CONTENTS

™ Introduction –
™ Definition
™ History
™ Need for animal models
™ Categories of animal models
™ Classification
™ Model selection
™ Species selection
™ Animal models used in periodontal research
™ Advantages in periodontal research
™ Limitations in periodontal studies
™ Controversies
™ The 3R Principle
™ Arrive guidelines
™ Criteria for humane death
™ Conclusion
™ References
 INTRODUCTION

–
™ In the 1920s, “experimental epidemiology” meant the study of
epidemics among colonies of experimental animals such as rats and
mice.

™ In modern usage, experimental epidemiology is often equated with

randomized controlled trials.
 –
The aims of experimental studies may be stated as follows :

™ a) to provide “scientific proof” of etiological (or risk) factors which may

permit the modification or control of those diseases

™ b) to provide a method of measuring the effectiveness and efficiency of

health services for the prevention, control and treatment of disease and to
improve the health of the community.
1.In Vitro study-Lab specimens. –
2.In Vivo study -Animal models
-Human beings
™ Throughout history animals have played an important role in men’s quest
for knowledge about himself and the environment.

™ Animal studies have contributed to our knowledge of anatomy, physiology,

pathology, microbiology, immunology, genetics, chemotherapy and so
many others.
 DEFINITION

–
™ Weggler in 1983 defined an animal model as a living organism with an
inherited, naturally acquired, or induced pathological process that in one or
more respects closely resembles the same phenomenon in men.

™ The institute of laboratory animal resources(ILAR) of the National Academy

of Sciences adopted and modified Weggler’s definition as follows:

An animal model is a living organism in which normative biology or behaviour

can be studied, or in which a spontaneous or induced pathological process can
be investigated, and in which the phenomenon in one or more respects
resembles the same phenomenon in humans or other species of animal.
 History:
–
™ Earliest reference.. Greeks (2nd /4th centuries BC)

™ Galen (2nd century Rome)..father of vivisection.

™ Insulin..from dogs (1922), revolutionized the treatment of diabetes.

™ 1957, Laika..

™ Dolly …1996..cloned adult cell..

™ Thalidomide tragedy.. toxicology studies

 Major advances in basic research that
depended on animal experiments
–
1600's - Function of the lungs, Measurement of blood pressure.

1800's – Vaccination, Understanding of infectious diseases

1900's - Antibodies, hormones

1930's - Mechanism of nerve impulses, tumor viruses.

1940's - Embryonic development

 Major advances in basic research that
depended on animal experiments
–
1960's - Monoclonal antibodies, liver functions

1970's - Transplantation antigens, brain functions, Discovery of prostaglandins

1980's - Development of transgenic animals

1990's - Understanding auto-immune disorders, In vitro fertilization, cloning

 NEED FOR THE ANIMAL MODELS

–
™ For ethical reasons, initiation and progression of periodontal disease as
well as certain types of periodontal treatment cannot be studied in
humans. Animal data can provide us with models of biologic trends
before proceeding to human application.
™ Inability to examine initiation and progression of periodontal diseases has
led to a great interest in the use of animal models in periodontal
research. Human longitudinal studies of periodontal disease pose many
problems such as determining the level of disease activity, individuals at
risk, and susceptibility of disease progression.
 –
™ Periodontal diseases can only be studied retrospectively in man, since reliable
clinical markers for ongoing tissue destruction (disease activity) are not
available. Therefore, an animal model in which selected microbiological and
immunological parameters can be studied prospectively is desirable.

™ Animal models have been used to evaluate various periodontal treatment

modalities like regenerative procedures like bone grafts and GTR, and
implant surgical procedures to study their safety and efficacy
 –
™ Though, there are computer models and cell cultures, as well as other adjunct
research methods, these methods are used to screen and determine the toxic
potential of a substance in the early stages of investigation. The final test,
however, has to be done in a whole, living system. Even the most sophisticated
technology cannot mimic the complicated interactions among cells, tissues and
organs that occur in humans and animals.

™ It is important to be able to test how a new drug or procedure will affect a

whole biological system before using it on humans. This is critical for scientific

as well as ethical reasons.

 CATEGORIES OF ANIMAL MODELS

–
™ INDUCED / EXPERIMENTAL MODELS
™ SPONTANEOUS / NATURAL MODELS
™ NEGATIVE / NON REACTIVE MODELS
™ ORPHAN MODELS
(Davidson et al 1987)
 CLASSIFICATION
(Page &Schroeder 1982)
–
I. Small rodents
E. g: Mice, Rats, Hamsters, Minks.

