon polymerization microfabrication, ACS Nano, 2008, 2, 2257–2262.
[65] Vyatskikh, A., Kudo, A., Delalande, S., Greer, J. R. Additive manufacturing of polymer-derived
titania for one-step solar water purification, Mater Today Commun, 2018, 15, 288–293.
[66] Vyatskikh, A., Ng, R. C., Edwards, B., Briggs, R. M., Greer, J. R. Additive manufacturing of
high-refractive-index, nanoarchitected titanium dioxide for 3D dielectric photonic crystals,
Nano Lett, 2020, 20, 3513–3520.
[67] Dinachali, S. S., Dumond, J., Saifullah, M. S., Ansah-Antwi, K. K., Ganesan, R., Thian, E. S.,
He, C. Large area, facile oxide nanofabrication via step-and-flash imprint lithography of
metal-organic hybrid resins, ACS Appl Mater Interfaces, 2013, 5, 13113–13123.
[68] Drury, J. L., Mooney, D. J. Hydrogels for tissue engineering: Scaffold design variables and
applications, Biomaterials, 2003, 24, 4337–4351.
[69] Liao, C., Wuethrich, A., Trau, M. A material odyssey for 3D nano/microstructures: Two photon
polymerization based nanolithography in bioapplications, Appl Mater Today, 2020, 19,
100635.
[70] You, S., Li, J., Zhu, W., Yu, C., Mei, D., Chen, S. Nanoscale 3D printing of hydrogels for
cellular tissue engineering, J Mater Chem B, 2018, 6, 2187–2197.
[71] Pennacchio, F. A., Fedele, C., De Martino, S., Cavalli, S., Vecchione, R., Netti, P. A. Three-
dimensional microstructured azobenzene-containing gelatin as a photoactuable cell
confining system, ACS Appl Mater Interfaces, 2018, 10, 91–97.
[72] Park, J., Jin, C., Lee, S., Kim, J. Y., Choi, H. Magnetically actuated degradable microrobots for
actively controlled drug release and hyperthermia therapy, Adv Healthc Mater, 2019, 8,
e1900213.
[73] Lv, C., Sun, X.-C., Xia, H., Yu, Y.-H., Wang, G., Cao, X.-W., Li, S.-X., Wang, Y.-S., Chen, Q.-D.,
Yu, Y.-D., Sun, H.-B. Humidity-responsive actuation of programmable hydrogel
microstructures based on 3D printing, Sens Actuators B Chem, 2018, 259, 736–744.
[74] Olsen, M. H., Hjorto, G. M., Hansen, M., Met, O., Svane, I. M., Larsen, N. B. In-chip
fabrication of free-form 3D constructs for directed cell migration analysis, Lab Chip, 2013,
13, 4800–4809.
[75] Witzgall, V., Yablonovitch, D. Single-shot two-photon exposure of commercial photoresist for
the production of three-dimensional structures, Opt Lett, 1998, 23, 1745–1747.
[76] Teh, W. H., Dürig, U., Salis, G., Harbers, R., Drechsler, U., Mahrt, R. F., Smith, C. G.,
Güntherodt, H. J. SU-8 for real three-dimensional subdiffraction-limit two-photon
microfabrication, Appl Phys Lett, 2004, 84, 4095–4097.
[77] Duan, X.-M., Sun, H.-B., Kaneko, K., Kawata, S. Two-photon polymerization of metal ions
doped acrylate monomers and oligomers for three-dimensional structure fabrication, Thin
Solid Films, 2004, 453–454, 518–521.
[78] Wloka, T., Czich, S., Kleinsteuber, M., Moek, E., Weber, C., Gottschaldt, M., Liefeith, K.,
Schubert, U. S. Microfabrication of 3D-hydrogels via two-photon polymerization of
poly(2-ethyl-2-oxazoline) diacrylates, Eur Polym J, 2020, 122, 109295.
[79] Xiong, Z., Zheng, C., Jin, F., Wei, R., Zhao, Y., Gao, X., Xia, Y., Dong, X., Zheng, M., Duan,
X. Magnetic-field-driven ultra-small 3D hydrogel microstructures: Preparation of gel photoresist
and two-photon polymerization microfabrication, Sens Actuators B Chem, 2018, 274, 541–550.
292 Xuewen Wang et al.

[80] Peters, C., Hoop, M., Pane, S., Nelson, B. J., Hierold, C. Degradable magnetic composites for
minimally invasive interventions: Device fabrication, targeted drug delivery, and cytotoxicity
tests, Adv Mater, 2016, 28, 533–538.
[81] Huang, Q.-L., Xu, H.-L., Li, M.-T., Hou, Z.-S., Lv, C., Zhan, X.-P., Li, H.-L., Xia, H., Wang, H.-Y.,
Sun, H.-B. Stretchable PEG-DA hydrogel-based whispering-gallery-mode microlaser with
humidity responsiveness, J Lightwave Technol, 2018, 36, 819–824.
[82] Scarpa, E., Lemma, E. D., Fiammengo, R., Cipolla, M. P., Pisanello, F., Rizzi, F., De
Vittorio, M. Microfabrication of pH-responsive 3D hydrogel structures via two-photon
polymerization of high-molecular-weight poly(ethylene glycol) diacrylates, Sens Actuators B
Chem, 2019, 279, 418–426.
[83] Hasselmann, N. F., Hackmann, M. J., Horn, W. Two-photon fabrication of hydrogel
microstructures for excitation and immobilization of cells, Biomed Microdevices, 2017, 20, 8.
[84] Brigo, L., Urciuolo, A., Giulitti, S., Della Giustina, G., Tromayer, M., Liska, R., Elvassore, N.,
Brusatin, G. 3D high-resolution two-photon crosslinked hydrogel structures for biological
studies, Acta Biomater, 2017, 55, 373–384.
[85] Wang, X., Qin, X.-H., Hu, C., Terzopoulou, A., Chen, X.-Z., Huang, T.-Y., Maniura-Weber, K.,
Pané, S., Nelson, B. J. 3D printed enzymatically biodegradable soft helical microswimmers,
Adv Funct Mater, 2018, 28, 1804107.
[86] Ceylan, H., Yasa, I. C., Yasa, O., Tabak, A. F., Giltinan, J., Sitti, M. 3D-printed biodegradable
microswimmer for theranostic cargo delivery and release, ACS Nano, 2019, 13, 3353–3362.
[87] Pitts, J. D., Howell, A. R., Taboada, R., Banerjee, I., Wang, J., Goodman, S. L., Campagnola,
P. J. New photoactivators for multiphoton excited three-dimensional submicron cross-linking
of proteins: Bovine serum albumin and type 1 collagen¶†, Photochem Photobiol, 2002, 76,
135–144.
[88] Seidlits, S. K., Schmidt, C. E., Shear, J. B. High-resolution patterning of hydrogels in three
dimensions using direct-write photofabrication for cell guidance, Adv Funct Mater, 2009,
19, 3543–3551.
[89] Ritschdorff, E. T., Shear, J. B. Multiphoton lithography using a high-repetition rate microchip
laser, Anal Chem, 2010, 82, 8733–8737.
[90] Turunen, S., Kapyla, E., Terzaki, K., Viitanen, J., Fotakis, C., Kellomaki, M., Farsari, M. Pico-
and femtosecond laser-induced crosslinking of protein microstructures: Evaluation of
processability and bioactivity, Biofabrication, 2011, 3, 045002.
[91] Berg, A., Wyrwa, R., Weisser, J., Weiss, T., Schade, R., Hildebrand, G., Liefeith, K., Schneider,
B., Ellinger, R., Schnabelrauch, M. Synthesis of photopolymerizable hydrophilic macromers
and evaluation of their applicability as reactive resin components for the fabrication of three-
dimensionally structured hydrogel matrices by 2-photon-polymerization, Adv Eng Mater,
2011, 13, B274–B84.
[92] Ovsianikov, A., Deiwick, A., Van Vlierberghe, S., Dubruel, P., Moller, L., Drager, G., Chichkov,
B. Laser fabrication of three-dimensional CAD scaffolds from photosensitive gelatin for
applications in tissue engineering, Biomacromolecules, 2011, 12, 851–858.
[93] Qin, X.-H., Torgersen, J., Saf, R., Mühleder, S., Pucher, N., Ligon, S. C., Holnthoner, W., Redl,
H., Ovsianikov, A., Stampfl, J., Liska, R. Three-dimensional microfabrication of protein
hydrogels via two-photon-excited thiol-vinyl ester photopolymerization, J Polym Sci A Polym
Chem, 2013, 51, 4799–4810.
[94] Loebel, C., Broguiere, N., Alini, M., Zenobi-Wong, M., Eglin, D. Microfabrication of
photo-cross-linked hyaluronan hydrogels by single- and two-photon tyramine oxidation,
Biomacromolecules, 2015, 16, 2624–2630.
[95] Yulianto, E., Chatterjee, S., Purlys, V., Mizeikis, V. Imaging of latent three-dimensional exposure
patterns created by direct laser writing in photoresists, Appl Surf Sci, 2019, 479, 822–827.
 Chapter 8 Functional 3D nanoprinting via femtosecond laser nonlinear lithography 293

[96] Kaschke, J., Wegener, M. Optical and infrared helical metamaterials, Nanophotonics, 2016,
5, 510–523.
[97] Kadic, M., Bückmann, T., Stenger, N., Thiel, M., Wegener, M. On the practicability of
pentamode mechanical metamaterials, Appl Phys Lett, 2012, 100, 191901.
[98] Buckmann, T., Thiel, M., Kadic, M., Schittny, R., Wegener, M. An elasto-mechanical
unfeelability cloak made of pentamode metamaterials, Nat Commun, 2014, 5, 4130.
[99] Frenzel, T., Kadic, M., Wegener, M. Three-dimensional mechanical metamaterials with a
twist, Science, 2017, 358, 1072–1074.
[100] Portela, C. M., Greer, J. R., Kochmann, D. M. Impact of node geometry on the effective stiffness of
non-slender three-dimensional truss lattice architectures, Extreme Mech Lett, 2018, 22, 138–148.
[101] Tancogne-Dejean, T., Diamantopoulou, M., Gorji, M. B., Bonatti, C., Mohr, D. 3D plate-
lattices: An emerging class of low-density metamaterial exhibiting optimal isotropic
stiffness, Adv Mater, 2018, 30, e1803334.
[102] Crook, C., Bauer, J., Guell Izard, A., Santos de Oliveira, C., Martins de Souza, E. S. J., Berger,
J. B., Valdevit, L. Plate-nanolattices at the theoretical limit of stiffness and strength, Nat
Commun, 2020, 11, 1579.
[103] Oakdale, J. S., Smith, R. F., Forien, J.-B., Smith, W. L., Ali, S. J., Bayu Aji, L. B., Willey, T. M.,
Ye, J., van Buuren, A. W., Worthington, M. A., Prisbrey, S. T., Park, H.-S., Amendt, P. A.,
Baumann, T. F., Biener, J. Direct laser writing of low-density interdigitated foams for plasma
drive shaping, Adv Funct Mater, 2017, 27, 1702425.
[104] Tian, Y., Zhang, Y. L., Xia, H., Guo, L., Ku, J. F., He, Y., Zhang, R., Xu, B. Z., Chen, Q. D., Sun,
H. B. Solvent response of polymers for micromachine manipulation, Phys Chem Phys, 2011,
13, 4835–4838.
[105] Hippler, M., Blasco, E., Qu, J., Tanaka, M., Barner-Kowollik, C., Wegener, M.,
Bastmeyer, M. Controlling the shape of 3D microstructures by temperature and light, Nat
Commun, 2019, 10, 232.
[106] Li, M. H., Keller, P., Li, B., Wang, X., Brunet, M. Light-driven side-on nematic elastomer
actuators, Adv Mater, 2003, 15, 569–572.
[107] Zeng, H., Martella, D., Wasylczyk, P., Cerretti, G., Lavocat, J. C., Ho, C. H., Parmeggiani, C.,
Wiersma, D. S. High-resolution 3D direct laser writing for liquid-crystalline elastomer
microstructures, Adv Mater, 2014, 26, 2319–2322.
[108] Descrovi, E., Pirani, F., . P., Rajamanickam, V., Licheri, S., Liberale, C. Photo-responsive
suspended micro-membranes, J Mater Chem C, 2018, 6, 10428–10434.
[109] Barbot, A., Power, M., Seichepine, F., Yang, G. Z. Liquid seal for compact micropiston
actuation at the capillary tip, Sci Adv, 2020, 6, 8.
[110] Yi, S., Ding, F., Gong, L., Gu, X. Extracellular matrix scaffolds for tissue engineering and
regenerative medicine, Curr Stem Cell Res Ther, 2017, 12, 233–246.
[111] Nelson, B. J., Kaliakatsos, I. K., Abbott, J. J. Microrobots for minimally invasive medicine,
Annu Rev Biomed Eng, 2010, 12, 55–85.
[112] Billiet, T., Vandenhaute, M., Schelfhout, J., Van Vlierberghe, S., Dubruel, P. A review of
trends and limitations in hydrogel-rapid prototyping for tissue engineering, Biomaterials,
2012, 33, 6020–6041.
[113] Yeong, W. Y., Chua, C. K., Leong, K. F., Chandrasekaran, M. Rapid prototyping in tissue
engineering: Challenges and potential, Trends Biotechnol, 2004, 22, 643–652.
[114] Koroleva, A., Gill, A. A., Ortega, I., Haycock, J. W., Schlie, S., Gittard, S. D., Chichkov, B. N.,
Claeyssens, F. Two-photon polymerization-generated and micromolding-replicated 3D scaffolds
for peripheral neural tissue engineering applications, Biofabrication, 2012, 4, 025005.
294 Xuewen Wang et al.

