See discussions, stats, and author profiles for this publication at: https://www.researchgate.

net/publication/334169930

ANIMAL MODELS IN MODERN BIOMEDICAL RESEARCH

Article  in  EUROPEAN JOURNAL OF PHARMACEUTICAL AND MEDICAL RESEARCH · July 2019

CITATIONS READS

2 1,629

5 authors, including:

Belma Pehlivanovic Nermina Ziga Smajic

University of Sarajevo University of Sarajevo
19 PUBLICATIONS   6 CITATIONS    21 PUBLICATIONS   14 CITATIONS   

SEE PROFILE SEE PROFILE

Some of the authors of this publication are also working on these related projects:

Implementong the calculation of appropriate drug dose for children using the programming language C# View project

All content following this page was uploaded by Belma Pehlivanovic on 02 July 2019.

The user has requested enhancement of the downloaded file.

 ejpmr, 2019,6(7), 35-38 SJIF Impact Factor 4.897
EUROPEAN JOURNAL OF PHARMACEUTICAL Review Article
Pehlivanović et al. European Journal of Pharmaceutical and Medical Research
AND MEDICAL RESEARCH ISSN 2394-3211
www.ejpmr.com EJPMR

ANIMAL MODELS IN MODERN BIOMEDICAL RESEARCH

Pehlivanović Belma*, Fetahović Dina, Aruković Emina, Žiga Nermina and Bečić Fahir

Faculty of Pharmacy, University of Sarajevo, Zmaja od Bosne 8, Sarajevo, Bosnia and Herzegovina.

*Corresponding Author: Pehlivanović Belma, MPharm

Faculty of Pharmacy, University of Sarajevo, Zmaja od Bosne 8, Sarajevo, Bosnia and Herzegovina.

Article Received on 30/04/2019 Article Revised on 20/05/2019 Article Accepted on 10/06/2019

ABSTRACT
Animal models represent unique source of in vivo data for various fields of biomedical research. In today’s
pharmaceutical drug development, animal models are used as pre-clinical tools for potential drug screening process
and translation into clinical trials. These models are most commonly used as in vivo models for evaluation of basic
pharmacokinetic parameters, drug efficiency and safety. Selection of ideal animal model for biomedical research is
crucial part of research process as there are important parameters that researcher have to have in mind when
selecting animals for their trials. In field of tissue engineering very important contribution is given by usage of
various animal models. For in vivo testing of medical devices a variety of animal species can be used to define a
model. This is important in gathering preliminary information on the safety and, in some cases, effectiveness of a
device. This review describes application of animal models in different fields of biomedical research, such as drug
and medical devices development, and hopes to summarize main properties needed for selection of ideal animal
model in biomedical research.

KEYWORDS: Animal models, animal use, biomedical research.

INTRODUCTION advantage in selection criteria as well as their availability

Over past decades, significant contribution in area of in multiple sub-species.[1] The recent development in
biomedicine, drug development and preclinical trials biomedical research has created animal models very
have been made by application of different animal specific to the needs of individual research project, such
models. Not only such models are responsible for better as transgenic models which can be defined as animals
understanding of various physiological processes, made by adding foreign genetic information to the
therapy outcomes and drug safety but they have nucleus of embryonic cells, thereby inhibiting gene
contributed in novel aspects of medical devices expression. This can be accomplished either by injecting
development and tissues engineering. the foreign DNA directly into the embryo or by using a
retroviral vector to insert the trans-gene into
Selection of ideal animal model for biomedical research an organism's DNA.[2] Transgenic animals are unique
is crucial part of research process that involves usage of models that are custom made with specific biological
animal models, as not all animal models are applicable characteristics. Therefore, the ability to induce functional
for biomedical research due to wide range of limitations. genes into animals provides a powerful tool for studying
There are many parameters that researcher have to have complex biological processes.[2][3]
in mind when selecting ideal animal model for their
trials. The most important parameter in general selection For identification of new models, genetic screening and
is resemblance between animal species and humans on characterization of chance mutations remain a long and
physiological and pathophysiological levels, their tough task. Moreover, classical genetic monitoring
response on certain substances/drugs and their ability to cannot appositely engineer a specific genetic trait in a
reproduce the disease or condition that is examined. Not directed fashion.[3] The gene transfer technology that is
less important criteria are the size and availability of currently utilized, was introduced using mouse and
animal species. It is not common to use rare animal domestic animal models. Today, the mouse is still
species for research, as models should be easily available serving as a starting point for implementing a gene
so that further validation and repetition of research can transfer procedures and is the standard for optimizing
be done, or to use animal species that aren’t large enough experimental efficiencies for many species.
for multiple sampling (blood, tissues etc.). Another
significant parameter is the life duration of specie, as Careful selection of a model is frequently associated with
they have to survive long enough for results to be a nature of the drug to be tested. Often, a human disease
meaningful. Sufficiently robust animal models have cannot be signified by a specific animal model. In this