II. Larger animals

E. g: Dogs and sheep.

III. Non-Human primates

E. g: Baboon, Macaca, Chimpanzee and Gorilla

IV. Others
E. g: Apes, Cats, Horses, Guinea pigs, Mongooses, Wolves, Foxes,
Rabbits, Ferret etc.
 CRITERIA FOR SELECTION OF ANIMAL
MODELS
–
™ 1) appropriateness as an analog,
™ 2) transferability of information,
™ 3) genetic uniformity of organisms, where applicable,
™ 4) background knowledge of biological properties,
™ 5) cost and availability,
™ 6) generalizability of the results,
™ 7) ease of and adaptability to experimental manipulation,
™ 8) ecological consequences, and
™ 9) ethical implications
 CONSIDERATIONS FOR SPECIES
SELECTION:
–
™ Availability of laboratory facilities
™ Presence of a breeding colony
™ Cost
™ Ease of handling
™ Ease of housing
™ Relatedness to humans
™ Limitations imposed by the size of oral structures
™ Availability of appropriately sized periodontal instrument
 CONTROVERSIES

–
™ The use of animals for research and testing purposes has decreased substantially
during the last two decades but is now increasing again, mainly because of the
increased use of transgenic animal models.
™ Presently, 10-12 millions of vertebrate animals are used per year within EU
Member States.
™ Scientists who are using animals in research are frequently criticized by animal
protection groups and blamed that they do not respect the integrity of an animal's
life.

™ A study of 20 reviews of animal tests’ accuracy found that only two concluded
that the animal tests were consistent with the human findings or had contributed
significantly to developing new treatments.
™ The animal activists do not appreciate the use of animals in biological studies.
They are equating cruelty to animals committed by animal experiments
conducted for scientific investigations.
 THE “3 Rs” OF ANIMAL RESEARCH

–
™ REPLACEMENT
™ REDUCTION
™ REFINEMENT
(RUSSEL AND BURCH,1959)
ARRIVE GUIDELINES
–
–
–
–
 CRITERIA FOR A HUMANE DEATH

–
™ Death without signs of panic, pain or distress.
™ Minimum time to loss of consciousness.
™ Safety for personnel involved
™ Minimal undesirable physiological and psychological effect on animal
™ Minimal or no emotional effects on the observer and the operator
™ A location remote from animal rooms
 CONCLUSION
–
™ No genuine analogue of the various forms of human periodontitis
exists in animals.
™ A gold standard animal model in periodontology does not exist since
every application requires a model that fills specific needs.
™ Experimental models for periodontal diseases are essential for
understanding the origin and evolution of the pathology in humans.
™ The use of animal models in periodontal research is a necessary step
prior to entering into clinical trials with new biomaterials and
treatments.
™ The anatomy, physiology and pathogenicity of experimental models
should relate as much as possible to those of patients in order to
demonstrate the safety and efficacy of new biomaterials or treatments
in periodontal regeneration.
 REFERENCES
–
™ Amit Bhardwaj, Shalu V. Bhardwaj Contribution of Animal Models in
Periodontal Research IJAVMS, Vol. 6, Issue 3, 2012: 150-157
™ Xavier Struillou, Hervé Boutigny, Assem Soueidan, and Pierre
Layrolle,E xperimental Animal Models in Periodontology: A Review
The Open Dentistry Journal, 2010, 4, 37-47
™ Carlos Albuquerque, Francisco Morinha, João Requicha,Teresa
Martins, Isabel Dias Canine periodontitis: The dog as an important
model for periodontal studiesique .
™ Guedes-Pinto , Estela Bastos, Carlos Viegas The Veterinary Journal
191 (2012) 299–305
 –
™ Ashwini Ashok Apine and Shiva Prasad BM. Current Status of Animal
Experimentation in the Study of Periodontal Diseases and Therapeutics.
Research and Reviews: Journal of Dental Sciences

™ George Hajishengallisa, Richard J Lamontb & Dana T Graves The enduring

importance of animal models in understanding periodontal disease

™ The ARRIVE guidelines Animal Research: Reporting In Vivo Experiments

Carol Kilkenny, William J Browne, Innes C Cuthill, Michael Emerson4 and
Douglas G Altman

™ Helieh S. Oz and David A. Puleo Animal Models for Periodontal Disease

™ Amit Arvind Agrawal Considerations For Use Of Experimental Animals In

Biomedical And Periodontal Research