[115] Accardo, A., Blatché, M.-C., Courson, R., Loubinoux, I., Vieu, C., Malaquin, L. Two-photon
lithography and microscopy of 3D hydrogel scaffolds for neuronal cell growth, Biomed Phys
Eng Express, 2018, 4, 027009.
[116] Marino, A., Tricinci, O., Battaglini, M., Filippeschi, C., Mattoli, V., Sinibaldi, E., Ciofani, G. A
3D real-scale, biomimetic, and biohybrid model of the blood-brain barrier fabricated through
two-photon lithography, Small, 2018, 14, 1702959.
[117] Zheng, Y. C., Zhao, Y. Y., Zheng, M. L., Chen, S. L., Liu, J., Jin, F., Dong, X. Z., Zhao, Z. S.,
Duan, X. M. Cucurbit[7]uril-Carbazole two-photon photoinitiators for the fabrication of
biocompatible three-dimensional hydrogel scaffolds by laser direct writing in aqueous
solutions, ACS Appl Mater Interfaces, 2019, 11, 1782–1789.
[118] Lin, Y., Xu, J. Microstructures fabricated by two-photon polymerization and their remote
manipulation techniques: Toward 3D printing of micromachines, Adv Opt Mater, 2018, 6,
1701359.
[119] Xiong, W., Liu, Y., Jiang, L. J., Zhou, Y. S., Li, D. W., Jiang, L., Silvain, J. F., Lu, Y. F. Laser-
directed assembly of aligned carbon nanotubes in three dimensions for multifunctional
device fabrication, Adv Mater, 2016, 28, 2002–2009.
[120] Staudinger, U., Zyla, G., Krause, B., Janke, A., Fischer, D., Esen, C., Voit, B., Ostendorf,
A. Development of electrically conductive microstructures based on polymer/CNT
nanocomposites via two-photon polymerization, Microelectron Eng, 2017, 179, 48–55.
[121] Nakamura, R., Kinashi, K., Sakai, W., Tsutsumi, N. Fabrication of gold microstructures using
negative photoresists doped with gold ions through two-photon excitation, Phys Chem Chem
Phys, 2016, 18, 17024–17028.
[122] Shukla, S., Vidal, X., Furlani, E. P., Swihart, M. T., Kim, K. T., Yoon, Y. K., Urbas, A., Prasad,
P. N. Subwavelength direct laser patterning of conductive gold nanostructures by
simultaneous photopolymerization and photoreduction, ACS Nano, 2011, 5, 1947–1957.
[123] Blasco, E., Muller, J., Muller, P., Trouillet, V., Schon, M., Scherer, T., Barner-Kowollik, C.,
Wegener, M. Fabrication of conductive 3D gold-containing microstructures via direct laser
writing, Adv Mater, 2016, 28, 3592–3595.
[124] Marino, A., Barsotti, J., de Vito, G., Filippeschi, C., Mazzolai, B., Piazza, V., Labardi, M.,
Mattoli, V., Ciofani, G. Two-photon lithography of 3D nanocomposite piezoelectric scaffolds
for cell stimulation, ACS Appl Mater Interfaces, 2015, 7, 25574–25579.
[125] Beresna, M., Gecevičius, M., Bulgakova, N. M., Kazansky, P. G. Twisting light with
micro-spheres produced by ultrashort light pulses, Opt Express, 2011, 19, 18989.
[126] Wei, H., Amrithanath, A. K., Krishnaswamy, S. 3D printing of micro-optic spiral phase plates
for the generation of optical vortex beams, IEEE Photonics Technol Lett, 2019, 31, 599–602.
[127] Rybin, M., Shishkin, I., Samusev, K., Belov, P., Kivshar, Y., Kiyan, R., Chichkov, B.,
Limonov, M. Band structure of photonic crystals fabricated by two-photon polymerization,
Crystals, 2015, 5, 61–73.
[128] Purtov, J., Rogin, P., Verch, A., Johansen, V. E., Hensel, R. Nanopillar diffraction gratings by
two-photon lithography, Nanomaterials (Basel), 2019, 9, 1495.
[129] Abrashitova, K., Gulkin, D., Safronov, K., Kokareva, N., Antropov, I., Bessonov, V., Fedyanin,
A. Bloch surface wave photonic device fabricated by femtosecond laser polymerisation
technique, Appl Sci, 2018, 8, 63.
[130] Del Pozo, M., Delaney, C., Bastiaansen, C. W. M., Diamond, D., Schenning, A., Florea,
L. Direct laser writing of four-dimensional structural color microactuators using a photonic
photoresist, ACS Nano, 2020, 14, 9832–9839.
Ali Bagheri, Jianyong Jin
Chapter 9
3D printing mediated by photoRAFT
polymerization process
9.1 Introduction
3D printing technology (otherwise known as additive manufacturing) has changed
the world of manufacturing as it offers a programmable pathway for the layer-by-
layer fabrication of customized and on-demand 3D objects tailored to meet the de-
mands of individuals and specific applications [1]. Among the different techniques,
3D printing via photopolymerization that includes stereolithography (SLA), digital
light processing (DLP) and continuous liquid interface production (CLIP) is one of
the most attractive methods due to the limitless innovations that can be provided
by polymer chemistry [2, 3]. This technology has contributed to various fields such as
microfluidics, biomedical devices, soft robotics, medical surgery, tissue engineering,
dentistry and drug delivery [4–6].
The photopolymerization mechanism used in 3D printing is normally based on
radical and cationic polymerizations. The radical polymerization (commonly referred
to as “free radical polymerization”)1 finds favor due to its broad monomer and func-
tionality scope. These mechanisms have proved effective in 3D printing of a wide
range of materials with different functionalities and characteristics [3, 7–10]. How-
ever, the application of an alternative chemistry such as photocontrolled reversible
addition fragmentation chain transfer polymerization (photoRAFT) to 3D printing
can offer additional possibilities for advanced material manufacturing. Indeed,
RAFT polymerization is one of the most straightforward, well-established and ver-
satile reversible deactivation radical polymerization (RDRP) technique. RDRP tech-
niques are typically used for producing polymer chains of controlled molecular
weight, structure and architecture. One of the greatest possibilities provided by
RDRP is the ability to produce polymer materials with dormant functionalities. In
the context of polymer crosslinked networks, these dormant functionalities can
be used to enable numerous potential modifications in a postsynthetic stage such
as self-healing/welding [11, 12], grafting polymer side chains [13], expansion of net-
work structures [12, 14], biofunctionalization [15] and spatial differentiation [16].

1 The International Union of Pure and Applied Chemistry recommends adjective “free” not to be used
to describe radical polymerization.

Ali Bagheri, School of Science and Technology, The University of New England, Armidale, Australia
Jianyong Jin, School of Chemical Sciences, The University of Auckland, Auckland, New Zealand

https://doi.org/10.1515/9783110570588-009
296 Ali Bagheri, Jianyong Jin

Moreover, some of RDRP systems are oxygen-tolerant, a characteristic that is re-

quired for conducting fully open-to-air 3D printing processes [17–26].
In the context of 3D materials with transformability features, 4D printing (fourth
dimension being time) concept has been developed which enables changes in shapes,
sizes and properties of 3D printed materials in response to external stimuli such as
temperature, water, pH, light, etc. [27–34]. This ability is normally realized by integra-
tion of stimuli responsive functionalities into the resin formulations which can be-
come part of the printed materials [32]. Integration of light-responsive functional
groups such as RAFT agents within the structure of 3D printed materials – which is
the focus of this chapter – can be also considered as a subclass of 4D printing. How-
ever, the main difference between conventional 4D printing cases and introduction of
RAFT agents into the resin formulation is that RAFT agents can participate in mediat-
ing the photoreaction process. This means that RAFT agents can have two roles: i)
mediating the photopolymerization (printing process) and ii) serving as reactivatable
specie to enable postprinting monomer addition onto the surface or within the struc-
ture of an already printed object via a subsequent RAFT process. Recently, the first
proof of concept of photoRAFT-mediated 3D printing of materials capable of post-
printing modification has been demonstrated [35–37].
In this chapter, we first provide an overview of the conventional photopolymeriza-
tion-based 3D printing techniques. We then discuss the mechanisms behind (photo)
RAFT polymerization alongside the possibilities that this technique has to offer to the
crosslinked networks, particularly to the 3D printing technology. The recent key works
on the application of photoRAFT in 3D printing have also been highlighted. The major
challenges that restrict scaling and translation of photoRAFT facilitated 3D printing
into industrial settings are also discussed.

9.2 Conventional photopolymerization techniques

used in 3D printing
Three main techniques are typically used in 3D printing via photopolymerization.
They are stereolithography (SLA) [6, 38–41], digital light processing (DLP) [42–54]
and continuous liquid interface production (CLIP) [55, 56]. These techniques are
fundamentally based on crosslinking of liquid monomer/oligomers, which pro-
ceed via radical or cationic polymerization in the presence of photoinitiators. The
most commonly used photocurable formulations contain (meth)acrylate mono-
mers/oligomers that can be cured via radical polymerization. The mechanism can
be broken into three stages: initiation, propagation and termination. In the initiation
stage, photocleavable single molecules, known as type I photoinitiators (e.g. benzil
ketals and phosphine oxide containing compounds), are typically exploited for
radical generation under exposure to light. These photoinitiators have high molar
 Chapter 9 3D printing mediated by photoRAFT polymerization process 297

extinction coefficients at short wavelengths (e.g. UV light) [7, 8]. Type II photoinitia-
tors which are based on the interaction of an uncleavable sensitizer and a coinitiator
can be also used for radical generation. We refer the readers to other reviews for
more information about the photoinitiator structures and the mechanisms by
which reactive radical species are formed [7, 8, 57]. The recent advancements on
the novel one-photon and two-photon photoinitiators are also demonstrated in Chap-
ter 1 and Chapter 2. In the propagation stage (photocrosslinking), (meth)acrylate
monomer/oligomers containing multifunctional monomers such as poly(ethylene
glycol)diacrylate (PEGDA) [44, 58, 59], urethane dimethacrylate [60, 61], triethylene
glycol dimethacrylate [62–65], bisphenol A glycidyl methacrylate [62–65], trimethylol-
propane triacrylate [55, 56, 60], and bisphenol A ethoxylate diacrylate [41] can be
used. Inherently, in radical polymerization, the rate of initiation is relatively slower
than propagation and the termination reactions are mobility-restricted. This results
in a high kinetic chain length and, ultimately, the formation of networks with hetero-
geneity and thus, high brittleness [66, 67]. It has been demonstrated that the use of
addition fragmentation chain transfer (AFCT) agents in the resin formulations reduces
the kinetic chain length and therefore delays the gel point to higher monomer conver-
sion. This results in 3D printing of more uniform networks with reduced shrinkage
stress and improved toughness [68–70].
It is known that oxygen can inhibit the radical polymerization of (meth)acrylate
systems by quenching the excited-state photoinitiator and/or forming a peroxide,
upon interaction with propagating radical species [71, 72]. Tertiary amines or triphe-
nylphosphine have been exploited as additives in resin formulations to minimize the
oxygen inhibition in 3D systems. In addition to the (meth)acrylate systems, thiol-ene
/yne chemistry has also been used in 3D resin formulations [67, 73–76]. The step-
growth mechanism dictating the thiol-ene systems delays the gelation point to a
higher monomer conversion and, therefore, offers lower shrinkage stress of the 3D
printed materials as compared to the (meth)acrylate-based systems [77]. Thiol-ene/
yne systems also offer higher biocompatibility [76] that can be used in 3D fabrication
of biocompatible and biodegradable hydrogel constructs [78, 79]. Thiol-yne chemistry
provides higher glass transition and higher modulus as compared to the thiol-ene-
derived materials. This characteristic is mainly attributed to the vinyl sulfide as the
reaction intermediate capable of undergoing a second addition with excess thiol [76,
80, 81]. For instance, materials printed using the tricyclo [5.2.1.02,6] decane-4,8-
dimethanol dibut-3-yn-1-yl carbonate displayed high strength and lower cytotoxicity
than their corresponding meth(acrylates) formulations [76]. Cationic polymerization
is another type of chemistry used in 3D applications which is typically based on ring
opening photopolymerization of epoxides [10, 65, 82]. In all the systems described
here, UV or visible light-sensitive initiators are commonly used to generate reactive
species to mediate radical or cationic photopolymerization for 3D applications [8, 57,
83, 84]. Although the conventional photopolymerization techniques have proved
highly effective for 3D printing of a wide range of materials, application of an
298 Ali Bagheri, Jianyong Jin

alternative chemistry such as photoRAFT to 3D printing can add a new dimension to

the current technologies.

9.3 Fundamental aspects of RAFT polymerization

and its mechanistic progression
Before discussing the application of photoRAFT to polymer-crosslinked networks
and 3D printing, we provide an overview of the mechanisms of RAFT polymeriza-
tion. RAFT process is a family of RDRP reactions [12, 85–89] discovered in the 1990s
that has become increasingly popular as it can enable controlled synthesis of well-
defined polymers with high chemical fidelity [90]. RAFT polymerization has found
its application in different fields due to its simplicity of implementation as well as
the availability of a wide range of compatible reagents. The mechanism of RAFT
process presented in Figure 9.1(a) shows the RAFT equilibria as an additional step
to the main stages involved in a radical polymerization (e.g. initiation, propagation
and termination) [90]. In RAFT polymerization, propagating radical (P•m) is pro-
duced by radical addition to the monomers (step i). This propagating radical is then
added to thiocarbonylthio RAFT agents followed by a chain transfer reaction (frag-
mentation of the intermediate radical) to generate a polymeric thiocarbonylthio
compound [PmSC(Z) = S] and a new initiating R• radical (step ii). This new radical is
capable of forming a new propagating radical, P•n (step iii), which is capable of enter-
ing into an equilibrium between the active P•m and P•n species (polymeric transfer
agents) and dormant thiocarbonylthio compounds via reversible addition fragmenta-
tion reactions (step ii and iv). In an effective RAFT process, the rate of propagation is
lower than that of the addition/fragmentation equilibrium (reversible chain trans-
fer), which maintains the majority of chains in a dormant form and, therefore, en-
ables all the propagating chains to grow at equal probability; making it possible
to produce linear polymers with narrow polydispersity [68]. More critically, RAFT
functionality remains at the chain-end or within the polymer backbone (depending
on the structure of the RAFT agent used) that can be further used for postpolymeriza-
tion reactions (e.g. chain extension to form di or triblock copolymers) [68].
The initiation step in RAFT polymerization was traditionally based on the decom-
position of thermal initiators [91]. Although thermally initiated systems are broadly
studied, such thermally labile initiators are typically hazardous and in the polymeri-
zation process, the initiator fragment can be attached to a fraction of the polymer
chain-ends, which compromises the chain-end fidelity of the polymer products. As
RAFT process developed over the years, alternative routes to generate radicals and
activate RAFT polymerization have been developed using ultrasound, enzymes, elec-
trochemical, light, etc. [94]. In particular, photoactivation pathway enables high de-
grees of spatial and temporal control on polymerization at low temperatures and it
 Chapter 9 3D printing mediated by photoRAFT polymerization process 299

Figure 9.1: (a) Traditional RAFT polymerization activated via radical addition [91]. Radical can be
formed by different stimuli. Note that the termination process is not shown in this scheme, (b) A
reversible termination polymerization [92]., (c) Photoiniferter polymerization [93], and (d)
Photoinduced electron/energy-transfer reversible addition–fragmentation chain-transfer (PET-RAFT)
polymerization [71]. P: polymer chain, Pn•: propagating radical species, Z: reactivity-modifying
group, M: monomer and PC: photocatalyst.

also facilitates synthesis of polymer chains with high chain-end fidelity [85–87].
Photoactivation can be either through direct activation of RAFT agents (known as
photoiniferter mechanism) or indirectly using chromophores such as photocatalysts –
known as photoinduced electron or energy transfer RAFT (PET-RAFT).
Before the first report of RAFT polymerization, Otsu and coworkers introduced the
concept of photoinduced initiator-transfer agent terminators (photoiniferters) based on
300 Ali Bagheri, Jianyong Jin

sulphur-containing compounds to synthesize polymers via a degenerative chain trans-

fer (Figure 9.1(a)) and reversible termination mechanism (Figure 9.1(b)) [93]. Following
the pioneering works of Otsu, various thiocarbonylthio RAFT agents (Figure 9.2) were
explored as photoiniferters to control the radical polymerizations. In early systems, UV
light was utilized to induce a thiocarbonyl π → π* transition, resulting in C–S bond
cleavage, to produce an active carbon-centered radical to control the radical polymeri-
zation [95, 96]. The UV-mediated systems showed relatively poor control over the mo-
lecular distribution of polymer chains, especially at high monomer conversions, which
was mainly attributed to irreversible photolytic degradation of the fragmented RAFT
agents under UV exposure (Figure 9.1(c)) [97]. To suppress the degradation of RAFT
agents, visible light has been recently employed to induce n → π* transitions, resulting
in C–S bond cleavage and, thus, radical generation to activate radical polymerization
via two simultaneous pathways: i) reversible termination and ii) radical activation of a
RAFT-type degenerative chain transfer process following photolysis of the thiocarbo-
nylthio compounds (Figure 9.1(c)) [93, 98–101]. It should be mentioned that not all the
RAFT agents are capable of undergoing photolysis under visible light. Specific trithio-
carbonates (e.g. possessing tertiary R groups) can be activated under visible light with-
out the presence of external initiators. Experiments undertaken by Davis, Rizzardo and
coworkers elucidated that the degenerative chain transfer (e.g. RAFT process) is the

Figure 9.2: Typical examples of thiocarbonylthio compounds used in photoRAFT polymerization

systems. Some of these thiocarbonylthio compounds can be used as photoiniferters while some can
be used as RAFT agents in PET-RAFT systems. CDTPA: 4-cyano-4-[(dodecylsulfanylthiocarbonyl)
sulfanyl] pentanoic acid, BSTP: 3-benzylsulfanyl-thiocarbonylthiosulfanyl propionic acid, BTPA:
(2-(nbutyltrithiocarbonate)-propionic acid, DBTTC: dibenzyl trithiocarbonate, DDMAT: S-1-Dodecyl-S′-
(α, α′-dimethyl-α′′-acetic acid) trithiocarbonate, CPD-TTC: 2-cyano-2-propyl dodecyl trithiocarbonate,
CMP: 2-(1-Carboxy-1-methylethylsulfanylthiocarbonylsulfanyl)-2-methylpropionic acid, CPADB:
4-cyanopentanoic acid dithiobenzoate, and CDB: 2-phenyl-2-propyl benzodithioate.
 Chapter 9 3D printing mediated by photoRAFT polymerization process 301

main process that provides control over the polymerization, while the extent to which
the mechanistic pathway of reversible termination occurs is unclear [92].
Photoactivation of thiocarbonylthio compounds can be also realized indirectly
using external redox-active catalytic species. Excited photoredox catalysts can interact
with the RAFT agents and control the activation-deactivation equilibrium of RAFT
polymerization via electron/energy transfer cyclic processes. This process is known
as photoinduced electron or energy transfer RAFT (PET-RAFT) (Figure 9.1(d)) [71,
102–105]. Compared to the thiocarbonylthio iniferters, photoredox catalysts have
better photochemical properties with relatively long-lived excited states and suitable
redox potentials. Therefore, PET-RAFT systems offer faster polymerization rates as
compared to the photoiniferter-mediated polymerization [85, 106]. It should be
pointed out that even in the presence of photoredox catalysts (especially when
light sources of shorter wavelengths are used), thiocarbonylthio compounds can
undergo photolysis and, therefore, multiple mechanisms of activation are likely to
happen simultaneously [107]. Having said that, the dictating mechanism is highly
dependent upon the irradiation wavelength and the reagents used. Thus far, a
wide range of photocatalysts with strong absorption in the visible and NIR range
have proved compatible with PET-RAFT polymerization, which opened up new
possibilities in polymer synthesis [71, 108]. More importantly, various photoredox
catalysts (Figure 9.3) such as Ir(ppy)3 [71], Ru(bpy)3Cl2 [109], eosin Y (EY) [103,
107], pheophorbide a (PheoA) [108], and zinc tetraphenylporphine (ZnTPP) [12,
87, 110] can provide oxygen-tolerant systems via different mechanisms that are
well studied in the literature [22, 94, 109, 111].
While the potential application of photoRAFT technique is not covered in this
chapter, it is worth mentioning that this technique has been exploited in a variety
of contexts including but not limited to the synthesis of well-defined block copoly-
mers and nano/micro size polymeric particles, surface modification of diverse mate-
rials, sequence-defined polymers, chemically and architecturally diverse polymers
(e.g. self-assemblies, brushes, stars and multi-blocks), etc. [94, 112]. In the context
of polymer crosslinked networks, RAFT polymerization has the ability to reversibly
deactivate the propagating radial species, which enables improved control over
polymer chain growth, and therefore making it possible to relatively tune the net-
work uniformity [91]. However, using RAFT polymerization does not allow direct
control over the distance between the crosslinking points in covalently crosslinked
networks, or direct control of the pore sizes [113].
 302
Ali Bagheri, Jianyong Jin

