RECENT ADVANCES

Prof Dr. S.M. Tahir

FCPS
Muhammad Medical College
Mirpurkhas

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 RECENT ADVANCES

 In USA, 450,000 pts require medical

treatment annually.
 45,000 admissions to hospitals
 3500 deaths.
 Impact is much greater in developing

countries.
 In India (population over 1 billion) 700,000

cases of burns are hospitalized every year.

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 RECENT ADVANCES

 Systemic review by Kendrick in year 2010.

 Incidence is 315/100,000.
 (remarkably in contrast to USA 19/100,000)
 50% are young patients.
 25% are between age 0-5 years.
 Hospital mortality is 20-38 % .

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 RECENT ADVANCES6

 ACELLULAR SKIN SUBSTITUTES

◦ Biobrane®
◦ Integra®
◦ Alloderm®
 CELLULAR ALLOGENIC SKIN SUBSTITUTES
◦ Transcyte®
◦ Dermagraft®
◦ Apligraf® (Graftskin®)
 CELLULAR AUTOLOGOUS SKIN SUBSTITUTES
◦ Cultured Epidermal Autograft (CEA)
◦ Cultured /Engineered Skin Substitutes (CSS/ESS)

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 RECENT ADVANCES

 Started in 1970.
 Now most widely used SS.
 Made of nylon mesh, which acts as a “dermis” and a
silicon membrane which acts as an “epidermis”.
Both are embedded in pig collagen.
 It is mainly used as a temporary coverage for
 Superficial/mid-dermal burns.
 Wound.
 Donor site.

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 RECENT ADVANCES

 Advantages:
◦ Readily available, (Not in Pakistan)
◦ Low pain,
◦ Shorten hospital admission time,
◦ Accelerated wound healing, and
◦ Useful adjuvant to Buy time until skin graft material
is available.

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 RECENT ADVANCES

 Disadvantages:
◦ Exudates collected beneath biobrane makes patient
prone to infection.
◦ Few reported cases of toxic shock.
◦ Uses Pig collagen and therefore not accepted in our
country .

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RECENT ADVANCES

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 (a) An extensively blistered burn wound . (b)meticulously cleaned
 (c) @ day 9 Biobrane glove has been (d) excellent healing
 applied .
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 RECENT ADVANCES

 Pioneered by Yannas and Burke.

 It is a bi-layered skin , impermeable to

water
 Epidermal layer is a silicone

membrane.
 The dermal part is made of bovine

collagen and shark chondroitin-6-

sulphate glycosaminoglycan.

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 After coverage, the wound
becomes revascularized within 2-
3 weeks.
 Once fully vascularized, the

superficial silicone layer is

removed and replaced by a very
thin split skin graft onto the neo-
dermis bed.
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 RECENT ADVANCES

 Advantages:

◦ Immediate availability,
◦ Allowing time for the neo-dermis
formation, and
◦ Good aesthetic results.
 Disadvantages :
◦ Two-step.
◦ Expensive, and
◦ Infection (exudate collection underneath).
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 Integra is supplied
with outer Tyvek
pouch.
 Aluminum foil
pouch is opened.
 INTEGRA® is
packaged between
2 polyethylene
sheets and an
attached center tab.
 By holding tab,
gently peel off one
of the polyethylene
sheets

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 Gently peel off the
other polyethylene
sheet
 By holding tab,
placed into a basin
containing the
sterile saline
solution and
carefully remove
INTEGRA® from the
tab.
 Rinse INTEGRA®  for
1-2 minutes
 Integra Can be
meshed to 1:1, with
non crushing
mesher without
using instruments.

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  INTEGRA® Dermal
Regeneration
Template is
scooped
from from the
holding basin with
gloved hands and
place directly onto
the wound.
 The silicone side
is facing up and
the Collagen-GAG
matrix is against
the wound bed.
The black thread
identifies the
silicone side.

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 RECENT ADVANCES

 This is formed from acellular matrix derived from

a cadaveric dermis.
 The allodermis is processed by salt to remove the
epidermis and then extracted with a solution to
remove any cellular material.
 Freeze-dried to render it inert immunologically.
 AlloDerm supports tissue regeneration by
allowing rapid revascularization, white cell
migration and cell population - ultimately being
transformed into host tissue for a strong, natural
repair.

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 RECENT ADVANCES

 Although its basement membrane remains

intact but It has no epidermal layer.
 Yet this acellular matrix provides a good

natural medium for fibroblast and

endothelial cells to regenerate from the neo­
dermis.
 Widely used in breast Reconstruction and

dental surgery.

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 Alloderm is
usually used as
sling to
support implant
 and cover the
anterior surface
of the implant.