www.ejpmr.com 35
Pehlivanović et al. European Journal of Pharmaceutical and Medical Research

way, association of several animal models will provide a animal models. At the beginning of tissue engineering
better insight towards mechanisms of action of a research processes most popular animals used were dogs,
particular pharmaceutical agent.[4] Over the years various but due to ethical aspects and popularity of dogs as
experimental animal models, such as yeasts, zebra fish “home pets” their use in biomedical research has been
and fruit flies were developed for research, on which a significantly reduced. Nowadays, most popular animal
huge amount of information has been collected. models for various tissue engineering applications are
rats. Although limitations of rats are well known and
ANIMAL MODELS IN PHARMACEUTICAL they reduce their use and reliability, rats have most
DRUG DEVELOPMENT similar physiology and complexity to humans which
In today’s pharmaceutical drug development, animal makes them first choice in various biomedical research
models are used as pre-clinical tools for potential drug processes. Rats serve as a practical and reproducible
screening process and translation into clinical trials. model in tissue engineering but jet there are many
Animal models are most commonly used in vivo models biochemical and physiological differences between them
for evaluation of basic pharmacokinetic parameters, drug and humans.[8]
efficiency and safety. Furthermore, they are used for
different preclinical testing that include general and Lately, scientist that are involved in tissue engineering
specific study of toxicity, because data of preclinical and regenerative medicine are searching for models and
safety and efficacy is needed for submission to drug methods to treat different classes of bone malignancies
regulatory agencies before continuing to perform further by developing model that posses clinical manifestation of
studies in humans. One of the most important steps in disease. Large animals, such as sheep and pigs, have
drug development is preclinical toxicology test that been used for determination of bone formation and
involves using a high number of animals. These tests projection of similarities to human cases of disease. Use
include exploration of general toxicity, eye and skin of large animals in this field of biomedical research has
irritancy, mutagenicity, carcinogenicity and its advantages such as physiological and size similarities
teratogenicity. Animals that are usually used in this humans, but problem of increasing their use and
toxicity studies are rodents (mice, rats) and non-rodents acceptance in biomedical research is still a burning issue.
(rabbit). Very often correlation of in vitro and in vivo In the other hand, smaller animals such as rodents, have
models is determined so that biomedical research can been used for evaluation of bone regeneration and
proceed into clinical trial. similarities in bone malignancy, and their application in
scientific purposes raise less ethical concerns.[8][9]
Pre-clinical trials in drug development, which involves
animal models, have certain stages that have to prove Furthermore, injury models are very useful for
that potential drug will reveal expected therapeutic understanding and predicting physiological and
effects. If in early stages of trials drug demonstrates therapeutic outcomes that are used in various fields of
desirable results, only then further studies will be carried regenerative and tissues engineering.
out. Potential new drug that seem to have a promising
results of being effective and safe from this pre-clinical Critical size bone defects are a good example of an
trials on animals will be then tested in small groups of injury model and how it’s affected by the species and age
human volunteers, while further animal testing continues of the animal being used, showing us that it is not just the
at the same time in order to examine the effects when a choice of a particular species that is important, but also
drug is taken for a long time.[4][5] Most of animal studies their development stage. Naturally occurring disease
in drug development use rodents, mainly mice and rats, models in species such as horses or dogs give a chance to
because it is shown that this species have very big treat human-like disease that precisely reflect the lesion
biological similarity with humans. One of the advantages heterogeneity of human populations. These animal
is that rodents are relatively small and easy to keep models are rarely used because of their cost and
healthy in well-designed laboratories.[6] Their natural accessibility, but working with them gives a rare
duration of life is short, so the explore can quickly get opportunity to speed development of treatments for
information on their long-term health. New regulatory human disorders.[9]
guidelines require that new medicine needs to be tested
on two different types of animals, one a non-rodent such ANIMAL MODELS IN MEDICAL DEVICE
as a rabbit, dog or primate. In practice, 80% of all studies DEVELOPMENT
that include animals are performed on rodents. Very According to FDA a medical device is defined as "...an
small percentage involves dogs, primates or cats.[6][7] instrument, apparatus, implement, machine, contrivance,
implant, in vitro reagent, or other similar or related
ANIMAL MODELS IN TISSUE ENGINEERING article, including a component part, or accessory which
Animal models play crucial role in different fields of is: recognized in the official National Formulary, or the
tissue engineering. Various in vitro methods, such as cell United States Pharmacopoeia, or any supplement to
lines, have been used to develop new tissue engineering them, intended for use in the diagnosis of disease or
models, but determination of viability of tested tissue in other conditions, or in the cure, mitigation, treatment, or
living organisms have been investigated through use of prevention of disease, in man or animals, or intended to