Figure 9.3: Typical examples of chromophores used as photocatalysts in PET-RAFT polymerization; PTH: 10-
phenylphenothiazine, Ru(bpy)32+: tris(2,2′-bipyridine) ruthenium(II), EY: eosin Y, ZnTPP: zinc tetraphenylporphine,
PheoA: pheophorbide a, AIPc: aluminum phthalocyanine, and Ir(ppy)3: tris-phenylpyridine cyclometalated fac-Ir(ppy)3.
 Chapter 9 3D printing mediated by photoRAFT polymerization process 303

9.4 Use of RAFT polymerization in the synthesis

of polymeric crosslinked networks
Before discussing the application of photoRAFT in 3D printing, we provide a general
overview of the polymeric crosslinked networks that contain RAFT agents within their
structures [1, 28, 89, 114]. As we discussed in section 9.3, dynamic equilibrium between
the dormant and active species is the foundation of RAFT polymerization, which
is facilitated by the RAFT agents [115, 116]. The reversible bond exchange between the
trithiocarbonate (TTC) units can enable crosslinked polymer networks to undergo self-
healing via reshuffling of reversible covalent bonds (Figure 9.4(a)) [115]. For instance,

(a) •
UV S • • S S •
S S S R1 R1 R2
R1 R1 R1
Reshuffling reaction: S S S
Degenerative exchange between
TTCs catalyzed by radical S S
R2 R2 R2 R1
S S S S

(b) Photoredox catalyzed growth of cross-

linked polymer network
Propagation
i) Recombine & SET
Cleaved network
PTH in solution strand with stable
TTC anion end +
R Cleaved
Blue S S network
LED Network Network⊝ Network + • Network strand with
light S S S S
+ propagating
Network strand with •⊕ RAFT end
TTC iniferter Process
PTH radical cation
Network Network
PTH* in solution SET & fragment
ii)
Tetra-DBCO-PEG
Method A
M (NIPAAM ~ )
N H H
N N
O O
O SPAAC O
n
O MeCN PTH, MeCN
+
S LED (410 nm)
N3 O S S O N3
Gel I
O O
Parent PEG-TTC network
Bis-N3-TTC Daughter network (NIPAAM added)

Figure 9.4: (a) An illustration of how the TTCs undergo degenerative exchange reaction and
enable material self-healing under UV light exposure, (b) Photoredox catalyzed growth (PRCG) of
crosslinked polymer networks. (i and ii) Proposed mechanism of PRCG polymerization using PTH
and a network comprised of strands bearing TTC iniferters. Reproduced with permission from
[89]. Copyright 2017 American Chemical Society. (https://pubs.acs.org/doi/abs/10.1021/acs
centsci.6b00335). Further permissions related to the material excerpted should be directed to
the American Chemical Society.
304 Ali Bagheri, Jianyong Jin

Matyjaszewski and coworkers used UV light to induce homolysis of TTCs (present

within crosslinked networks) and generate carbon radicals, enabling reactions
with other TTCs via degenerative exchange process [11].
In the RAFT process, the thiocarbonylthio groups preserved in the polymer
products can be further used for postpolymerization reactions (e.g. chain extension
to form di or triblock copolymers). In polymer crosslinked networks that are formed
using RAFT agents, postsynthetic modifications can be realized through reacti-
vation of the preserved RAFT functionalities. Depending upon the nature of the RAFT
agents and their molecular structure, the postsynthetic reactions differ. For instance,
when the RAFT functionalities are present at the chain-ends, surface-initiated
polymerization can be obtained. When the preserved functionalities are present
in the core and connect the arms of the RAFT-derived polymer chains, monomer
insertion within the structure of crosslinked networks can be realized [113]. In a
study by Johnson and coworkers, UV light was used to activate TTCs embedded
within a polymer network to facilitate monomer insertion into an already synthe-
sized network, resulting in an increase in the average molecular weights between
the crosslinking points [117].
The field of photopolymerization is moving towards the use of benign visible
lights to avoid the limitations of using high-energy UV light. Some of the main ad-
vantages of using visible light are as follows: Low-energy visible light sources are
eco-friendly with low thermal effects and minimal side reactions. They are also pre-
ferred for bio-related applications [9, 118]. To this end, various types of visible light
sensitive compounds with the ability to initiate photopolymerization in RDRP sys-
tems [85, 86, 106, 119–121] and in 3D printing [1, 9, 10, 45, 65, 76, 122] have been
investigated. It is worth mentioning that in the context of layer-by-layer 3D printing
process, higher wavelength light sources can penetrate deeper and offer higher 3D
printing speed. For example, Matyjaszewski and coworkers demonstrated that green
and blue visible light can be used to activate the TTCs present within the crosslinked
networks to enable different postsynthetic modification pathways such as network ex-
pansion or surface modification [14]. In a similar study, Bagheri, Jin and coworkers re-
ported the synthesis of photoexpandable/transformable-polymer networks (PET-PNs)
using photoiniferter polymerization [12]. In their approach, a symmetric DBTTC RAFT
agent was activated by blue LED light to mediate inferter-based radical polymeri-
zation to fabricate PET-PNs. The preserved DBTTC groups within the structure of
networks were reactivated (in a second photoiniferter process) to facilitate the addi-
tion of new monomers within or onto the surface of pristine networks [12]. Even
though the addition of monomers into the PET-PNs was confirmed by an increase in
the mass and swelling ratio of the modified networks, the uniformity of the photo-
growth process was not controlled. This was explained to be partly due to the use of
conventional crosslinkers and limited accessibility/reactivity of the TTCs within the
network [12].
 Chapter 9 3D printing mediated by photoRAFT polymerization process 305

Instead of photoiniferter-derived polymerization, photoredox catalyzed RAFT po-

lymerization (commonly known as PET-RAFT polymerization) [71, 102–105] can be
also used in the context of crosslinked networks [123]. An early example was the
work by Johnson and coworkers in which a PTH photocatalyst was excited under
blue LED light exposure to interact with the TTC units embedded within a crosslinked
network and, therefore, mediate a RAFT polymerization for insertion of new mono-
mers into an already synthesized network (Figure 9.4(b)) [89]. Inspired by these ad-
vancements, Bagheri, Jin and coworkers reported the synthesis of PET-PNs using
ZnTPP as a photoredox catalyst in the presence of DBTTC RAFT agents and a diacry-
late crosslinker. In the postsynthesis stage, the preserved TTC functionalities found
within the networks were reactivated to enable addition of new monomers onto the
surface and within the structure of an existing network [12]. One of the ultimate goals
of the studies was to implement these systems in a practical 3D printing system to ren-
der postprinting modification a reality. This area of research which was historically
unexplored (due to the slow polymerization rate and oxygen sensitivity of RDRP
techniques) has been recently comprehended by the pioneering works of Bagheri and
Jin in collaboration with Boyer’s group, which are elaborated in the following section.

9.5 Use of photo RAFT polymerization in 3D printing

Polymer networks have traditionally been synthesized using solution or bulk polymeri-
zation, while the emergence of 3D printing technology enabled an alternative way for
on-demand production of polymer networks with complex structures in streamlining
the additive manufacturing processes [124, 125]. As elaborated in Section 9.2, the poly-
mer chemistry used in photopolymerization-based 3D printing is typically based on
radical and/or cationic polymerization [47, 126]. The use of an alternative chemistry,
for example photoRAFT, can broaden the possible scope of 3D technology. Perhaps
one of the opportunities is postprinting modification facilitated by (re)activation of
RAFT functionalities integrated within the structure of 3D printed materials.
The first example of photoiniferter facilitated 3D printing was reported by Bagheri
and Jin in collaboration with Boyer [35]. A formulation containing TTC units (e.g.
CDTPA or DBTTC) and a diacrylate monomer (e.g. PEGDA) was prepared in the com-
plete absence of exogenous initiators/catalysts and solvent (Figure 9.5(a) i and ii). This
formulation was used in a layer-by-layer photopolymerization process facilitated by a
modified DLP 3D printer equipped with a photomask and LED lights (λ max = 405 nm,
1.8 mW/cm2). Upon exposure to light, TTCs acted as photoiniferters and mediated the
photopolymerization of diacrylate monomers. In a postprinting stage, the preserved
TTC species present in the 3D printed networks were reactivated to enable monomer
addition (e.g. 1-pyrenemethyl methacrylate (PyMA) or n-butyl acrylate (BA)) within or
on the surface of already printed materials [35]. As can be seen from Figure 9.6(a), the
306 Ali Bagheri, Jianyong Jin

(a) i) ii) (b)

S CN R3N
O
OH O

oc FT
EY*

s
S S O

RA
es
10 n
CDTPA O PEGDA O R3N•+
PET M

Pr
Or 250
S O •
Pn
S S O EY•– S +
DBTTC BA ⊝
S S–Z

O•
iii) –
2
COO– EY R3N•+
Visible light O2
Br Br N
– S
O O O TEA
Br Br Pn–S S–Z R3N
EY
Modified DLP
(c) EY absorbance (d) EY absorbance
Green LED emission
(e) printer
Blue LED emission

Cured
Cured

Resin formulation
Mask
400 450 500 550 600 400 450 500 550 600 650 Visible light
Wavelength (nm) Wavelength (nm)

(f) (g) (h)

0.296 mm

500 μm 100 μm

Figure 9.5: (a) Chemical structures of components in the formulation used for 3D printing: i) CDTPA and
DBTTC, ii) PEGDA (Mn = 250 g/mol) and BA monomer, and iii) EY and TEA. For the photoiniferter-based
3D printing, a formulation containing i and ii was used, while for the PET-RAFT based 3D printing, EY
and TEA (iii) were added to the formulation, (b) Proposed photopolymerization mechanism under
visible light irradiation. This mechanism has been previously reported in both solution [86] and bulk
[129] RDRP for preparing linear polymers [107], (c) UV-vis absorption spectrum of EY and the emission
spectrum of the in house build blue LED light source of 3D printer, (d) UV-vis absorption spectrum of EY
and the emission spectrum of the in house build green LED light source of 3D printer, (e) Schematic of
3D printing process using a modified bottom-up DLP printer equipped with a photomask and blue
(λ max = 483 nm, 4.16 mW/cm2) or green (λ max = 532 nm, 0.48 mW/cm2) LED lights, at room
temperature and fully open to air, (f) An optical image and a microscope image of a 3D object printed
using PET formulation, and (g-h) Representative SEM images of the printed objects. Reproduced with
permission from [36]. Copyright 2020 American Chemical Society.

polyPyMA (PPyMA)-modified network exhibited excimer emission of pyrene moieties

under 365 nm UV light exposure. The optical image of the PPyMA-modified disc taken
under UV light exposure, exhibited stronger excimer emission from the outer regions
as compared to the central areas of the disc, suggesting a bigger block of PPyMA
added to the areas where TTCs were possibly more accessible [12, 127]. It should
 Chapter 9 3D printing mediated by photoRAFT polymerization process 307

Figure 9.6: (a) Optical images of an initially 3D printed network and its subsequent modified
network after PyMA monomer addition (image taken under 365 nm UV light exposure).
Reproduced with permission from [35]. Copyright 2020 Royal Society of Chemistry. (b) Water
contact angle measurements of a 3D printed network with high surface wettability and its
subsequent modified network with decreased surface wettability after BA monomer addition.
Reproduced with permission from [37]. Copyright 2019 John Wiley and Sons.

be mentioned that postmanufacturing monomer insertion within the structure of

highly crosslinked networks, especially those that are formed using symmetrical
RAFT, are complex and require further in-depth exploration [113]. Moreover, fac-
tors such as crosslinking density, (re)activatability of the preserved TTC species,
the distribution of the TTCs within the network, and the uniformity of light expo-
sure/penetration can affect the postprinting modification reactions. The printing
speed of the photoiniferter-based formulation was significantly slower than the
systems based on conventional formulations that proceed via free radical poly-
merization using type I or type II photoinitiators [1, 126]. This was partly due to the
slow activation rate of TTCs (via photolysis) as well as chain transfer reactions
that result in slower propagation rates [91]. It is known that carbon-centered radi-
cals can react with molecular oxygen to form peroxy radical and hydroperoxides
that are not reactive for reinitiating polymerization [17–20, 71, 128]. To avoid oxy-
gen inhibition, the 3D printing process was conducted in an inert atmosphere by
the physical displacement of oxygen from the resin vat using a glovebox [35].
Oxygen sensitivity makes conducting a 3D printing process challenging at a
large scale where displacement of oxygen is demanding without increased manufactur-
ing costs. Therefore, translation of RAFT-based 3D printing into industrial setting
requires the use of an oxygen-tolerant system [130]. Thus far, various chemical
approaches have been reported to scrub oxygen from the polymerization reaction,
for instance, polymerizing through oxygen, [20–22] enzyme-mediated deoxygenation
[23, 24] and the consumption of molecular oxygen via a PET process initiated from
photoredox catalysts [25, 26, 111, 131]. Organic dyes such as EY have also been used
as a PET catalyst for preparing linear polymers in the presence of oxygen [86, 103,
308 Ali Bagheri, Jianyong Jin

107, 129, 132]. To realize a fully open 3D printing process, Bagheri et al. complemented
their initial photoiniferter-based formulation (which was proceeded via photolysis of
RAFT agents) with the addition of a EY photocatalyst and a sacrificial triethylamine
reducing agent (Figure 9.5(a) iii). The photopolymerization of a diacrylate monomer
(e.g. PEGDA), proceeded, in principle, via a PET pathway, as shown in Figure 9.5(b)
[36]. Using this formulation, the active molecular oxygen can be consumed to form
inactive superoxide anions by electron transfer from an eosin-radical anion or anion
RAFT species [17, 86, 133]. The layer-by-layer 3D printing process was carried out in
a completely open-to-air environment using a modified DLP printer (with a photo-
mask) equipped with blue (λmax = 483 nm, 4.16 mW/cm2) or green (λmax = 532 nm,
0.48 mW/cm2) LED lights (Figure 9.5(c–e)) [36]. The use of green LED light showed
higher 3D printing build speed compared to blue LED-induced printing, which
was due to the greater absorbance-emission overlap between EY and green LED
emission as well as the higher penetration depth of the green light [36]. To demon-
strate that the photopolymerization proceeded via a layer-by-layer process, [35]
scanning electron microscopy (SEM) analysis was used to obtain images of the
printed object. The analysis confirmed high accuracy in layer uniformity and
thickness that are in agreement with the predefined values using slicing software
(Figure 9.5(f–h)) [36]. As the major motivation behind using RAFT-based systems in
3D printing was to produce materials containing dormant reactivatable species, post-
printing modification was demonstrated by the addition of BA monomers from the
preserved and accessible TTC units to change the surface hydrophilicity of the
printed object [36]. At the same time, Boyer, Corrigan and colleagues also exploited
an oxygen-tolerant PET-RAFT system based on a water soluble Erythrosin B photoca-
talyst and a triethanolamine reducing agent, which facilitated 3D printing in aqueous
solutions. The preserved TTC units were then reactivated in a postprinting stage to pro-
duce materials with different functionalities, such as materials with different surface
wettability (Figure 9.6(b)) [37].