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 RECENT ADVANCES

 The Transcyte® tissue engineered skin substitute

is made from a nylon mesh and a silastic semi
permissible and biocompatible layer.
 Allogenic fibroblasts from neonatal foreskin are
embedded in the mesh and allowed to grow for
3-6 weeks to produce a cellular matrix of
collagen and growth factors which may enhance
wound healing.
 It is left in place until either spontaneous
separation occurs which indicates wound bed
healing or the wound is dealt with surgically.
 It has been licensed by the FDA for use in burns.

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 TransCyte is a
temporary
cover made
from artificial
skin, which
promotes
faster healing
in burn
patients.

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 RECENT ADVANCES

 The Dermagraft® skin substitute is similar to

Transcyte® but
 It lacks the silicone layer and
 Contains viable fibroblasts.
 It is produced by mixing living neonatal

foreskin fibroblasts with a polyglycolic acid

mesh (Dexon or Vicryl).

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 RECENT ADVANCES

 The fibroblasts are cryopreserved at -80°C to

maintain viability and when implanted to the
wound, these start to proliferate and produce
a variety of growth factors and extracellular
collagen matrix components.
  The polyglycolic acid mesh is absorbed

within 3-4 weeks.

 It has been used effectively in Diabetic foot

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RECENT ADVANCES

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 RECENT ADVANCES

The FDA approved it for clinical use in 1998

for the treatment of venous ulcers or
neuropathic diabetic ulcers.
 It has both living dermis and epidermis and

therefore example of “skin equivalent’ or

“organo-typical skin substitute” .

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 RECENT ADVANCES

 It is prepared by mixing living fibroblasts

from neonatal foreskin with bovine collagen
type I and then exposing them to heat to
produce a loose matrix left for 2 weeks to
allow formation of new collagen and matrix
resulting in dense fibrous network.
 A suspension of living neonatal foreskin
keratinocytes (from the same or different
neonatal donor) is seeded on the surface of
the dermal fibrous matrix and left for 4 days
to proliferate and differentiate.

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 RECENT ADVANCES

 On the last two days, the calcium

concentration is increase in the culture
medium and the keratinocytes are raised to a
liquid air interface to allow differentiation and
stratum corneum formation for 7-10 days.
 At this stage, it is ready for clinical use

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 RECENT ADVANCES

 Licensed indication are (not responding to

other measures)
◦ Diabetic and
◦ Venous ulcer
 It is also used to manage wounds in
◦ Epidermolysis bullosa,
◦ Donor sites,
◦ Surgical excision of skin cancer and
◦ Burns.

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 Apligraft is being
Apligraft as supplied Remove from package
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FENESTRATE MESH

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Staple
Steri Strip
Skin glue.
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 RECENT ADVANCES

 The technique of cells culture was originally

developed by Rheinwald and Green

 This Skin substitute is used when we need

permanent skin coverage by cultured
autologous keratinocytes.

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 RECENT ADVANCES

 Skin biopsy is taken from the patient.

 Dermis and subcutaneous tissue are

removed.
 The remaining epidermis is minced with mice

fibroblast which is already lethally irradiated

using 3T3.
 Allow to grow 4-5 weeks using culture

medium containing essential elements

including epidermal growth factors

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 RECENT ADVANCES

 Cultured keratinocytes are difficult to

handle and therefore they need a
delivery system or a supporting
dressing.
 Commercially available CEA vary in

delivery system and supporting

dressing.

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Application of Cultured Cultured Epidermal Autografts
Epidermal Autografts Applied to the Hand and Arm

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 RECENT ADVANCES

 Clinically, the problem associated with the

use of Keratinocytes are due to poorly
developed dermo-epidemal junction and
include.
 Blisters formation following small amounts

of friction since the dermal epidermal

junction is not completely developed.
 Scarring,
 contracture and
 Hyperkeratosis. 

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 RECENT ADVANCES

 Average Take rate is usually 30-80%.

 However it is unpredictable and ranges from

0% to 100%.

 CEA is susceptible to digestion by

collagenase enzymes present in the wound
bed.

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 It has both epidermal and dermal
components.
 It is an autologous graft, therefore the risk

of infection transmission is minimum.

 It provides permanent coverage.
 Several types were developed recently with

different dermal biosynthetic scaffolds.

 The most commonly used type is a

hyaluronic acid derived substitute.

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 RECENT ADVANCES

 Hyaluronic acid (Hyaluronan) is a naturally

occurring polymer within the skin and it has
been found to be pro-angiogenic thus
stimulating blood vessel growth.
 It was found first in the vitreous humor of

the eye in 1934 and subsequently

synthesized in vitro in 1964.

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 RECENT ADVANCES

 Hyaluronic acid facilitates the

◦ Growth and movement of fibroblasts,
◦ Controls matrix hydration and
◦ Osmoregulation.
◦ It is also a free radical scavenger and
an inflammatory regulator.

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RECENT ADVANCES

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