F O U R T H E D I T I O N BIOLOGICAL PERFORMANCE of MATERIALS Fundamentals of Biocompatibility F O U R T H E D I T I O N BIOLOGICAL PERFORMANCE of MATERIALS Fundamentals of Biocompatibility Jonathan Black Boca Raton London New York A CRC title, part of the Taylor & Francis imprint, a member of the Taylor & Francis Group, the academic division of T&F Informa plc. Copyright Jonathan Black. CRC Press Taylor & Francis Group 6000 Broken Sound Parkway NW, Suite 300 Boca Raton, FL 33487-2742 © 2006 by Taylor & Francis Group, LLC CRC Press is an imprint of Taylor & Francis Group, an Informa business No claim to original U.S. Government works Version Date: 20131106 International Standard Book Number-13: 978-1-4200-5784-3 (eBook - PDF) This book contains information obtained from authentic and highly regarded sources. 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For permission to photocopy or use material electronically from this work, please access www.copyright. com (http://www.copyright.com/) or contact the Copyright Clearance Center, Inc. (CCC), 222 Rosewood Drive, Danvers, MA 01923, 978-750-8400. CCC is a not-for-profit organization that provides licenses and registration for a variety of users. For organizations that have been granted a photocopy license by the CCC, a separate system of payment has been arranged. Trademark Notice: Product or corporate names may be trademarks or registered trademarks, and are used only for identification and explanation without intent to infringe. Visit the Taylor & Francis Web site at http://www.taylorandfrancis.com and the CRC Press Web site at http://www.crcpress.com Preface Biocompatibility of materials increasingly occupies the consciousness of engineers dealing with medical and biological problems. The engineer has long been accustomed to dealing with materials, limits on design. These limits, such as yield stress, endurance limit, and rupture life, are reflected in design margins tailored to the criticality of the specific application. In situ- ations involving biological interactions as a portion of the design problem, the additional materials limit of biocompatibility must be considered. Failure of compatibility (that is, incompatibility) is proving to be the ulti- mate limit to the engineering solution of many biomedical problems. As a result, it is necessary to incorporate a thorough grounding in the aspects of biocompatibility — or, as I prefer to term it more generally, biological per- formance of materials — into the training of bioengineers. When this book was first conceived, in the early 1970s, no suitable text- books dealing with broad aspects of biomedical materials or, as the field rapidly came to be called, biomaterials, were available. Today, as this field has matured into biomaterials science and engineering (BSE), many edited collections and topical monographs are available for students and workers at many different levels. However, none seems to suit the neophyte: the former are invariably written by a panel of experts and thus tend to be uneven in attempting to be comprehensive and the latter are the work of a single investigator or research group focusing on relatively narrow and parochial interests. Both of these types of books have a place and many are extremely valuable to the advanced worker, but they all fail to meet the needs of the student or the professional without a background in the field. Thus, it appears that the current work is still needed; it focuses primarily on principles of biological performance at a relatively fundamental level: interactions between living and nonliving materials whose consideration sets BSE apart as a distinct field of investigation and knowledge. Biological Performance of Materials: Fundamentals of Biocompatibility was orig- inally intended for use as an undergraduate text for a one-term, jun- ior–senior-level bioengineering course on biological performance. I and others have used it in this role. However, with the assignment of selected articles as reading and study sources, it has also proven useful as the central text in undergraduate survey courses on biomaterials and on artificial organs. With additional reading material from the scientific and clinical literature and from materials science texts, it has also been used as the focus of a first-year graduate course in biomaterials for students with engineering (but not biological or medical) backgrounds and, conversely, as a supple- mentary text for courses on implants for nursing students with little or no engineering training. Finally, engineers working in medical device develop- ment and evaluation in industrial as well as governmental settings have found it a useful reference book. The scarcity of reference to actual materials and specific applications has apparently made this diversity of use possible; this revision attempts to maintain the versatility of the work. Primary train- ing in materials science and biology is useful, but not totally essential, because this book is intended for use in conjunction with undergraduate texts in materials science and biology, as needed, so as to accommodate variations in individual degrees of preparation. We begin with an examination of the concept of “biocompatibility” and arguments for the broader concept of biological performance. Two major sections are devoted to the effect of biological systems on materials (“bio- degradation” = material response) and of materials on biological systems (“biocompatibility” = host response), respectively. Selected additional read- ings are provided at the end of each chapter. The reader will note an emphasis on methods for determination of biolog- ical performance, throughout and especially in Chapter 17 and Chapter 18. This reflects the centrality of material and host response in the clinical per- formance of medical devices and surgical implants as well as the continued need to select new and modified materials for specific applications. These questions become even more challenging and complex as increasing num- bers of viable and nonviable untraditional materials come under consider- ation for clinical use. The practicing engineer will find this book a useful source of references, test methods, and approaches to the problem of estab- lishing biological performance of materials. Generic materials properties are tabulated in Interpart 1; Interpart 2 is an example of diagnostic approaches to detection of clinical issues associated with biomaterials in animal models and in patients. The final four chapters deal with design, qualification, stan- dardization, and regulation of implant materials and will be of special assis- tance to the professional. In response to comments on earlier editions, an extensive glossary is also included. Due to the fundamental nature of this examination, I have elected in this revision to retain many earlier examples and studies, providing updated material and more current references only when needed. The reader is advised to make use of the online resources of the National Library of Medicine (PubMed*) to provide additional, more recent, and more special- ized information. I wish to thank the many undergraduate and graduate students and col- leagues whose ideas, questions, and discussions have contributed signifi- cantly to the scope and content of this work. Special thanks are due to G.K. Smith and J.L. Woodman for their seminal contributions to Chapter 14 and Chapter 15. An appeal for corrections and suggestions was issued to readers of two listserves (BIOMAT-L and BIOMCH-L) and considerable useful feed- back was received. * http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed. In the preface to the second edition (1992), I suggested that inappropriate host response to implants and premature device failure secondary to mate- rials degradation continue to impose unwanted limits on engineering solu- tions to biological and medical problems. This is still the case today. It can only be hoped that ideas and information contained in this revised work will contribute to the further improvement of biomaterials in their applica- tion to the alleviation of human disability, disorder, and disease. Jonathan Black Abstract Biological Performance of Materials: Fundamentals of Biocompatibility presents an organized approach to examining and understanding the interactions between materials used in medical devices and implants and living organ- isms. After an introductory section addressing definitions and aspects of biological environments, the work is divided into three principal sections. These deal with material response to biological systems, host response to biomaterials, and test methods for determining biological response in vitro as well as in animal models and clinical settings. Interparts provide summa- ries of physical properties of commonly used metallic, polymeric, and ceramic biomaterials as well as a guide to understanding clinical perfor- mance of implanted biomaterials. In addition to numerous references to the literature, each chapter includes an additional bibliography; an extensive glossary completes the work. Now in its fourth edition, this work draws on Black’s more than 35 years experience as a teacher, researcher, and consultant in biomaterials science and engineering.