9.6 Conclusions and perspectives

3D printing via photopolymerization is typically conducted using radical, cationic
and/or thiol-ene/yne polymerization. These mechanisms have enabled 3D printing
of materials with a wide range of functionalities and applications. However, the use
of an alternative chemistry based on RAFT polymerization can add a new dimension
to the existing techniques. In particular, integration of RAFT functionalities within
the structure of (3D) crosslinked networks can provide different post-manufacturing
possibilities that is not achievable using conventional formulations. Having said that,
although the application of RAFT in 3D printing technology represents a noteworthy
progress, its development has been constrained due to the slow polymerization rate
 Chapter 9 3D printing mediated by photoRAFT polymerization process 309

and the oxygen sensitivity of the RAFT systems. Further success in the application of
photoRAFT to 3D printing requires the following essential challenges to be overcome:
(i) photopolymerization must achieve fast kinetics at room temperature; (ii) the pres-
ence of a small amount of oxygen must not inhibit the reaction. Moreover, in the
field of 3D bioprinting, the activation wavelength required to mediate the photo-
polymerization must not harm biosensitive materials or degrade the reactants – this
means that developing printable formulations that are responsive to longer wave-
lengths is highly demanded. We envisage that photoRAFT will open up new opportu-
nities in the field of 3D printing for fabrication of advanced functional materials.

References
[1] Bagheri, A., Jin, J. Photopolymerization in 3D printing, ACS Appl Polym Mater, 2019, 1,
593–611.
[2] Layani, M., Wang, X., Magdassi, S. Novel materials for 3D printing by photopolymerization,
Adv Mater, 2018, 30, 1–7.
[3] Zhang, J., Xiao, P. 3D printing of photopolymers, Polym Chem, Royal Society of Chemistry,
2018, 9, 1530–1540.
[4] Wang, M. O., Vorwald, C. E., Dreher, M. L., Mott, E. J., Cheng, M. H., Cinar, A., et al.
Evaluating 3D-printed biomaterials as scaffolds for vascularized bone tissue engineering,
Adv Mater, 2014, 27, 138–144.
[5] Rusling, J. F. Developing microfluidic sensing devices using 3D printing, ACS Sensors, 2018,
3, 522–526.
[6] Zorlutuna, P., Jeong, J. H., Kong, H., Bashir, R. Stereolithography-based hydrogel
microenvironments to examine cellular interactions, Adv Funct Mater, 2011, 21, 3642–3651.
[7] Ligon, S. C., Liska, R., Stampfl, J., Gurr, M., Mülhaupt, R. Polymers for 3D printing and
customized additive manufacturing, Chem Rev, 2017, 117, 10212–10290.
[8] Jasinski, F., Zetterlund, P. B., Braun, A. M., Chemtob, A. Photopolymerization in dispersed
systems, Prog Polym Sci, Elsevier Ltd, 2018, 84, 47–88.
[9] Zhang, J., Dumur, F., Xiao, P., Graff, B., Bardelang, D., Gigmes, D., et al. Structure design of
naphthalimide derivatives: Toward versatile photoinitiators for Near-UV/Visible LEDs, 3D
printing, and water-soluble photoinitiating systems, Macromolecules, 2015, 48, 2054–2063.
[10] Zhang, J., Dumur, F., Xiao, P., Graff, B., Gigmes, D., Pierre Fouassier, J., et al.
Aminothiazonaphthalic anhydride derivatives as photoinitiators for violet/blue LED-Induced
cationic and radical photopolymerizations and 3D-Printing resins, J Polym Sci Part A Polym
Chem, 2016, 54, 1189–1196.
[11] Amamoto, Y., Kamada, J., Otsuka, H., Takahara, A., Matyjaszewski, K. Repeatable
photoinduced self-healing of covalently cross-linked polymers through reshuffling of
trithiocarbonate units, Angew Chemie – Int Ed, 2011, 50, 1660–1663.
[12] Bagheri, A., Bainbridge, C., Jin, J. Visible light-induced transformation of polymer networks,
ACS Appl Polym Mater, 2019, 1, 1896–1904.
[13] Cuthbert, J., Zhang, T., Biswas, S., Olszewski, M., Shanmugam, S., Fu, T., et al. Structurally
tailored and engineered macromolecular (STEM) gels as soft elastomers and hard/soft
interfaces, Macromolecules, 2018, 51, 9184–9191.
310 Ali Bagheri, Jianyong Jin

[14] Shanmugam, S., Cuthbert, J., Flum, J., Fantin, M., Boyer, C., Kowalewski, T., et al.
Transformation of gels: Via catalyst-free selective RAFT photoactivation, Polym Chem, Royal
Society of Chemistry, 2019, 10, 2477–2483.
[15] He, H., Averick, S., Mandal, P., Ding, H., Li, S., Gelb, J., et al. Multifunctional hydrogels with
reversible 3D ordered macroporous structures, Adv Sci, 2015, 2, 1–6.
[16] Cuthbert, J., Beziau, A., Gottlieb, E., Fu, L., Yuan, R., Balazs, A. C., et al. Transformable
materials: Structurally tailored and engineered macromolecular (STEM) gels by controlled
radical polymerization, Macromolecules, American Chemical Society, 2018, 51, 3808–3817.
[17] Ligon, S. C., Husár, B., Wutzel, H., Holman, R., Liska, R. Strategies to reduce oxygen
inhibition in photoinduced polymerization, Chem Rev, 2014, 114, 577–589.
[18] Wilson, O. R., Magenau, A. J. D. Oxygen tolerant and room temperature RAFT through
alkylborane initiation, ACS Macro Lett, 2018, 7, 370–375.
[19] Enciso, A. E., Fu, L., Russell, A. J., Matyjaszewski, K. A breathing atom-transfer radical
polymerization: Fully oxygen-tolerant polymerization inspired by aerobic respiration of cells,
Angew Chemie – Int Ed, 2018, 57, 933–936.
[20] Gody, G., Barbey, R., Danial, M., Perrier, S. Ultrafast RAFT polymerization: Multiblock
copolymers within minutes, Polym Chem, Royal Society of Chemistry, 2015, 6, 1502–1511.
[21] Reyhani, A., McKenzie, T. G., Ranji-Burachaloo, H., Fu, Q., Qiao, G. G. Fenton-RAFT
polymerization: An “On-Demand” chain-growth method, Chem – A Eur J, 2017, 23,
7221–7226.
[22] Lamb, J. R., Qin, K. P., Johnson, J. A. Visible-light-mediated, additive-free, and open-to-air
controlled radical polymerization of acrylates and acrylamides, Polym Chem, Royal Society of
Chemistry, 2019, 10, 1585–1590.
[23] Chapman, R., Gormley, A. J., Stenzel, M. H., Stevens, M. M. Combinatorial low-volume
synthesis of well-defined polymers by enzyme degassing, Angew Chemie – Int Ed, 2016, 55,
4500–4503.
[24] Oytun, F., Kahveci, M. U., Yagci, Y. Sugar overcomes oxygen inhibition in photoinitiated free
radical polymerization, J Polym Sci Part A Polym Chem, 2013, 51, 1685–1689.
[25] Niu, J., Page, Z. A., Dolinski, N. D., Anastasaki, A., Hsueh, A. T., Soh, H. T., et al. Rapid visible
light-mediated controlled aqueous polymerization with in situ monitoring, ACS Macro Lett,
2017, 6, 1109–1113.
[26] Ren, K., Perez-Mercader, J. Thermoresponsive gels directly obtained: Via visible light-
mediated polymerization-induced self-assembly with oxygen tolerance, Polym Chem, Royal
Society of Chemistry, 2017, 8, 3548–3552.
[27] Lee, J., Kim, H. C., Choi, J. W., Lee, I. H. A review on 3D printed smart devices for 4D printing,
Int J Precis Eng Manuf – Green Technol, 2017, 4, 373–383.
[28] Sydney Gladman, A., Matsumoto, E. A., Nuzzo, R. G., Mahadevan, L., Lewis, J. A. Biomimetic
4D printing, Nat Mater, 2016, 15, 413–418.
[29] Momeni, F., Mehdi, M., Hassani, N. S., Liu, X., Ni, J. A review of 4D printing, Mater Des,
Elsevier Ltd, 2017, 122, 42–79.
[30] Yang, H., Leow, W. R., Wang, T., Wang, J., Yu, J., He, K., et al. 3D printed photoresponsive
devices based on shape memory composites, Adv Mater, 2017, 29, 1701627.
[31] Kotikian, A., Truby, R. L., Boley, J. W., White, T. J., Lewis, J. A. 3D printing of liquid crystal
elastomeric actuators with spatially programed nematic order, Adv Mater, 2018, 30, 1–6.
[32] Dutta, S., Cohn, D. Temperature and pH responsive 3D printed scaffolds, J Mater Chem B,
Royal Society of Chemistry, 2017, 5, 9514–9521.
[33] Roppolo, I., Chiappone, A., Angelini, A., Stassi, S., Frascella, F., Pirri, C. F., et al. 3D printable
light-responsive polymers, Mater Horizons, Royal Society of Chemistry, 2017, 4, 396–401.
 Chapter 9 3D printing mediated by photoRAFT polymerization process 311

[34] Zhao, Z., Kuang, X., Yuan, C., Qi, H. J., Fang, D. Hydrophilic/hydrophobic composite shape-
shifting structures, ACS Appl Mater Interfaces, American Chemical Society, 2018, 10,
19932–19939.
[35] Bagheri, A., Engel, K. E., Bainbridge, C. W. A., Xu, J., Boyer, C., Jin, J. 3D printing of polymeric
materials based on photo-RAFT polymerization, Polym Chem, Royal Society of Chemistry,
2020, 11, 641–647.
[36] Bagheri, A., Bainbridge, C. W. A., Engel, K. E., Qiao, G. G., Xu, J., Boyer, C., et al. Oxygen
tolerant PET-RAFT Facilitated 3D printing of polymeric materials under visible LEDs, ACS Appl
Polym Mater, 2020, 2, 782–790.
[37] Zhang, Z., Corrigan, N., Bagheri, A., Jin, J., Boyer, C., Versatile, A. 3D and 4D printing system
through photocontrolled RAFT polymerization, Angew Chemie – Int Ed, 2019, 58,
17954–17963.
[38] Hull, C. W. Apparatus for production of three-dimensional objects by stereolithography.
U.S. Patent 4575330. 1986. US4575330A.
[39] Elomaa, L., Pan, C. C., Shanjani, Y., Malkovskiy, A., Seppälä, J. V., Yang, Y. Three-dimensional
fabrication of cell-laden biodegradable poly(ethylene glycol-co-depsipeptide) hydrogels by
visible light stereolithography, J Mater Chem B, 2015, 3, 8348–8358.
[40] Wang, X., Jiang, M., Zhou, Z., Gou, J., Hui, D. 3D printing of polymer matrix composites: A
review and prospective, Compos Part B Eng, Elsevier Ltd, 2017, 110, 442–458.
[41] Credi, C., Fiorese, A., Tironi, M., Bernasconi, R., Magagnin, L., Levi, M., et al. 3D printing of
cantilever-type microstructures by stereolithography of ferromagnetic photopolymers, ACS
Appl Mater Interfaces, 2016, 8, 26332–26342.
[42] Rossi, S., Puglisi, A., Benaglia, M. Additive manufacturing technologies: 3D printing in
organic synthesis, ChemCatChem, 2018, 10, 1512–1525.
[43] Wu, G. H., Hsu, S. H. Review: Polymeric-based 3D printing for tissue engineering, J Med Biol
Eng, Springer Berlin Heidelberg, 2015, 35, 285–292.
[44] Chiappone, A., Fantino, E., Roppolo, I., Lorusso, M., Manfredi, D., Fino, P., et al. 3D printed
PEG-based hybrid nanocomposites obtained by Sol–Gel technique, ACS Appl Mater
Interfaces, 2016, 8, 5627–5633.
[45] Wang, J., Stanic, S., Altun, A. A., Schwentenwein, M., Dietliker, K., Jin, L., et al. A highly
efficient waterborne photoinitiator for visible-light-induced three-dimensional printing of
hydrogels, Chem Commun, 2018, 54, 920–923.
[46] Dilla, R. A., Motta, C. M. M., Snyder, S. R., Wilson, J. A., Wesdemiotis, C.,
Becker, M. L. Synthesis and 3D printing of PEG-Poly(propylene fumarate) diblock and triblock
copolymer hydrogels, ACS Macro Lett, 2018, 7, 1254–1260.
[47] Zhu, W., Qu, X., Zhu, J., Ma, X., Patel, S., Liu, J., et al. Direct 3D bioprinting of prevascularized
tissue constructs with complex microarchitecture, Biomaterials, Elsevier Ltd, 2017, 124,
106–115.
[48] Soman, P., Chung, P. H., Zhang, A. P., Chen, S. Digital microfabrication of user-defined 3D
microstructures in cell-laden hydrogels, Biotechnol Bioeng, 2013, 110, 3038–3047.
[49] De Leon, A. C., Chen, Q., Palaganas, N. B., Palaganas, J. O., Manapat, J., Advincula, R. C. High
performance polymer nanocomposites for additive manufacturing applications, React Funct
Polym, Elsevier B.V, 2016, 103, 141–155.
[50] Wang, F., Chong, Y., Wang, F. K., He, C. Photopolymer resins for luminescent three-
dimensional printing, J Appl Polym Sci, 2017, 134, 1–8.
[51] Patel, D. K., Sakhaei, A. H., Layani, M., Zhang, B., Ge, Q., Magdassi, S. Highly stretchable
and UV curable elastomers for digital light processing based 3D printing, Adv Mater, 2017,
29, 1–7.
312 Ali Bagheri, Jianyong Jin

[52] Zhang, B., Kowsari, K., Serjouei, A., Dunn, M. L., Ge, Q. Reprocessable thermosets for
sustainable three-dimensional printing, Nat Commun, 2018, 9, 1831.
[53] Mu, Q., Wang, L., Dunn, C. K., Kuang, X., Duan, F., Zhang, Z., et al. Digital light processing 3D
printing of conductive complex structures, Addit Manuf, Elsevier B.V, 2017, 18, 74–83.
[54] Cullen, A. T., Price, A. D. Digital light processing for the fabrication of 3D intrinsically
conductive polymer structures, Synth Met, Elsevier, 2018, 235, 34–41.
[55] Tumbleston, J. R., Shirvanyants, D., Ermoshkin, N., Janusziewicz, R., Johnson, A. R., Kelly, D.,
et al. Continuous liquid interface production of 3D objects, Science, 2015, 347, 1349–1352.
[56] Janusziewicz, R., Tumbleston, J. R., Quintanilla, A. L., Mecham, S. J., DeSimone,
J. M. Layerless fabrication with continuous liquid interface production, Proc Natl Acad Sci,
2016, 113, 11703–11708.
[57] Fouassier, J. P., Allonas, X., Lalevée, J., Dietlin, C. Photoinitiators for Free Radical
Polymerization Reactions, Photochemistry and Photophysics of Polymeric Materials, Allen,
N. S. eds, John Wiley & Sons, Inc., Hoboken, New Jersey, 2010, 351–419.
[58] Palaganas, N. B., Mangadlao, J. D., De Leon, A. C. C., Palaganas, J. O., Pangilinan, K. D., Lee,
Y. J., et al. 3D printing of photocurable cellulose nanocrystal composite for fabrication of
complex architectures via stereolithography, ACS Appl Mater Interfaces, 2017, 9,
34314–34324.
[59] Warner, J., Soman, P., Zhu, W., Tom, M., Chen, S. Design and 3D printing of hydrogel
scaffolds with fractal geometries, ACS Biomater Sci Eng, 2016, 2, 1763–1770.
[60] Liska, R., Schuster, M., Inführ, R., Turecek, C., Fritscher, C., Seidl, B., et al. Photopolymers for
rapid prototyping, J Coatings Technol Res, 2007, 4, 505–510.
[61] Yue, J., Zhao, P., Gerasimov, J. Y., Van De Lagemaat, M., Grotenhuis, A., Rustema-Abbing, M.,
et al. 3D-printable antimicrobial composite resins, Adv Funct Mater, 2015, 25, 6756–6767.
[62] Al Mousawi, A., Garra, P., Sallenave, X., Dumur, F., Toufaily, J., Hamieh, T., et al. π-
conjugated dithienophosphole derivatives as high performance photoinitiators for 3D
printing resins, Macromolecules, 2018, 51, 1811–1821.
[63] Al Mousawi, A., Kermagoret, A., Versace, D. L., Toufaily, J., Hamieh, T., Graff, B., et al. Copper
photoredox catalysts for polymerization upon near UV or visible light: Structure/reactivity/
efficiency relationships and use in LED projector 3D printing resins, Polym Chem, 2017, 8,
568–580.
[64] Al Mousawi, A., Dumur, F., Garra, P., Toufaily, J., Hamieh, T., Graff, B., et al. Carbazole
scaffold based photoinitiator/photoredox catalysts: Toward new high performance
photoinitiating systems and application in LED projector 3D printing resins, Macromolecules,
2017, 50, 2747–2758.
[65] Al Mousawi, A., Garra, P., Schmitt, M., Toufaily, J., Hamieh, T., Graff, B., et al. 3-
Hydroxyflavone and N-Phenylglycine in high performance photoinitiating systems for 3D
printing and photocomposites synthesis, Macromolecules, 2018, 51, 4633–4641.
[66] Lovestead, T. M., O’Brien, A. K., Bowman, C. N. Models of multivinyl free radical
photopolymerization kinetics, J Photochem Photobiol A Chem, 2003, 159, 135–143.
[67] Ligon-Auer, S. C., Schwentenwein, M., Gorsche, C., Stampfl, J., Liska, R. Toughening of
photo-curable polymer networks: A review, Polym Chem, 2016, 7, 257–286.
[68] Moad, G., Rizzardo, E., Thang, S. H. Radical addition-fragmentation chemistry in polymer
synthesis, Polymer, 2008, 49, 1079–1131.
[69] Gorsche, C., Seidler, K., Knaack, P., Dorfinger, P., Koch, T., Stampfl, J., et al. Rapid formation
of regulated methacrylate networks yielding tough materials for lithography-based 3D
printing, Polym Chem, 2016, 7, 2009–2014.
 Chapter 9 3D printing mediated by photoRAFT polymerization process 313