www.ejpmr.com 36
Pehlivanović et al. European Journal of Pharmaceutical and Medical Research

affect the structure or any function of the body of man or living longer and healthier lives thanks to vaccines for
animals, and which does not achieve any of its primary rabies, parvovirus, tetanus and feline leukemia, among
intended purposes through chemical action within or on other breakthroughs made in Veterinary Medicine thanks
the body of man or animals and which is not dependent to animal research. Generally, research on mammals is
upon being metabolized for the achievement of any of its conducted on rat and mouse models, and to a lesser
primary intended purposes." There are 3 FDA regulatory degree on pigs and monkeys.[15]
classifications of medical devices: Class I, Class II and
Class III. The classifications are assigned by the risk that CONCLUSION
medical device presents to the patient and the level of Animal models are important in vivo tool of modern
regulatory control the FDA determines is needed to biomedical science and research. They have given great
legally market the device.[10] According to the way of contribution in different fields of pharmaceutical drug
their contact with the body, devices are divided as either development, preclinical testing and safety studies.
surface-contacting, external communicating, or Nowadays, ability of animal models to predict clinical
implantable. Surface-contacting devices come into outcomes are very high rated and future study designs
contact with the skin, mucous membranes, or have animal models as crucial parameters. The
compromised superficies (e.g. electrodes, skin tape, significance of animal models in medical device
contact lenses, orthodontic appliances, stomach tubes, development and tissue engineering are well described
and occlusive patches). External communicating devices and remains a task to define strict guidelines of proper
are either indirectly in contact to the blood path, usage and selection of animal models with regard to the
communicate directly with the tissue, bone or dentin, or 3Rs principles.
directly contact circulating blood (e.g. intravenous
administration sets, dental cement, skin staples, blood CONFLICT OF INTEREST
oxygenators and balloon catheters). Implantable devices The authors declare that they have no conflicts of
are those which are implanted into the body and directly interest.
contact either tissue, bone, or blood. Examples are:
ventricular assist devices, heart valves, vascular grafts, ACKNOWLEDGMENTS: None.
artificial joints, bone screws, and breast implants.[11][12]
REFERENCES
Preclinical testing includes testing of all materials and 1. Matthews RA. Medical progress depends on animal
prototypical devices before testing or using in humans. models - doesn’t it? J R Soc Med, 2008; 101: 95-8.
This testing is conducted in order to provide an assurance 2. Simmons D. The use of animal models in studying
of device safety prior to use in humans in a clinical trial. genetic disease: transgenesis and induced
It should be noted that, in some cases the animal testing mutation. Nature Education, 2008; 1(1): 70.
and in vitro testing may have satisfying regulatory 3. Perel P, Roberts I, Sena E, Wheble P, Briscoe C,
