Animal Models In Orthopaedic Research

Edited by

Yuehuei H. An, M.D.
Richard J. Friedman, M.D.

CRC Press, Inc., Boca Raton, Florida, USA, 1999
Date of publication: September 1998, Cat#: 2115

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Preface

Research using animal models provides important knowledge of pathological conditions that can eventually lead to the development of more effective clinical treatment of diseases in both human and animals. This book covers most of the major animal models used in studies of biomaterials and orthopaedic disorders. It is to be used as a reference book and is primarily directed towards surgeons, investigators, research fellows, graduate students, or anyone working in the field of orthopaedic or biomaterial research. It is intended to serve as a basis for a literature search before embarking on a detailed research project. It is possible that other scientists or physicians in areas unrelated to orthopaedic or biomaterial research may also find this material useful as a source of reference, or as a tool to expedite their research.

This book is an outgrowth of the editors' own quest for information about animal research methodology in orthopaedic and biomaterial research and, more importantly, represents tremendous support from the orthopaedic and biomaterial research communities. The eleven chapters written by the editors are a combination of knowledge gained from personal experience and the research literature. The remaining twenty chapters are contributions from forty five well-known experts in their fields of interests from throughout the world.

The book has thirty one chapters and is divided into eight major parts. Part I is a general discussion about the care and use of laboratory animals and experimental designs in orthopaedic research. Part II describes the most commonly used evaluation methods in orthopedic animal research. Detailed descriptions of common animal models used in orthopaedic research are given in Parts III through VIII.

The book is designed to be concise as well as inclusive and more practical than theoretical. The text is simple and straightforward. Appropriate number of tables, diagrams, line figures, and photographs are used to make the contents more vivid. The appendices include a list of periodicals and publications related to orthopaedic research, laboratory animals, and procurement sources. Full bibliographies at the end of each chapter guide readers to more detailed information on the subject. A book of this length cannot possibly discuss every animal model that has ever been produced in orthopaedic research, but it is felt that the major models and their applications have been included.

Yuehuei H. An, M.D.
Richard J. Friedman, M.D.

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Foreword

Research is at the heart of progress in orthopaedic surgery as it is in all other fields of medicine. The products of research have changed the face of orthopaedics and have provided for millions of human beings the chance of enjoying active and productive lives. Research encompasses a broad range of activities, but it should always begin with a burning question that will lead to the development of one or more hypotheses and the need to test them experimentally. For that purpose, there are a number of methods available to the investigator. They include in-vitro experiments, the use of cadaveric material, computer models, physical models, and clinical databases.

Animal models are an integral part of the process and, as such, are frequently used in orthopaedic research. However, prior to their application there are some fundamental issues that must be addressed. Is the animal experiment truly necessary or can the questions be answered using other methods?

Experimental work requiring the use of living creatures can never be taken lightly. An enormous controversy surrounds us regarding the ethical issues involved. Thus, the use of animal models for subjects that are important to mankind can only be justified when there is no other viable alternative. Experiments in animals when justified and properly planned and executed have been essential in the acquisition of new knowledge.

Animal models have allowed us to understand the natural history of disease, to develop new and improved surgical techniques, and to predict the effect of a given treatment or surgical procedure. They have been critical in the development and in the evaluation of implants, one of the basic elements of modern orthopaedics. Animal models play a crucial role in biocompatibility evaluation which is the most fundamental basis of knowledge necessary in the biomaterials field. Tissue engineering and the use of new technologies based on molecular biology developments require animal experiments. And the list can goes on and on. In every aspect of orthopaedic research, the use of animal models constitute an essential step that leads to the eventual application of newly acquired information to the human patient.

This work addresses a very important subject and one that to my knowledge has not been covered in such a comprehensive manner in any other book or publication. There are a number of features that make this book unique in addition to the subject and the depth in which it has been addressed. The editors have played a very active role in the conception and in the execution of the project. Out of the 31 chapters that compose the book, 11 were written by the editors themselves. This is unusual and reflects on the one hand their expertise and knowledge of the subject and, on the other, the level of their commitment.

The book is divided into eight parts. The first two deal with principles to detailed methodology. The other six address the use of models for specific purposes. Given the nature of the musculoskeletal system, a broad picture needs to be considered. Bone, cartilage, joint replacement, ligaments and tendons, spinal conditions and microsurgical techniques are included with chapters that address in detail the use of animal models in most areas of related research.

I particularly enjoyed Part One of the book, including all its five chapters which by themselves represent in my judgment a major contribution. The ethical issues involved are presented in a very objective light, taking into account the concerns of the orthopaedic research community as well as those of animal rights advocates. This is a topic with which all investigators should be very familiar.