[70] Seidler, K., Griesser, M., Kury, M., Harikrishna, R., Dorfinger, P., Koch, T., et al. Vinyl
sulfonate esters: Efficient chain transfer agents for the 3D printing of tough photopolymers
without retardation, Angew Chemie – Int Ed, 2018, 57, 9165–9169.
[71] Xu, J., Jung, K., Atme, A., Shanmugam, S., Boyer, C. A robust and versatile photoinduced
living polymerization of conjugated and unconjugated monomers and its oxygen tolerance,
J Am Chem Soc, 2014, 136, 5508–5519.
[72] Yagci, Y., Jockusch, S., Turro, N. J. Photoinitiated polymerization: Advances, challenges, and
opportunities, Macromolecules, 2010, 43, 6245–6260.
[73] Matthew, J. K., Daniel, J. B., Craig, J. H. The power of thiol‐ene chemistry, J Polym Sci Part A
Polym Chem, 2010, 48, 743–750.
[74] Senyurt, A. F., Wei, H., Phillips, B., Cole, M., Nazarenko, S., Hoyle, C. E., et al. Physical and
mechanical properties of photopolymerized thiol-ene/acrylates, Macromolecules, 2006, 39,
6315–6317.
[75] Sycks, D. G., Wu, T., Park, H. S., Gall, K. Tough, stable spiroacetal thiol-ene resin for 3D
printing, J Appl Polym Sci, 2018, 135, 1–12.
[76] Oesterreicher, A., Wiener, J., Roth, M., Moser, A., Gmeiner, R., Edler, M., et al. Tough and
degradable photopolymers derived from alkyne monomers for 3D printing of biomedical
materials, Polym Chem, Royal Society of Chemistry, 2016, 7, 5169–5180.
[77] McNair, O. D., Janisse, A. P., Krzeminski, D. E., Brent, D. E., Gould, T. E., Rawlins, J. W., et al.
Impact properties of thiol-ene networks, ACS Appl Mater Interfaces, 2013, 5, 11004–11013.
[78] Qin, X. H., Gruber, P., Markovic, M., Plochberger, B., Klotzsch, E., Stampfl, J., et al. Enzymatic
synthesis of hyaluronic acid vinyl esters for two-photon microfabrication of biocompatible
and biodegradable hydrogel constructs, Polym Chem, 2014, 5, 6523–6533.
[79] Bertlein, S., Brown, G., Lim, K. S., Jungst, T., Boeck, T., Blunk, T., et al. Thiol–Ene clickable
gelatin: A platform bioink for multiple 3D biofabrication technologies, Adv Mater, 2017, 29, 1–6.
[80] Fairbanks, B. D., Sims, E. A., Anseth, K. S., Bowman, C. N. Reaction rates and mechanisms for
radical, photoinitiated addition of thiols to alkynes, and implications for thiol-yne
photopolymerizations and click reactions, Macromolecules, 2010, 43, 4113–4119.
[81] Chan, J. W., Shin, J., Hoyle, C. E., Bowman, C. N., Lowe, A. B. Synthesis, thiol-yne “click”
photopolymerization, and physical properties of networks derived from novel multifunctional
alkynes, Macromolecules, 2010, 43, 4937–4942.
[82] Al Mousawi, A., Lara, D. M., Noirbent, G., Dumur, F., Toufaily, J., Hamieh, T., et al. Carbazole
derivatives with thermally activated delayed fluorescence property as photoinitiators/
photoredox catalysts for LED 3D printing technology, Macromolecules, 2017, 50, 4913–4926.
[83] Lalevée, J., Tehfe, M. A., Dumur, F., Gigmes, D., Graff, B., Morlet-Savary, F., et al. Light-
harvesting organic photoinitiators of polymerization, Macromol Rapid Commun, 2013, 34,
239–245.
[84] Fouassier, J. P., Allonas, X., Burget, D. Photopolymerization reactions under visible lights:
Principle, mechanisms and examples of applications, Prog Org Coatings, 2003, 47, 16–36.
[85] Fors, B. P., Hawker, C. J. Control of a living radical polymerization of methacrylates by light,
Angew Chemie – Int Ed, 2012, 51, 8850–8853.
[86] Xu, J., Shanmugam, S., Duong, H. T., Boyer, C. Organo-photocatalysts for photoinduced
electron transfer-reversible addition-fragmentation chain transfer (PET-RAFT) polymerization,
Polym Chem, Royal Society of Chemistry, 2015, 6, 5615–5624.
[87] Bagheri, A., Arandiyan, H., Adnan, N. N. M., Boyer, C., Lim, M. Controlled direct growth of
polymer shell on upconversion nanoparticle surface via visible light regulated
polymerization, Macromolecules, 2017, 50, 7137–7147.
[88] Cuthbert, J., Balazs, A. C., Kowalewski, T., Matyjaszewski, K. STEM Gels by controlled radical
polymerization, Trends Chem, Elsevier Inc, 2020, 2, 341–353.
314 Ali Bagheri, Jianyong Jin

[89] Chen, M., Gu, Y., Singh, A., Zhong, M., Jordan, A. M., Biswas, S., et al. Living additive
manufacturing: Transformation of parent gels into diversely functionalized daughter gels
made possible by visible light photoredox catalysis, ACS Cent Sci, 2017, 3, 124–134.
[90] Hill, M. R., Carmean, R. N., Sumerlin, B. S. Expanding the scope of RAFT polymerization:
Recent advances and new horizons, Macromolecules, 2015, 48, 5459–5469.
[91] Moad, G., Rizzardo, E., Thang, S. H. Living radical polymerization by the RAFT process, Aust
J Chem, 2002, 58, 379–410.
[92] Quinn, J. F., Barner, L., Barner-Kowollik, C., Rizzardo, E., Davis, T. P. Reversible addition –
Fragmentation chain transfer polymerization initiated with ultraviolet radiation,
Macromolecules, 2002, 35, 7620–7627.
[93] Otsu, T. Iniferter concept and living radical polymerization, J Polym Sci Part A Polym Chem,
2000, 38, 2121–2136.
[94] Nothling, M. D., Fu, Q., Reyhani, A., Allison-Logan, S., Jung, K., Zhu, J., et al. Progress and
perspectives beyond traditional RAFT polymerization, Adv Sci, 2020, 2001656, 1–12.
[95] Gruendling, T., Kaupp, M., Blinco, J. P., Barner-Kowollik, C. Photoinduced conjugation of
dithioester- and trithiocarbonate-functional raft polymers with alkenes, Macromolecules,
2011, 44, 166–174.
[96] Chen, M., Johnson, J. A. Improving photo-controlled living radical polymerization from
trithiocarbonates through the use of continuous-flow techniques, Chem Commun, 2015, 51,
6742–6745.
[97] Lu, L., Yang, N., Cai, Y. Well-controlled reversible addition-fragmentation chain transfer
radical polymerisation under ultraviolet radiation at ambient temperature, Chem Commun,
2005, 42, 5287–5288.
[98] Bagheri, A., Sadrearhami, Z., Adnan, N. N. M., Boyer, C., Lim, M. Surface functionalization of
upconversion nanoparticles using visible light-mediated polymerization, Polymer, Elsevier
Ltd, 2018, 151, 6–14.
[99] Amamoto, Y., Otsuka, H., Takahara, A., Matyjaszewski, K. Self-healing of covalently cross-
linked polymers by reshuffling thiuram disulfide moieties in air under visible light, Adv
Mater, 2012, 24, 3975–3980.
[100] Pan, X., Jiang, G., Zhu, X., Zhu, J., Fan, C., Zhang, Z., et al. Photocatalyst-free and blue light-
induced RAFT polymerization of vinyl acetate at ambient temperature, Macromol Rapid
Commun, 2015, 36, 2181–2185.
[101] McKenzie, T. G., Fu, Q., Wong, E. H. H., Dunstan, D. E., Qiao, G. G. Visible light mediated
controlled radical polymerization in the absence of exogenous radical sources or catalysts,
Macromolecules, 2015, 48, 3864–3872.
[102] Xu, J., Shanmugam, S., Boyer, C. Organic electron donor-acceptor photoredox catalysts:
Enhanced catalytic efficiency toward controlled radical polymerization, ACS Macro Lett, 2015,
4, 926–932.
[103] Niu, J., Lunn, D. J., Pusuluri, A., Yoo, J. I., O’Malley, M. A., Mitragotri, S., et al. Engineering
live cell surfaces with functional polymers via cytocompatible controlled radical
polymerization, Nat Chem, Nature Publishing Group, 2017, 9, 537–545.
[104] Tucker, B. S., Coughlin, M. L., Figg, C. A., Sumerlin, B. S. Grafting-from proteins using metal-
free PET-RAFT polymerizations under mild visible-light irradiation, ACS Macro Lett, 2017, 6,
452–457.
[105] Yang, Y., Liu, X., Ye, G., Zhu, S., Wang, Z., Huo, X., et al. Metal-free photoinduced electron
transfer-atom transfer radical polymerization integrated with bioinspired polydopamine
chemistry as a green strategy for surface engineering of magnetic nanoparticles, ACS Appl
Mater Interfaces, 2017, 9, 13637–13646.
 Chapter 9 3D printing mediated by photoRAFT polymerization process 315

[106] Ohtsuki, A., Goto, A., Kaji, H. Visible-light-induced reversible complexation mediated living
radical polymerization of methacrylates with organic catalysts, Macromolecules, 2013, 46,
96–102.
[107] Figg, C. A., Hickman, J. D., Scheutz, G. M., Shanmugam, S., Carmean, R. N., Tucker, B. S.,
et al. Color-coding visible light polymerizations to elucidate the activation of
trithiocarbonates using eosin y, Macromolecules, 2018, 51, 1370–1376.
[108] Bagheri, A., Yeow, J., Arandiyan, H., Xu, J., Boyer, C., Lim, M. Polymerization of a
photocleavable monomer using visible light, Macromol Rapid Commun, 2016, 37, 905–910.
[109] Xu, J., Jung, K., Boyer, C. Oxygen tolerance study of photoinduced electron transfer-reversible
addition-fragmentation chain transfer (PET-RAFT) polymerization mediated by Ru(bpy)3Cl2,
Macromolecules, 2014, 47, 4217–4229.
[110] Shanmugam, S., Xu, J., Boyer, C. Exploiting Metalloporphyrins for Selective Living Radical
Polymerization Tunable over Visible Wavelengths, J Am Chem Soc, 2015, 137, 9174–9185.
[111] Corrigan, N., Rosli, D., Jones, J. W. J., Xu, J., Boyer, C. Oxygen tolerance in living radical
polymerization: Investigation of mechanism and implementation in continuous flow
polymerization, Macromolecules, 2016, 49, 6779–6789.
[112] Li, S., Han, G., Zhang, W. Photoregulated reversible addition-fragmentation chain transfer
(RAFT) polymerization, Polym Chem, Royal Society of Chemistry, 2020, 11, 1830–1844.
[113] Moad, G. RAFT (Reversible addition-fragmentation chain transfer) crosslinking (co)
polymerization of multi-olefinic monomers to form polymer networks, Polym Int, 2015, 64,
15–24.
[114] Scott, T. F., Schneider, A. D., Cook, W. D., Bowman, C. N. Photoinduced plasticity in cross-
linked polymers, Science, 2005, 308, 1615–1617.
[115] Nicolaÿ, R., Kamada, J., Van Wassen, A., Matyjaszewski, K. Responsive gels based on a
dynamic covalent trithiocarbonate cross-linker, Macromolecules, 2010, 43, 4355–4361.
[116] Amamoto, Y., Otsuka, H., Takahara, A., Matyjaszewski, K. Changes in network structure of
chemical gels controlled by solvent quality through photoinduced radical reshuffling
reactions of trithiocarbonate units, ACS Macro Lett, 2012, 1, 478–481.
[117] Zhou, H., Johnson, J. A. Photo-controlled growth of telechelic polymers and end-linked
polymer gels, Angew Chemie – Int Ed, 2013, 52, 2235–2238.
[118] Bagheri, A., Arandiyan, H., Boyer, C., Lim, M. Lanthanide-doped upconversion nanoparticles:
Emerging intelligent light-activated drug delivery systems, Adv Sci, 2016, 3, 1500437.
[119] Dadashi-Silab, S., Doran, S., Yagci, Y. Photoinduced electron transfer reactions for
macromolecular syntheses, Chem Rev, 2016, 116, 10212–10275.
[120] Ciftci, M., Batat, P., Demirel, A. L., Xu, G., Buchmeiser, M., Yagci, Y. Visible light-induced
grafting from polyolefins, Macromolecules, 2013, 46, 6395–6401.
[121] Tasdelen, M. A., Ciftci, M., Yagci, Y. Visible light-induced atom transfer radical
polymerization, Macromol Chem Phys, 2012, 213, 1391–1396.
[122] Al Mousawi, A., Dumur, F., Garra, P., Toufaily, J., Hamieh, T., Goubard, F., et al. Azahelicenes
as visible light photoinitiators for cationic and radical polymerization: Preparation of
photoluminescent polymers and use in high performance LED projector 3D printing resins,
J Polym Sci Part A Polym Chem, 2017, 55, 1189–1199.
[123] Lampley, M. W., Harth, E. Photocontrolled growth of cross-linked nanonetworks, ACS Macro
Lett, American Chemical Society, 2018, 7, 745–750.
[124] Wendel, B., Rietzel, D., Kühnlein, F., Feulner, R., Hülder, G., Schmachtenberg, E. Additive
processing of polymers, Macromol Mater Eng, 2008, 293, 799–809.
[125] Jungst, T., Smolan, W., Schacht, K., Scheibel, T., Groll, J. Strategies and molecular design
criteria for 3D printable hydrogels, Chem Rev, 2016, 116, 1496–1539.
316 Ali Bagheri, Jianyong Jin