requirements for device approval. Preclinical testing Sandercock P, Macleod M, Mignini LE, Jayaram P,
includes in vitro and in vivo biocompatibility/ toxicity Khan KS. Comparison of treatment effects between
testing, ex vivo device testing, in vitro device testing, in animal experiments and clinical trials: systematic
vivo feasibility testing, and in vivo testing for safety.[9][10] review. BMJ, 2007; 334: 197.
4. Van Dam D, De Deyn PP. Animal models in the
For in vivo testing a variety of animal species can be drug discovery pipeline for Alzheimer’s disease. Br.
used to define a model. This is important in gathering J. Pharmacol, 2011; 164(4): 1285–1300.
preliminary information on the safety and, in some cases, 5. Badyal DK, Desai C. Animal use in pharmacology
effectiveness of a device. In vivo safety testing for education and research: the changing scenario.
regulatory submissions should be conducted in Indian J Pharmacol, 2014; 46(3): 257–265.
accordance with Good Laboratory Practices (GLP). 6. Fox JG, Barthold SW, Davisson MT, editors. , et al.
(Eds.) The Mouse in Biomedical Research.
Three sets of characteristic parameters influence animal Amsterdam: Elsevier, 2007.
model selection, during the development of a medical 7. Bloor CM, White FC, Roth DM. The pig as a model
device, and these are: the characteristics of the of myocardial ischemia and gradual coronary artery
biomaterial components, the characteristics of the device occlusion. In Swine as Models in Biomedical
design and the characteristics of the animal. In all cases, Research, Swindle MM, Ed., Iowa State University
the device and materials being evaluated should be Press, Ames IA, 1992; 163-175.
representative of the processes anticipated in the 8. Patrick C, Uthamanthil R, Beahm E, Frye C. Animal
manufacturing of the final product. Each animal model Models for Adipose Tissue Engineering. “Tissue
should be evaluated for its similarity with the human. Engineering. Part B, Reviews”. 2008; 14(2):
Due to unique sensitivities certain animal models may 167- 178.
not be applicable for certain biomaterials. [13][14] 9. Gomes PS, Fernandes MH. Rodent models in bone-
related research: the relevance of calvarial defects in
Animal research benefits not only humans, but also the the assessment of bone regeneration
animals. For example, animals, such as dogs and cats are strategies. 2011; 45: 14-24.

www.ejpmr.com 37
 Pehlivanović et al. European Journal of Pharmaceutical and Medical Research

10. Kerbel RS. What is the optimal rodent model for

anti-tumor drug testing? Cancer Metastasis Rev.
1999; 17: 301–4.
11. Gawrylewski A. The Trouble with Animal Models.
The Scientist, 2007.
12. Foster JR. A review of animal models of
nonneoplastic pancreatic diseases. Toxicol Pathol,
2014; 42: 243–259.
13. Syrng, G. Overview: FDA Regulation of Medical
Devices’, (2003), Available (12.05.2019.):
http://www.qrasupport.com/FDA_MED_DEVICE.h
tml
14. McCarthy TJ. Animal Models in Medical Device
Development and Qualification, Reference paper,
1997; 10: 2.
15. Wood C. Is Animal Testing about to become Ob-
solete? In: Casey Research; 2011.

www.ejpmr.com 38

View publication stats