There is no research without appropriate experimental design. The young investigator will find important information to guide him from the conception of the basic ideas, to the development and execution of the experiment, and to the eventual publication of results in a scientific journal. My own perception is that it will be among our young trainees and investigators that this book will have its major impact. The seasoned researcher and the basic scientist will find this book very valuable as well, and an excellent source of reference given the breadth with which the subject has been approached. This book has a great deal to offer to everyone involved in orthopaedic research.

Jorge O. Galante, M.D.

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Table of Contents

Part I - General Considerations of Using Laboratory Animals
Chapter 1. Ethics and Regulations for the Care and Use of Laboratory Animals - Alison C. Smith, Richard T. Fosse, M. Michael Swindle

Chapter 2. Experimental Design, Evaluation Methods, Data Analysis, Publication, and Research Ethics - Yuehuei H. An, Todd D. Bell

Chapter 3. Animal Selections in Orthopaedic Research - Yuehuei H. An, Richard J. Friedman

Chapter 4. Surgical Facilities, Peri-operative Care, Anesthesia, and Surgical Techniques - Alison C. Smith, M. Michael Swindle

Chapter 5. Euthanasia and Necropsy - Sarah A. Bingel

Part II - Evaluation Methods in Orthopaedic Animal Research
Chapter 6. Methods of Evaluation in Orthopaedic Animal Research - Yuehuei H. An

Chapter 7. Histological Study in Orthopaedic Animal Research - Helen E. Gruber, Audrey A. Stasky

Chapter 8. Mechanical Properties and Testing Methods of Bone - Yuehuei H. An, Robert A. Draughn

Chapter 9. Mechanical Testing of Cartilage - Martine LaBerge

Chapter 10. Mechanical Testing of Ligament and Tendon - Savio L-Y. Woo, Theodore T. Manson, Tracy M. Vogrin

Part III - Animal Models of Bone Conditions
Chapter 11. Animal Models of Fracture or Osteotomy - Yuehuei H. An, Richard J. Friedman, Robert A. Draughn

Chapter 12. Animal Models for Testing Bioabsorbable Materials - Yuehuei H. An, Richard J. Friedman

Chapter 13. Animal Models of Bone Defect Repair - Yuehuei H. An, Richard J. Friedman

Chapter 14. Animal Models of Osteonecrosis - Kensaku Masuhara, Minoru Matui, Katsuya Nakata, Keiro Ono

Chapter 15. Animal Models of Osteopenia or Osteoporosis - Donald B. Kimmel, Erica L. Moran, Earl R. Bogoch

Part IV - Animal Models of Articular Cartilage and Joint Conditions
Chapter 16. Animal Models of Articular Cartilage Defect - Yuehuei H. An, Richard J. Friedman

Chapter 17. Animal Models of Meniscal Repair - Jan Klompmaker, René P.H. Veth

Chapter 18. Animal Models of Osteoarthritis - Theodore R. Oegema, Jr., Denise M. Visco

Chapter 19. Animal Models of Inflammatory Arthritis - Erica L. Moran, Earl R. Bogoch

Part V - Animal Models of Joint Replacement and Related Conditions
Chapter 20. Animal Models for Studying Soft Tissue Biocompatibility of Biomaterials - John A. Jansen

Chapter 21. Animal Models for Studying Bone Ingrowth and Joint Replacement - Dale R. Sumner, Thomas M. Turner, Robert M. Urban

Chapter 22. Animal Models for Investigations of Biomaterial Debris - Martin Lind, Yong Song, Stuart B. Goodman

Chapter 23. Animal Models of Prosthetic Infection - Yuehuei H. An, Richard J. Friedman

Part VI - Animal Models for the Study of Ligaments and Tendons
Chapter 24. Animal Models of Ligament Repair - Jason J. McDougall, Robert C. Bray

Chapter 25.Animal Models of Tendon Repair - Donald L. Pruitt

Chapter 26. Animal Models for Ligament and Tendon Fixation to Bone - Frank A. Young, Yuehuei H. An

Part VII - Animal Models of Spinal Conditions
Chapter 27. Animal Models of Spinal Instability and Spinal Fusion - Harvinder S. Sandhu, Linda E.A. Kanim, Federico Girardi, Frank P. Cammisa, Jr., Edgar D. Dawson

Chapter 28. Animal Models of Spinal Cord Compression - Shimpei Miyamoto, Kazuo Yonenobu, Keiro Ono

Chapter 29. Animal Models of Transplantation and Replacement of Vertebral Column and Intervertebral Disc - Hiromi Matsuzaki, Ken Wakabayashi

Chapter 30. Animal Models of Scoliosis - Noriaki Kawakami, Masao Deguchi, Tokumi Kanemura

Part VIII - Microsurgical Technique
Chapter 31. Use of Microsurgical Technique in Orthopaedic Animal Models - Yuehuei H. An

Appendix
1. Abbreviations
2. Journals and Publications Related to Orthopedic Research and Laboratory Animals
3. Major Sources of Laboratory Animals

Index

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