[126] Mondschein, R. J., Kanitkar, A., Williams, C. B., Verbridge, S. S., Long, T. E. Polymer
structure-property requirements for stereolithographic 3D printing of soft tissue engineering
scaffolds, Biomaterials, Elsevier Ltd, 2017, 140, 170–188.
[127] Bagheri, A., Boyer, C., Lim, M. Synthesis of light-responsive pyrene-based polymer
nanoparticles via polymerization-induced self-assembly, Macromol Rapid Commun, 2019,
40, 1800510.
[128] McKenzie, T. G., Fu, Q., Uchiyama, M., Satoh, K., Xu, J., Boyer, C., et al. Beyond traditional
RAFT: Alternative activation of thiocarbonylthio compounds for controlled polymerization,
Adv Sci, 2016, 3, 1–9.
[129] Lee, I. H., Discekici, E. H., Anastasaki, A., De Alaniz, J. R., Hawker, C. J. Controlled radical
polymerization of vinyl ketones using visible light, Polym Chem, Royal Society of Chemistry,
2017, 8, 3351–3356.
[130] Matyjaszewski, K., Coca, S., Gaynor, S. G., Wei, M., Woodworth, B. E. Controlled radical
polymerization in the presence of oxygen, Macromolecules, 1998, 31, 5967–5969.
[131] Xu, J., Shanmugam, S., Fu, C., Aguey-Zinsou, K. F., Boyer, C. Selective photoactivation: From
a single unit monomer insertion reaction to controlled polymer architectures, J Am Chem Soc,
2016, 138, 3094–3106.
[132] Nomeir, B., Fabre, O., Ferji, K. Effect of tertiary amines on the photoinduced electron transfer-
reversible addition–fragmentation chain transfer (PET-RAFT) polymerization,
Macromolecules, 2019, 52, 6898–6903.
[133] Fu, Q., Xie, K., McKenzie, T. G., Qiao, G. G. Trithiocarbonates as intrinsic photoredox
catalysts and RAFT agents for oxygen tolerant controlled radical polymerization, Polym
Chem, Royal Society of Chemistry, 2017, 8, 1519–1526.
H. Lai, P. Xiao
Chapter 10
Main challenges in 3D printing: Printing
speed and biomedical applications
10.1 Introduction
3D-printing, also known as additive manufacturing, is defined as a process to create
3D objects by the sequential layer-by-layer addition of materials with the assistance
of a computer-aided design (CAD). Compared to conventional formative or subtrac-
tive manufacturing that is based on molds or machining, 3D printing is more en-
ergy- and material-efficient, capable of creating objects with complex geometries
and is compatible with bio systems [1, 2]. From the time of its development in the early
1980s for the purpose of model making and rapid prototyping, this technology has
been advancing rapidly to find wide applications in engineering, chemistry, biology,
medicine and materials science [2–5]. Several 3D-printing approaches have been
developed, which are defined by the patterning and solidification process [6].
These include methods based on jetting, powder bed fusion, extrusion and photo-
polymerization, involving applicable materials ranging from thermoplastics and
polymeric resins to inorganic powders [7]. Comprehensive introductions about the
categories of 3D printing technologies and their respective working methodology
have been given in previous publications [2, 6, 8]. The current research efforts in
3D printing are mainly devoted to the innovations in 3D printing methods and the
adaptation of the developed techniques in various sectors including customized
manufacturing, architecture design and medical fields [9–12].
One major issue for 3D printing to be used in manufacturing on a large scale is
related to the printing speed – the rate to convert the digital information stored as
units of bits in CAD model into physical objects [13]. However, most of the estab-
lished 3D printing methods that rely on layer-by-layer deposition are too sluggish to
meet the demands for printing of large objects and high-throughput manufacturing.
It can take hours to build an object with height of several centimeters by the current
stereolithography (SLA) systems [14, 15]. It has been indicated that an order of mag-
nitude increase in printing speed without a compromise on part accuracy (resolu-
tion or voxel size) is the premise for these methods in mass production [15].
However, this seems to be a difficult goal to achieve as an inherent trade-off exists
between the resolution, build volume and speed with all 3D printing methods [6].
For instance, a reduction of the voxel size by a factor of ten requires a 1000-fold

H. Lai, P. Xiao, Research School of Chemistry, The Australian National University, Canberra,
Australia

https://doi.org/10.1515/9783110570588-010
318 H. Lai, P. Xiao

increase in the printing speed [13]. To tackle this challenge, innovations in 3D print-
ing have emerged with new materials and processes towards faster solidification
and deposition. They are discussed in this chapter.
On the other hand, 3D printing was born to limitlessly build structures with geo-
metric complexities. This feature has been frequently exploited in the pharmaceutical
field for on-demand dosage forms and personalized drug delivery. In addition,
human body represents one of the most complex systems, organized with tissues and
organs that comprise multiple cell types and the related supporting extracellular ma-
trix (ECM). Even since the first U.S. patent was awarded in 2006 for 3D bioprinting
[2], 3D printing of tissues and organs has become a focus of interest in 3D printing
area and the field of regenerative medicine. These include the bioprinting of skin,
vascular grafts, heart tissue and cartilaginous structures, representing the state-of-
the-art applications of 3D printing in tissue engineering and regenerative medicine.
Herein, we focus on the recent innovations and challenges in which the 3D print-
ing technology has advanced with a dramatic reduction in build-time. We also high-
light the applications of 3D printing in biomedical areas (including pharmaceutics
and bioprinting of tissues and organs) with detailed examples. In addition, we share
our perspective on the future directions about this rapidly evolving area of research.

10.2 Innovation and challenges to advance

the printing speed
The traditional 3D printing was limited by printing speed with the bottleneck being
the time-consuming step-wise point-by-point or layer-by-layer deposition processes
[1, 15]. To unleash the practical potential of 3D printing, innovations utilizing new
materials and printing methods to allow for rapid material deposition with high pre-
cision have accelerated the printing process significantly over the past few years [6].

10.2.1 New materials for fast printing

It has been indicated that an instantaneous replenishment of the liquid resin after
the curing of one layer in photocuring could lead to great advance in printing speed
[16]. This generally requires the employment of monomers with low viscosity. The
digital light projection (DLP) printing of thermoplastic polymers from a monofunc-
tional monomer, 4-acryloylmorpholine (ACMO in Figure 10.1(a)), was demonstrated
[16]. Specifically, this low-viscosity monomer showed fast polymerization kinetic to
generate high molecular weight polymers with Tg above the print temperature (Fig-
ure 10.1(b)), which was adapted to a top-down DLP printing process. Natural air
was exploited to create an inhibition layer on the top of the resin to favor the fast
 Chapter 10 Main challenges in 3D printing 319

Figure 10.1: Rapid open‐air DLP Printing of thermoplastic ACMO resin. (a) The printing setup and
formulations. (b) The curing kinetics of the ACMO resin and a commercial thermoset acrylate resin.
(c) Printed parts. (d) Printed pillars with different radii (left to right, 150, 200, 400 and 800 µm)
demonstrating the resolution. All the printed 150 µm pillars and half of the 200 µm pillars
collapsed. (e) Micro Kelvin lattice with fine struts. Reprinted with permission from [16].
Copyright 2019 John Wiley and Sons.
320 H. Lai, P. Xiao

spreading of fresh resin onto the printed part, allowing the successful printing of
various 3D objects with complex features (overhang, hollow and lattice showed in
Figure 10.1(c)). This requires an upper limit of 3s on the irradiation time to maintain
the inhibition layer. A print speed of 730 mm h−1 could be achieved with good struc-
tural fidelity, with resolution in the range of 200 and 400 µm (Figure 10.1(d, e)). With
its unique thermoplastic and water-soluble feature, the printed objects were sought
after for uses as sacrificial molds. The printed resin could be removed by melting or
dissolution to fabricate 3D functional devices such as microfluidic devices [16].
Besides, 3D objects can also be developed from 2D structures. These are rapidly
printed with digital projectors capable of dynamic spatial control of the light expo-
sure time [1]. The different light exposure results in a variable crosslinking density
within the created 2D network, leading to stresses that can be released upon trigger-
ing and the development of the network into 3D designed objects. This concept is
also widely used in 4D printing. The single brief digital light exposure overcomes
the layer-by-layer deposition of material and enables quick printing of 3D objects
with stimuli response [1].
More interestingly, the development of highly efficient photoinitiators capable
of inducing fast photopolymerization reactions is a promising and emerging strat-
egy to enhance the 3D printing speed especially under the longer wavelength light
irradiation. The relevant details are presented in Chapter 1.

10.2.2 New approaches for fast printing

Apparently, there is a leap in the printing speed by the replacement of the rastering
laser in SLA with DLP. Printers that use a bladder to replenish the resin after each
printing cycle and subsequently reposition consume a large percentage of time col-
lectively to complete the printing of an object. This process is found in DLP, selec-
tive laser sintering (SLS) and binder jetting (BJ) technology. The printing in additive
manufacturing can be greatly accelerated and a remarkable reduction of printing
time can be achieved if the inherent flaws of layer-wise addition process can be mit-
igated or overcome [17].
The continuous liquid interface production (CLIP) method takes advantage of
the oxygen-inhibition effect in photopolymerization [15]. In this approach, a “dead
zone” is created between the cured frontier and oxygen-permeable window, ensur-
ing a continuous interface of the liquid resin below the advancing part (Figure 10.2
(a)), thereby eliminating the resin replenishment process. The continuous elevation
of the build-support and the projection of the UV images through the window en-
able a continuous printing process. The printed objects are drawn out from the
resin bath at rates of hundreds of millimeters per hour, in contrast to a few milli-
meters per hour in the layer-wise approaches. Moreover, CLIP also shows promise
in the fabrication of large overhangs that benefit from the isotropic mechanical
Figure 10.2: Schematic illustration of continuous 3D printing using (a) oxygen inhibition technique (b) concurrent
photopolymerization and photoinhibition.
Chapter 10 Main challenges in 3D printing
321
322 H. Lai, P. Xiao

properties, which are independent of the slice layer thickness. It was pointed out
that the print speed for CLIP could be further increased by optimizing the resin cure
rates and viscosity [15].
Following the CLIP work, a photoinhibition process is utilized instead of oxygen to
create the “dead zone”, which is called the “inhibition volume” (Figure 10.2(b)) [14].
The bis[2-(ochlorophenyl)-4,5-diphenylimidazole] (o-Cl-HABI; Figure 10.2(b)) is
adopted in the system as a photoinhibitor to trap the propagating species generated
from camphorquinone (CQ)/ethyl-4-dimethylamino benzoate (EDAB) two-component
photoinitiating system. Photoinitiation and photoinhibition are achieved by the blue
and UV light, respectively, according to their absorbance spectra. The oxygen-
permeable window in CLIP is thus replaced by a glass-transparent window. The
thickness of the “inhibition volume” above the glass window is manipulated by
changing the relative intensities of the two illuminating light sources and the con-
centrations of o-Cl-HABI. The thickness can, therefore, be tuned to hundreds of
micrometers, which is much higher than the tens of micrometers in the CLIP ap-
proach. This greatly facilitates the reflow of resin underneath the printing frontier,
allowing the printing of viscous resin and large cross-sectional areas objects. The
printing speed is dependent on the absorption heights and the intensity of the
two irradiations. Objects can be printed with a speed of up to 2 m/hour by optimiz-
ing these parameters.
By flowing a layer of fluorinated oil beneath the photocuring resin, the continu-
ous high-area rapid printing (HARP) process was developed [18]. In this approach,
a slip boundary is created beneath the emerging part as a result of a shear stress
caused by the oil motion (Figure 10.3). It was found that a mobile interface and

Figure 10.3: Schematic illustration of high-area rapid printing.

 Chapter 10 Main challenges in 3D printing 323

active cooling are essential for heat dissipation, otherwise the accumulating heat
would exceed the flashpoint of the resin, leading to part-cracking or result in re-
duced effectiveness at the slip boundary. By cooling the flowing oil, large parts can
be printed with volumetric throughputs of 100 liters/hour. Moreover, without de-
pending on oxygen inhibition to create a dead zone, HARP printing was also compat-
ible with oxygen sensitive resin. Additionally, the HARP-printed material exhibited
isotropic mechanical properties with high structure fidelity. These features together
make the approach promising for rapid printing of large-objects.
The transition from the step-wise process to a continuous process significantly
accelerates printing, but the CLIP and HARP printing methods still remain in the cat-
egory of layer-by-layer printing. Inspired by the image reconstruction of computed
tomography (CT), the computed axial lithography (CAL) 3D printing technique,
which photopolymerizes all points within the 3D object at once, was developed [19,
20]. It is based on the time-sequenced projection of light pattern to a rotating viscous
resin [21]. Photocuring occurs at the superposed position from multiple angles, which
accumulates sufficient exposures to overcome oxygen inhibition. Objects with lateral
sizes up to ~ 55 mm can be printed rapidly in the range of 30 to 120 s and all parts
materialize as a whole simultaneously in a support-free manner. The layerless print-
ing allows objects to be printed with exceptionally smooth surface finishes or without
support. Printing on preexisted parts can also be achieved, opening avenues for
multi-materials fabrication, soft materials creation and lenses with smooth curved sur-
faces [19]. It was proved that a feedback camera could be integrated to CLA printing,
perpendicular to the direction of illumination, to record the photocuring information,
which could be used to optimize subsequent prints and improve the geometric fidelity
of the object solidification [21].
Even though extensive efforts have been devoted to enhancing 3D printing
speed, it still remains a great challenge especially in industrial applications.

10.3 Advancement in the biomedical applications

of 3D printing
10.3.1 3D-printed drug delivery devices

3D printing for drug delivery is rapidly expanding with the aim of reducing the side
effects and ensuring personalized medicine such as on-demand dosage forms that
meet the specific pharmacogenomic, anatomical and physiological demands of pa-
tients [4, 22]. Different drug releasing profiles are needed corresponding to the dif-
ferent clinical circumstances such as constant, pulsatile, increasing and decreasing
release. A general method for customizing the drug carriers for various release
profiles has been challenging with the conventional materials-filling approach.
324 H. Lai, P. Xiao

3D printing is employed to fabricate drug tablets with any kind of desired drug
release profiles [23]. Specifically, a polymeric template with an embossed feature
of the desired shape and an impermeable poly(L-lactic acid) (PLA) container is at
first 3D printed with a commercially available extrusion 3D printer. A mold is then
cured complementary to the template. A surface-eroding polymer containing the
drug is photocured in the mold and is inserted into the PLA container, which is
followed by infilling of a polymer solution without the drug into the void spaces
and photocured. The drug is allowed to release from the top of the tablet that is
capped with an additional layer of surface-eroding polymer. The release is 1-
dimentional and follows the shape of the drug-containing polymer. The versatility
of this method for 3D printed tablets was proved with constant, pulsed, decreas-
ing and increasing profiles and arbitrary profiles (Figure 10.4). The entire duration
of the release can be tuned by adjusting the crosslinking density within the sur-
face-eroding polymer. Interestingly, multiple drugs with different release profiles
can be encapsulated in one tablet, demonstrating the possibility of simultaneous
administration of multiple drugs [23].
A 3D printed personalized wearable mouthguard with sustained drug release
capability was demonstrated [24]. In this approach, the dentition impressions ob-
tained from individualized intraoral scans were used to build CAD models tailored
to patient-specific anatomic features. Clobetasol propionate (CBS), which is an ef-
fective oral anti-inflammation drug with high thermal stability, was chosen as the
model drug and blended with PLA and poly(vinyl alcohol) (PVA) before 3D printing
into the mouthguard via fused deposition modeling (FDM) printing. The release
rate of CBS from the mouthguard can be tuned by varying the feed ration of PLA
and PVA, with higher PVA content facilitating a faster release. The drug loading re-
gions were also manipulated to allow spatial placement of drugs. CBS was replaced
with the food-grade flavor vanillic acid (VA) and the mouthguards were printed
with pharmaceutical-grade filaments for human release study. A sustained release
of VA from the mouthguard over the duration of wearing was found, which can
boost treatment efficacy and reduce unwanted side effects.
 Chapter 10 Main challenges in 3D printing

Figure 10.4: The expected and the experimentally determined release profiles of dye from the tablets. Reprinted with permission from [23].
Copyright 2015 John Wiley and Sons.
325
326 H. Lai, P. Xiao

10.3.2 Innovations of 3D printing for engineered tissues

and organs
Due to its potential to fabricate personalized complex constructs, 3D printing of en-
gineered tissues and organs has been treated as one of the promising approaches to
address the rising demand for transplantation in opposition to the limited availability
of donors [5, 25–27]. Compared to nonbiological 3D-printed constructs, 3D bioprinting
faces more complexities: 1) They need to be made of printable and biologically func-
tional materials (bioink) that are compatible with cells and can be degraded into
nonharmful byproducts while being capable of maintaining the structural and me-
chanical properties corresponding to the native organs; 2) There is a need to establish
methods to expand and harvest sufficient cells for printing; 3) The printing calls for
deposition of multiple cell types within patterns that mimic the complex micro-
architecture; 4) The printing should create vasculature networks mimicking arteries,
veins and capillaries within the printed constructs to allow the perfusion of nutrition
and oxygen. With the development of engineering in 3D printers, biomaterials sci-
ence and cell biology, the printing of simple tissues or simplified models of organs
has succeeded as exemplified below [5, 25, 28].
As mentioned, the properties of bioinks are of great importance to affect the
mechanical performance and the viability of cells in the printed constructs. Thus,
effective bioinks for printing of 3D tissues are highly sought after. It was reported
that methacrylated silk fibroin (Sil-MA) could be used to print highly complex
organ structures via DLP 3D bioprinting [29]. Sil was chemically modified in the
amino groups by glycidyl methacrylate (GMA) and the modification degree was
tuned by varying the amount of GMA. The mechanical properties of the hydrogels
prepared via photopolymerization were thus manipulated by the modification de-
gree, with a higher methacrylation resulting in an increased tensile strength. The
successful DLP printing of methacrylated silk fibroin with a 30% methacrylation de-
gree was proved with various objects including the Eiffel Tower apart from the
brain and ear that could return to their original shapes without deformation after
compression. Tubular organs and tissues with complex structures were also suc-
cessfully printed with good mechanical integrity (Figure 10.5). The hydrogel was
found to be compatible with cells, regardless of the concentration and methacryla-
tion degree. Moreover, the hydrogel exhibited excellent degradability, with 50%
degradation after 4 weeks’ cultivation in 30% Sil-MA hydrogel [29].
The capability of an integrated tissue–organ printer (ITPO) was demonstrated to
fabricate human-scale constructs using cell-laden hydrogels and biodegradable poly-
mers [26]. Specifically, four-cartridge modules were employed as material dispensers.
Among the four modules, two of them delivered poly(ε-caprolactone) (PCL) polymer
and a sacrificial Pluronic F-127 hydrogel, respectively, to impart mechanical strength.
The other two modules delivered cell-laden hydrogels. Two patterns were designed by
varying the placement of PCL for different resultant mechanical strengths, depending
 Chapter 10 Main challenges in 3D printing 327

Figure 10.5: Printed products by DLP using Sil-MA showed complex structure reflecting their CAD
images, including veins, arteries, folds and holes. Adapted with permission from [29]. Copyright
2018 Springer Nature.

on the aimed tissues or organs. The Type I pattern was designed with PCL frames
woven throughout the constructs to engineer mandible and calvarial bone and ear
cartilage. In contrast, PCL only formed the exterior in Type II pattern with a softer
structure to mimic the skeletal muscle. The cell-laden hydrogels were organized to
create microchannels to allow maximal diffusion of nutrients and oxygen, which
maintained cell viability and proliferation in the constructs. The cells embedded in
the constructs can thereby differentiate and mature into vascularized functional tis-
sues. This was demonstrated by the observation of calcium deposition in the mandi-
ble bone and in the newly formed vascularized bone tissue throughout the calvarial
bone, both of which were printed with osteogenic stem cell-laden hydrogel. In ad-
dition, the ear cartilage exhibited much higher resilience after in vivo implanta-
tion. The implanted muscle constructs printed with Type II pattern also showed
328 H. Lai, P. Xiao

response to electrical stimulation. Based on these results, it is envisioned that

ITPO may produce tissues for human applications, benefitting from the transport
of nutrients and oxygen within the vascular constructs.
By considering the immune risk of biomaterials and heterogeneous tissues, au-
tologous materials were utilized to engineer personalized cardiac patches and heart
via 3D printing [30]. The strategy began from the extraction of a biopsy of omental
tissue from a patient (Figure 10.6). The extra-cellular matrix was processed into a
personalized bioink, while cells were separated and reprogrammed to form induced
pluripotent stem cells (iPSCs). The iPSCs were further developed into cardoimyo-
cytes (CMs) and endothelial cells (ECs) to construct the parenchymal cardiac tissue
and blood vessels. A patch model was obtained from the CT of a patient heart and
with assistance of a mathematical model. A thick patch (~2 mm) was 3D printed
with two print heads. One contained CMs in personalized hydrogel and the other
contained EMs mixed with gelatin. Gelatin was sacrificed after printing and a vascu-
larized cardia patch with physical robustness was obtained, which enabled perfusion
of liquid. The in vivo contractility potential was also verified. To print a heart with
significantly higher weight, a supporting medium composed of alginate micropar-
ticles in xanthan gum-supplemented growth medium was introduced. The printed
heart with major blood vessels was shown to possess basic anatomical architecture

Figure 10.6: Schematic process of 3D printing of personalized thick and perfusable cardiac patches
and hearts. Reprinted with permission from [30]. Copyright 2019 John Wiley and Sons.
 Chapter 10 Main challenges in 3D printing 329

and mechanical strength. Challenges remain in whole organ printing, including im-
aging of the finer vessels and reproducing them during printing.
Reproducing a more specific heart anatomical structure was realized by the 3D-
bioprint collagen using freeform reversible embedding of suspended hydrogels
(FRESH) [31]. The challenge to support soft materials during printing to maintain
high resolution and fidelity was overcome by a rapid pH change-driven-collagen
self-assembly within a buffered support material (from ~ 3.5 to 7.4). The support ma-
terial was composed of gelatin microparticle slurry and underwent reversible melt-
ing at 37 °C to release the printed scaffolds. The slurry, called FRESH v2.0, was
modified from the previous report with improved resolution in extruded collage
filament [32]. With this support, collagen can be directly printed to form the walls
of functional vasculature, promoting cell infiltration and microvascularization. A
model of the left ventricle of a human heart was printed using collagen and cell-
laden as dual bio-inks with an ellipsoidal shape and a sandwich structure, where
the inner and outer shells were made of collagen-encapsulated human embryonic
stem cell–derived cardiomyocytes (hESC-CMs). Directional propagating waves during
the spontaneous contractions of hESC-CMs could be captured. A tri-leaflet heart valve
with a diameter of 28 mm was built and its mechanical function to cyclically open
and close the valve leaflets was proved in a pulsatile flow test. A vascular network
from the left coronary arteries was reproduced with FRESH approach. Ultimately,
half of a neonatal scale human heart was printed with well-defined microstructures,
including trabeculae, atrial and ventricular chambers.
The stereolithographic apparatus for tissue engineering (SLATE) was used to
fabricate multivascular networks from 3D printed hydrogels composed of water and
poly(ethylene glycol) diacrylate in the presence of photoabsorbing additives [33,
34]. A water-soluble food additive, tartrazine, was added to the formulation as a
photo-blocker to minimize the light that penetrated the printing layer during poly-
merization, thereby increasing the z resolution and ensuring the creation of a hol-
low perfusable vasculature. With this approach, monolithic hydrogels with an
integrated static mixer or an integrated 3D bicuspid valve within the vasculature
were printed. Rapid mixing dependent on the fin numbers of mixer and rapid re-
sponse to pulsatile anterograde and retrograde flows by the valve, respectively,
were both demonstrated. Complex entangled networks capable of independently
flowing fluids were constructed based on 3D mathematical algorithms. One en-
tangled helical topology was printed with a serpentine channel and perfused with
oxygen gas. As a result, the inflowed deoxygenated RBCs changed color from dark
red to bright red, suggesting intervascular interstitial transport. Besides, a biomi-
metic alveolar model with a shared airway atrium and an ensheathing vasculature
were developed and printed into hydrogels. The airway was cyclically ventilated by
oxygen to oxygenate the RBC streams perfusing in the surrounding vasculature.
The architecture also supported the proliferation and differentiation of human stem
cells [33].
330 H. Lai, P. Xiao

The application of a microscale continuous projection printing (μCPP) method

was demonstrated to fabricate biomimetic hydrogel scaffolds that could accommo-
date neural progenitor cells (NPCs) for axon regeneration from spinal cord injury in
the central nervous system [35]. Polyethylene glycol–gelatin methacrylate was used
as the photo-bioink to engineer the rat spinal cord scaffold, which mimicked the ge-
ometries with an H-shaped solid area representing the ‘gray matter’ area and micro-
channels of 200 μm diameter to host NPCs and provide alignment with the host
axonal tracts, above and below the injury. Host and stem cell-derived axons were
found to linearly traverse the scaffold channels and form neural relays via
electrophysiological transmission after implantation of the NPCs-loaded scaf-
folds at the transection site. The method opens up an avenue for the fabrication
of personalized scaffolds that ‘fit’ the precise anatomy of an individual injury to
enhance the central nervous system regeneration.
Moreover, the state-of-the-art development of novel 3D printable photocurable
biomacromolecules, especially in the aspect of the design of relevant chemical
structures, is given in Chapter 5.

10.4 Conclusions and perspectives

The demands for innovations in 3D printing are accompanied by the wide applica-
tions of 3D printing in various areas, emphasizing a more rapid fabrication with
higher resolutions in larger volumes. Once a new printing technique is developed
with better performance in speed, resolution or size, it is rapidly adopted by the re-
search community to advance the respective areas. For instance, the CLIP has been
widely used in 3D printing of tissue scaffolds [35] and medical devices [36, 37], soon
after its release in 2015. The potential of CAL 3D printing to rapidly create entire
objects at once was exploited to fabricate, within seconds, entire cell-laden con-
structs with arbitrary size and architecture [19, 38] Despite the remarkable achieve-
ments, there are still several aspects of the printing technology that need to be
enhanced to completely meet the requirements of printing constructs with complex-
ities that are relevant to tissues and organs.
The current 3D printing approaches remain generally limited to single-material
fabrication. Progress that allows the local fabrication with customized 3D spatial in-
tegration of dissimilar materials (such as metals, ceramics and polymers) in a single
build sequence can unleash the end-use functionality of the fabricated structures.
Simultaneous printing of several materials can be achieved with several syringes in
direct ink writing [39]. The jetting of resin droplets composed of different materials
at the same location, followed by polymerization, enables the formation of hybrid
solid voxel in inkjet-based 3D printing [39]. The ability of CAL techniques to
 Chapter 10 Main challenges in 3D printing 331

photopolymerize resins around a preexisting structure is also highly promising to

integrate other materials for multimaterial fabrication [19].
The bioprinting of tissues and organs is also facing significant hurdles and
challenges before real applications. The fabrication must be accelerated to a level
that clinically-relevant-sized-tissues or organs can be manufactured with high cell
viability in the constructs [5]. Methods to produce large number of functional cells
from stem cells need to be developed for large organs printing. The integration of
multiple types of functional, progenitor and supporting cell types in printed tissues
remains elusive. Moreover, within tissues or organs of clinically relevant size, vas-
cularization is a critical factor for oxygen and nutrient diffusion to allow cell sur-
vival in clinically relevant-sized 3D printed tissues. A complete multiscale vascular
network, spanning arteries and veins down to the smallest capillaries, is still be-
yond the current fabrication approaches. Significant progresses in cell biology and
the combination of different bioprinting modalities and bioinks are required to
solve these problems to allow fabrication of clinically relevant-sized tissues or or-
gans that can be used for transplantation.

References
[1] Huang, L., Jiang, R., Wu, J., Song, J., Bai, H., Li, B., Zhao, Q., Xie, T. Ultrafast digital printing
toward 4D shape changing materials, Adv Mater, 2017, 29(7), 1605390.
[2] Ligon, S. C., Liska, R., Stampfl, J., Gurr, M., Mülhaupt, R. Polymers for 3D printing and
customized additive manufacturing, Chem Rev, 2017, 117(15), 10212–10290.
[3] Hartings, M. R., Ahmed, Z. Chemistry from 3D printed objects, Nat Rev Chem, 2019, 3(5),
305–314.
[4] Capel, A. J., Rimington, R. P., Lewis, M. P., Christie, S. D. R. 3D printing for chemical,
pharmaceutical and biological applications, Nat Rev Chem, 2018, 2(12), 422–436.
[5] Murphy, S. V., Atala, A. 3D bioprinting of tissues and organs, Nat Biotechnol, 2014, 32(8),
773–785.
[6] Truby, R. L., Lewis, J. A. Printing soft matter in three dimensions, Nature, 2016, 540(7633),
371–378.
[7] Ahn, D., Stevens, L. M., Zhou, K., Page, Z. A. Rapid high-resolution visible light 3D printing,
ACS Cent Sci, 2020, 6(9), 1555–1563.
[8] Ambrosi, A., Pumera, M. 3D-printing technologies for electrochemical applications, Chem Soc
Rev, 2016, 45(10), 2740–2755.
[9] Au, A. K., Huynh, W., Horowitz, L. F., Folch, A. 3D-Printed Microfluidics, Angew Chem Int Ed,
2016, 55(12), 3862–3881.
[10] Zhou, L.-Y., Fu, J., He, Y. A Review of 3D printing technologies for soft polymer materials, Adv
Funct Mater, 2020, 30(28), 2000187.
[11] Powell, S. K., Cruz, R. L. J., Ross, M. T., Woodruff, M. A. Past, present, and future of soft-
tissue prosthetics: Advanced polymers and advanced manufacturing, Adv Mater, 2020,
32(42), 2001122.
[12] Wallin, T. J., Pikul, J., Shepherd, R. F. 3D printing of soft robotic systems, Nat Rev Mater,
2018, 3(6), 84–100.
332 H. Lai, P. Xiao

[13] Hahn, V., Kiefer, P., Frenzel, T., Qu, J., Blasco, E., Barner-Kowollik, C., Wegener, M. Rapid
assembly of small materials building blocks (Voxels) into large functional 3D metamaterials,
Adv Funct Mater, 2020, 30(26), 1907795.
[14] de Beer, M. P., van der Laan, H. L., Cole, M. A., Whelan, R. J., Burns, M. A., Scott, T. F. Rapid,
continuous additive manufacturing by volumetric polymerization inhibition patterning, Sci
Adv, 2019, 5(1), eaau8723.
[15] Tumbleston, J. R., Shirvanyants, D., Ermoshkin, N., Janusziewicz, R., Johnson, A. R., Kelly, D.,
Chen, K., Pinschmidt, R., Rolland, J. P., Ermoshkin, A., Samulski, E. T., DeSimone,
J. M. Continuous liquid interface production of 3D objects, Science, 2015, 347(6228),
1349–1352.
[16] Deng, S., Wu, J., Dickey, M. D., Zhao, Q., Xie, T. Rapid open-air digital light 3D printing of
thermoplastic polymer, Adv Mater, 2019, 31(39), 1903970.
[17] Janusziewicz, R., Tumbleston, J. R., Quintanilla, A. L., Mecham, S. J., DeSimone,
J. M. Layerless fabrication with continuous liquid interface production, PNAS, 2016, 113(42),
11703–11708.
[18] Walker, D. A., Hedrick, J. L., Mirkin, C. A. Rapid, large-volume, thermally controlled 3D
printing using a mobile liquid interface, Science, 2019, 366(6463), 360–364.
[19] Kelly, B. E., Bhattacharya, I., Heidari, H., Shusteff, M., Spadaccini, C. M., Taylor,
H. K. Volumetric additive manufacturing via tomographic reconstruction, Science, 2019,
363(6431), 1075–1079.
[20] Hart, A. J., Rao, A. How to print a 3D object all at once, Science, 2019, 363(6431), 1042–1043.
[21] Loterie, D., Delrot, P., Moser, C. High-resolution tomographic volumetric additive
manufacturing, Nat Commun, 2020, 11(1), 852.
[22] Norman, J., Madurawe, R. D., Moore, C. M. V., Khan, M. A., Khairuzzaman, A. A new chapter in
pharmaceutical manufacturing: 3D-printed drug products, Adv Drug Deliv Rev, 2017, 108,
39–50.
[23] Sun, Y., Soh, S. Printing tablets with fully customizable release profiles for personalized
medicine, Adv Mater, 2015, 27(47), 7847–7853.
[24] Liang, K., Carmone, S., Brambilla, D., Leroux, J.-C. 3D printing of a wearable personalized oral
delivery device: A first-in-human study, Sci Adv, 2018, 4(5), eaat2544.
[25] Murphy, S. V., De Coppi, P., Atala, A. Opportunities and challenges of translational 3D
bioprinting, Nat Biomed Eng, 2020, 4, 370–380.
[26] Kang, H.-W., Lee, S. J., Ko, I. K., Kengla, C., Yoo, J. J., Atala, A. A 3D bioprinting system to
produce human-scale tissue constructs with structural integrity, Nat Biotechnol, 2016,
34(3), 312–319.
[27] Moroni, L., Burdick, J. A., Highley, C., Lee, S. J., Morimoto, Y., Takeuchi, S., Yoo,
J. J. Biofabrication strategies for 3D in vitro models and regenerative medicine, Nat Rev
Mater, 2018, 3(5), 21–37.
[28] Giannopoulos, A. A., Mitsouras, D., Yoo, S.-J., Liu, P. P., Chatzizisis, Y. S., Rybicki,
F. J. Applications of 3D printing in cardiovascular diseases, Nat Rev Cardiol, 2016, 13(12),
701–718.
[29] Kim, S. H., Yeon, Y. K., Lee, J. M., Chao, J. R., Lee, Y. J., Seo, Y. B., Sultan, M. T., Lee, O. J., Lee,
J. S., Yoon, S.-I., Hong, I.-S., Khang, G., Lee, S. J., Yoo, J. J., Park, C. H. Precisely printable and
biocompatible silk fibroin bioink for digital light processing 3D printing, Nat Commun, 2018,
9(1), 1620.
[30] Noor, N., Shapira, A., Edri, R., Gal, I., Wertheim, L., Dvir, T. 3D printing of personalized thick
and perfusable cardiac patches and hearts, Adv Sci, 2019, 6(11), 1900344.
 Chapter 10 Main challenges in 3D printing 333

[31] Lee, A., Hudson, A. R., Shiwarski, D. J., Tashman, J. W., Hinton, T. J., Yerneni, S., Bliley, J. M.,
Campbell, P. G., Feinberg, A. W. 3D bioprinting of collagen to rebuild components of the
human heart, Science, 2019, 365(6452), 482–487.
[32] Hinton, T. J., Jallerat, Q., Palchesko, R. N., Park, J. H., Grodzicki, M. S., Shue, H.-J.,
Ramadan, M. H., Hudson, A. R., Feinberg, A. W. Three-dimensional printing of complex
biological structures by freeform reversible embedding of suspended hydrogels, Sci Adv,
2015, 1(9), e1500758.
[33] Grigoryan, B., Paulsen, S. J., Corbett, D. C., Sazer, D. W., Fortin, C. L., Zaita, A. J., Greenfield,
P. T., Calafat, N. J., Gounley, J. P., Ta, A. H., Johansson, F., Randles, A., Rosenkrantz, J. E.,
Louis-Rosenberg, J. D., Galie, P. A., Stevens, K. R., Miller, J. S. Multivascular networks and
functional intravascular topologies within biocompatible hydrogels, science, 2019,
364(6439), 458–464.
[34] Dasgupta, Q., Black, L. D. A FRESH SLATE for 3D bioprinting, Science, 2019, 365(6452),
446–447.
[35] Koffler, J., Zhu, W., Qu, X., Platoshyn, O., Dulin, J. N., Brock, J., Graham, L., Lu, P., Sakamoto,
J., Marsala, M., Chen, S., Tuszynski, M. H. Biomimetic 3D-printed scaffolds for spinal cord
injury repair, Nat Med, 2019, 25(2), 263–269.
[36] Johnson, A. R., Tumbleston, J. R., Bloomquist, C. J., Moga, K. A., Ermoshkin, A., et al. Single-
step fabrication of computationally designed microneedles by continuous liquid interface
production, PLoS ONE, 2016, 11(9), e0162518.
[37] Lim, S. H., Kathuria, H., Tan, J. J. Y., Kang, L. 3D printed drug delivery and testing systems – a
passing fad or the future?, Adv Drug Deliv Rev, 2018, 132, 139–168.
[38] Bernal, P. N., Delrot, P., Loterie, D., Li, Y., Malda, J., Moser, C., Levato, R. Volumetric
bioprinting of complex living-tissue constructs within seconds, Adv Mater, 2019, 31(42),
1904209.
[39] Layani, M., Wang, X., Magdassi, S. Novel materials for 3D printing by photopolymerization,
Adv Mater, 2018, 30(41), 1706344.
Index
(mercaptopropyl)methylsiloxane 162 biomedicine 281
(meth)acrylated chitosan 184 bisphenol A 147
(meth)acrylated poly(ethylene glycol) 178 blood-brain barrier 283
“dynamic” caging 281 blue light 6, 23
2-nitrophenyl phenyl sulfide 152 bone regeneration 189
3D helical mircorobots 273 bottom-up 250
3D printing 6, 11, 17, 20, 24, 29, 33, 35, 37, butyl nitrite 141
231–232, 239, 241–242, 245, 295–298, butylated hydroxytoluene 153
303–308
3D printing and microfabrication 83 CAD. See computer-aided design
405 nm 232, 241, 245 CAL 330
4-acryloylmorpholine (ACMO) 318 camphorquinone 141, 151
4D printing 296, 320 capacitors 284
800-nm infrared 40 carbazole 12
– other carbazole 14
absorber. See photo-blocker – oxime-esters 12
accuracy 254 carbon nanotubes 283
acrylate 144–149, 153–154, 161 cardiomyocytes 329
additive manufacturing 203, 213–214, 226, 249 cardoimyocytes (CMs) 328
AMF file 136 cartilage regeneration 193
analytical devices 143 cationic 232, 236–237, 243–244
anthracene 152 cationic resins 146
anthraquinone cell culture 283
– 15-DAAQ 32 cell engineering 281
application 206, 208, 212, 216–217, 219–221 cell fixation 281
applications 189 cell migration 281
aspect ratio 254 cell stimulation 285
ASTM 135 ceramic particles 162
attenuation coefficient 154–156 ceramics 269, 286
average photon flux intensity 255 chain inhibition 252
chain reaction 252
chain transfer 252
barium titanate NPs 285
charge transfer 283
beam shaping 265
chemical stability 161–162, 164
Beer-Lambert law 154
chiral 277
benzil ketals 151
cholesteric liquid crystals 287
benzoin 151
CLIP. See continuous light interface production
benzophenone 151
clobetasol propionate (CBS) 324
benzotriazole 152
color microactuators 287
benzyl-N,N’-dimethylamine 153
Composite materials 84
beyond diffraction limit 250
computed axial lithography (CAL) 323
binder jetting (BJ) 320
computed axial lithography 141
bio-applications 273
computed tomography (CT), 323
Biological 83
computed tomography 141
biomaterials 145
computer-aided design (CAD) 317
biomedical 281
computer-aided design 136, 143–144

https://doi.org/10.1515/9783110570588-011
336 Index

conductive 283 energy conversion 252

continuing scanning 254 epoxide 147–148
continuing scanning mode 257 epoxy group 267
continuous light interface production 140 epoxy resins 146
continuous liquid interface production 212 ethyl 4-(dimethylamino) benzoate 141
continuous liquid interface production (CLIP) 320 extracellular matrix 187
coumarin 52
CP 25–26, 31 feature size 254
critical conversion 155–156 femtosecond direct laser writing (fs-DLW)
critical energy 156 – fs-DLW 249
CT 328 fillers 153
CTC 17, 30 flavone
– amine 17 – 3HF 2, 4
– amine-iodonium 17 – 6HF 2, 4
– phenylamine 17 – 7HF 2
– phosphine 21 – chrysin 2
cure depth 33 – myricetin 2, 4
curing time 155 fluorene 54
fluorinated oil 322
dead zone 140, 320, 323 Fluoropor 163
degenerative exchange 303–304 fractional conversion 154
degraded free radical 150
– biodegradable 281 free radical polymerization 252
dental resin 5, 23, 31 freeform reversible embedding of suspended
diameter 255 hydrogels (FRESH) 329
differentiation frontal polymerization 155
– cell differentiation 285 FRP 26, 30
digital light processing 138, 208 fs-DLW 249
digital light projection (DLP) 318 full width at half maximum 257
digital mirror device 139 functional oxides photoresist 271
diluents 152 functionalities 295–296, 304–305, 308
DLP 319–320, 326–327 fused deposition modeling (FDM) 135, 161, 324
dormant 295, 298, 303, 308
drug delivery 281 galvanometer 137–138
drug delivery systems 197 gel point 148, 150, 154
dual-response 287 gelation 153
dye glass transition temperature 146, 148
– dyes 107–108, 110–111, 113–115, 118–128 glycidyl methacrylate (GMA) 326
D-π-A-π-D 52 green light 22, 26

elasto-mechanical unfeelability cloaks 277 HARP 323

elastomers 145 HAuCl4 285
electrodeless reduction 283 hierarchical parallel manufacturing 266
electron donating group high reaction rate 252
– EDG 12, 19, 26 high refractive index 285
electron transfer 252 high-area rapid printing (HARP) 322
electron withdrawing group HOMO 19
– EWG 12, 19, 26 HOMO-LUMO gap 19
endothelial cells (ECs) 328 Hull, Charles 136, 144
 Index 337

humidity-responsive 279 metal 22

hybrid composites 269 – Cu(I) complex 25
hydrogel 36 – ruthenium complex 24
hydrogels 271 – ZnTPP 22
hydrogen atom transfer 151 methacrylate 144–146, 153
hydroxyacetophenone 151 – perfluoropolyether 162
hydroxyethyl methacrylate 162 methacrylated alginate 185
methacrylated bovine serum albumin 182
improve printing speed 264 methacrylated collagen 181
improvement of resolution 257 methacrylated poly(vinyl alcohol) 179
induction time 155–156 methacrylated polycaprolactone 178
inhibition 137, 146, 148, 154 methacrylated silk fibroin (Sil-MA) 326
inhibition volume 322 methoxy hydroquinone 153
inhibitors 152 methyl ethyl hydroquinone 144
initial stages 257 methylsilsesquioxane 162
integrated tissue–organ printer Michael addition 148
(ITPO) 326 microfluidics 135, 143, 157–158, 162–164
interfacial solvent polarity 279 – channel dimensions 143, 164
iodonium salts 147 – electrophoresis 164
iquid crystal display 209 – gradient generator 163–164
isopropylthioxanthone 165 – integrated device 167
isotropic stiffness 277 – isotachophoresis 164
– micromixing 164
Jacobs curve 156 – modular devices 167
– optical detection 144, 164
laminated object manufacturing 135 – PDMS 164–165
laser stereolithography. See SLA microscale continuous projection printing
layer by layer 305 (μCPP) 330
layer print time 158 microscope objective
layer thickness 155–156, 158 – to tightly focus laser beam 253
layer-by-layer 295, 304, 308 microswimmers 281
layer-by-layer printing 143 migration
layerless printing 140 – cell migration 281
length 255 mircogripper 279
light dose 158 modifications 295, 304
light intensity 154 modified BAPO
light penetration 8, 33 – CNC-BAPO 38
light-responsive 279 – PEG-BAPO 38
liquid chromatography 162 modified hydrogels 273
liquid crystal display 210 molar absorption coefficient 154
liquid crystals 279 monomer functionality 155
liquid photosensitive resins 204, 206 monomer radicals 252
Lithography 91 monomers 204
LUMO 19 motion system 253
multi-focus parallel processing 264
mechanical metamaterials 277 multihyroxy 4
mechanical properties 146, 149–150, 158, 161 multi-jet printing 211
mechanisms 295–296, 301, 308 multi-material printing 136, 143, 167
MEMS 279, 283 multi-photon absorption 250
338 Index

multiple foci 265 pentaerythritoltetrakis

multiple-beam interferometry 264 (3-mercaptopropionate) 148
multiwalled carbon nanotubes 284 personalized bioink 328
personalized medicine 323
nano particles 273 PET-RAFT 299–302, 305–306, 308
nanopillar diffraction gratings 286 PH
natural 2 – PH-resposive 279
– coumarin 6 phenylamine
– flavone 2 – NPG 17
natural hydrogels 271 photoabsorber 110, 118–119
neural 283 – photoabsorbers 110, 113, 118, 120
neuronal repair 196 photoactivation 298–299, 301
node geometry 277 photoactive cellulose 186
nonlinear condition 256 photoactive gelatin 180
non-radiation state 250 photoactive hyaluronic acid 185
NPG 4, 10 photo-blocker 137, 144, 151, 153–154,
nucleation site 283 157–158, 167
photocleavage 60
observation photocuring 3D printing 203–204
– cell observation 283 photocuring 231–232, 239, 243
oligomers 204 photoinhibition 322
optical 285 photoiniferters 299–301, 305
Optical materials 89 photoinitiation 322
optical model 158 photoinitiator 137, 144, 149, 153–154, 157,
optical tunable 286 162, 167
optical vortices 285 – cationic 147
organic polymers 267 – Type I 148, 150–151
organic-inorganic photoresist 269 – Type II 150–151
ORMOCER 269 photoinitiators 176, 204, 251
orthogonal 232, 234–235, 239–242, 244 photon flux intensity 254
others photonic 285
– acridone 30 photonic band gap 286
– anthraquinone 32 photonic crystal 286
– dithienophosphole 31 photonic crystals 286
– modified BAPO 35 photopolymerization 157, 203–207, 209,
– naphthalimide 26 215–217, 231–232, 234, 236, 238, 241,
– safranine O 33 244–245, 295–297, 304–306, 308
– semiconductor-metal hybrid nanoparticle 38 – kinetics 153, 156
– triazine 34 – rate 153–154
overcuring 152, 158 photopolymers 177
oxygen 296–297, 305, 307, 309 photoRAFT 295–296, 298, 300–301, 303, 305, 309
oxygen diffusion 6, 15 photoredox catalysts 301, 305, 307
oxygen inhibition 24 photoresist 267
oxygen permeable window 322 piezoelectric 285
oxygen tolerant 301, 307–308 pinpoint scanning mode 257
pinpointing scanning 254
PDMS 144 PLA 324
PEGDA 145, 159 poly (propylene fumarate) 180
penetration depth 151–153, 156 poly(L-lactic acid) (PLA) 324
 Index 339

poly(vinyl alcohol) (PVA) 324 selective laser sintering 135

poly(ε-caprolactone) (PCL) 326 selective laser sintering (SLS) 320
polydimethylsiloxane. See PDMS separation science 162
polyethylene glycol diacrylate. See PEGDA sequential absorption 250
polymer crosslinked networks 295, 298, shape cells 281
301, 304 shape-memory polymers 145
polymeric crosslinked networks 303 shrinkage 147–148
polymerization depth 157 silica nanoparticles 162
polytetrafluoroethylene 162 Sil-MA 327
postpolymerization 298, 304 simultaneous absorption 250
postprinting 296, 305, 308 single walled carbon nanotubes 283
postprinting modification 296, 305, 307–308 single-photon absorption 250
precursors 178 skin regeneration 193
preserved 296, 304–305, 308 SLA 135–136, 143, 157, 161, 320
printing efficiency 264 – advantages and disadvantages 143
process parameters 257 – bottom-up configuration 137, 139
PTFE. See polytetrafluoroethylene – glass 164
pyrene 152 – materials 161
pyrogallol 153 – PDMS 164
pyrolysis 269 – top-down configuration 137
sodium persulfate 24
quenching effect 259 software 254
quenching effect. 259 sol-gel 271
quenching process 258–259 SOLIDWORKS 136
solvent stability 143
radical 232, 234, 236–238, 241, 243–244 soy protein isolate 184
radical polarizer 285 space-time focusing technique 264
radical scavenger 4 spatial light modulator 265
RAFT agents 296, 298–300, 303–305, 308 spatial light modulators 264
RAFT polymerization 298–299, 301–302, spinal cord 330
304–306, 308 spiral phase 285
Rayleigh length 255 SR400 267
reactivatable species 296, 308 stabilizer 137
relative speed 264 stereo lithography Apparatus 207
renal/liver tissue repair 196 stereolithographic apparatus for tissue
resins 136, 144 engineering (SLATE) 329
– composites 162 stereolithography (SLA) 317
– dual-cure 148 stereolithography. See SLA
– optical model 158 stimulated emission depletion microscopy
– thiol-ene 148–149, 154 – STED 260
– thiol-yne 148–149 STL file 136
resistors 284 SU-8 267, 285
ring-opening addition 267 subdiffraction-limit resolution 252
rules for choosing photoinitiators 260 sub-threshold 257
Sudan Orange 152
scaffold 283 sulfonium salts 68
scanning galvanometer 265 supernatural phenomena 265
Schiff bases 52 superparamagnetic 281
SCR368 267 surface roughness 139
340 Index

surface-eroding polymer 324 two-photon lithography (TPL)

synthetic hydrogels 273 – TPL 249
two-photon polymerization 49
tailored bandgap 285 – TPP 249
temperature and light respond 279 Two-photon sensitizers 70
the finite element simulation 277
thermal stability 162 ultrafast laser 253
thiocarbonylthio 298, 300–301, 304 ultrafast shutter 254
thioxanthone 151 under air 5, 23, 26
tissue engineering 283 urethane acrylate 267
titania photoresist 271 urethane diacrylate 144
TPA cross-section 250 urethane dimethacrylate 145
TPL 249–250 UV 6, 12, 26, 233–234, 238–242, 244–245
triazine 33
triethylene glycol dimethacrylate 145 vanillic acid (VA) 324
trimethylolpropane triacrylate 146, 156 vascularized tissues 195
trimethylolpropanetris vinylmethoxysiloxane 162
(3-mercaptopropionate) 148 virtual state 250
tris[2-(3-mercaptopropionyloxy)ethyl] viscosity 146, 150, 152
isocyanurate 148 visible light 30, 234, 238–240, 242, 244, 297,
trithiocarbonate 300, 303 300, 304, 306
TTC 300, 303–305, 308 vitrification 150
TTCs 303–306 volumetric photopolymerization 141
tubular organs and tissues 326
two-order nonlinear optical absorption 250 water soluble 71
two-photon 3D printing 212 water-soluble PI 28
two-photon 12, 38 wavelength 231–241, 243–245
– HAPI 40
– oxime-esters 40 Young’s modulus 146, 148
– z-scan 12
two-photon absorption (TPA) 250 Zr-containing acrylic photoresist 271
Two-photon absorption 49, 249 z-resolution 137, 152
Two-photon cationic photoinitiators 68
Two-photon free-radical photoinitiator 51
α-cleavage 150