BIOMATERIALS SCIENCE - Elsevier

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BIOMATERIALSSCIENCE

[01:53 29/4/03 RATNER-FM.tex]RATNER: Biomaterials SciencePage: ii [01:53 29/4/03 RATNER-FM.tex]RATNER: Biomaterials SciencePage: iii

BIOMATERIALSSCIENCE

An Introduction to

Materials in Medicine

2nd Edition

Edited by

Buddy D. Ratner, Ph.D.

Professor, Bioengineering and Chemical Engineering Director of University of Washington Engineered Biomaterials (UWEB), an

NSF Engineering Research Center

University of Washington, Seattle, WA USA

Allan S. Hoffman, ScD.

Professor of Bioengineering and Chemical Engineering

UWEB Investigator

University of Washington, Seattle, WA USA

Frederick J. Schoen, M.D., Ph.D.

Professor of Pathology and Health Sciences and Technology (HST)

Harvard Medical School

Executive Vice Chairman, Department of Pathology

Brigham and Womens Hospital

Boston, MA USA

Jack E. Lemons, Ph.D.

Professor and Director of Biomaterials Laboratory Surgical Research Departments of Prosthodontics and Biomaterials, Orthopaedic Surgery/Surgery and Biomedical Engineering, Schools of Dentistry, Medicine and Engineering

University of Alabama at Birmingham, AL USA

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Elsevier Academic Press

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Buddy D. Ratner ... [et al.].... 2nd ed.

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Includes bibliographical references and index.

ISBN 0-12-582463-7 (hardcover : alk. paper)

1. Biomedical materials.

[DNLM: 1. Biocompatible Materials. QT 37 B6145 1996] I. Ratner, B. D. (Buddy D.), 1947-

R857.M3B5735 2004

610
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2003027823

British Library Cataloguing in Publication Data

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[01:53 29/4/03 RATNER-FM.tex]RATNER: Biomaterials SciencePage: v

CONTENTS

Contributors ix

Preface xi

Biomaterials Science: A Multidisciplinary

Endeavor1

BUDDY D. RATNER, ALLAN S. HOFFMAN, FREDERICK J. SCHOEN,

AND JACK LEMONS

A History of Biomaterials10

BUDDY D. RATNER

PARTI

MATERIALS SCIENCE AND

ENGINEERING

CHAPTER 1 Properties of Materials

1.1 Introduction23

JACK E. LEMONS

1.2 Bulk Properties of Materials23

FRANCIS W. COOKE

1.3 Finite Element Analysis32

IVAN VESELY AND EVELYN OWEN CAREW

1.4 Surface Properties and Surface

Characterization of Materials40

BUDDY D. RATNER

1.5 Role of Water in Biomaterials59

ERWIN A. VOGLER

CHAPTER 2 Classes of Materials Used in

Medicine

2.1 Introduction67

ALLAN S. HOFFMAN

2.2 Polymers67

STUART L. COOPER, SUSAN A. VISSER,

ROBERT W. HERGENROTHER, AND NINA M. K. LAMBA

2.3 Silicone Biomaterials: History

and Chemistry80

ANDRÉ COLAS AND JIM CURTIS

2.4 Medical Fibers and Biotextiles86

STEVEN WEINBERG AND MARTIN W. KING

2.5 Hydrogels100

NICHOLAS A. PEPPAS

2.6 Applications of Smart PolymersŽ as

Biomaterials107

ALLAN S. HOFFMAN

2.7 Bioresorbable and Bioerodible Materials115

JOACHIM KOHN, SASCHA ABRAMSON, AND ROBERT LANGER

2.8 Natural Materials127

IOANNIS V. YANNAS

2.9 Metals137

JOHN B. BRUNSKI

2.10 Ceramics, Glasses, and Glass-Ceramics153

LARRY L. HENCH AND SERENA BEST

2.11 Pyrolytic Carbon for Long-Term Medical

Implants170

ROBERT B. MORE, AXEL D. HAUBOLD, AND JACK C. BOKROS

2.12 Composites181

CLAUDIO MIGLIARESI AND HAROLD ALEXANDER

2.13 Nonfouling Surfaces197

BUDDY D. RATNER AND ALLAN S. HOFFMAN

v [01:53 29/4/03 RATNER-FM.tex]RATNER: Biomaterials SciencePage: vi viCONTENTS

2.14 Physicochemical Surface Modi“cation

of Materials Used in Medicine201

BUDDY D. RATNER AND ALLAN S. HOFFMAN

2.15 Textured and Porous Materials218

JOHN A. JANSEN AND ANDREAS F. VON RECUM

2.16 Surface-Immobilized Biomolecules225

ALLAN S. HOFFMAN AND JEFFREY A. HUBBELL

PARTII

BIOLOGY, BIOCHEMISTRY,

AND MEDICINE

CHAPTER 3 Some Background Concepts

3.1 Background Concepts237

BUDDY D. RATNER

3.2 The Role of Adsorbed Proteins in Tissue

Response to Biomaterials237

THOMAS A. HORBETT

3.3 Cells and Cell Injury246

RICHARD N. MITCHELL AND FREDERICK J. SCHOEN

3.4 Tissues, the Extracellular Matrix, and

Cell...Biomaterial Interactions260

FREDERICK J. SCHOEN AND RICHARD N. MITCHELL

3.5 Mechanical Forces on Cells282

LARRY V. MCINTIRE, SUZANNE G. ESKIN, AND ANDREW YEE

CHAPTER 4 Host Reactions to Biomaterials

and Their Evaluation

4.1 Introduction293

FREDERICK J. SCHOEN

4.2 In"ammation, Wound Healing, and the

Foreign Body Response296

JAMES M. ANDERSON

4.3 Innate and Adaptive Immunity: The Immune

Response to Foreign Materials304

RICHARD N. MITCHELL

4.4 The Complement System318

RICHARD J. JOHNSON

4.5 Systemic Toxicity and Hypersensitivity328

ARNE HENSTEN-PETTERSEN AND NILS JACOBSEN

4.6 Blood Coagulation and Blood...Materials

Interactions332

STEPHEN R. HANSON

4.7 Tumorigenesis and Biomaterials338

FREDERICK J. SCHOEN

4.8 Bio“lms, Biomaterials, and Device-Related

Infections345

BILL COSTERTON, GUY COOK, MARK SHIRTLIFF,

PAUL STOODLEY, AND MARK PASMORE

CHAPTER 5 Biological Testing of Biomaterials

5.1 Introduction to Testing Biomaterials355

BUDDY D. RATNER

5.2In VitroAssessment of Tissue

Compatibility356

SHARON J. NORTHUP

5.3In VivoAssessment of Tissue

Compatibility360

JAMES M. ANDERSON AND FREDERICK J. SCHOEN

5.4 Evaluation of Blood-Materials Interactions367

STEPHEN R. HANSON AND BUDDY D. RATNER

5.5 Large Animal Models in Cardiac and

Vascular Biomaterials Research

and Testing379 RICHARD W. BIANCO, JOHN F. GREHAN, BRIAN C. GRUBBS,

JOHN P. MRACHEK, ERIK L. SCHROEDER,

CLARK W. SCHUMACHER, CHARLES A. SVENDSEN,

AND MATT LAHTI

5.6 Microscopy for Biomaterials Science396

KIP D. HAUCH

CHAPTER 6 Degradation of Materials in the

Biological Environment

6.1 Introduction: Degradation of Materials in the

Biological Environment411

BUDDY D. RATNER

6.2 Chemical and Biochemical Degradation of

Polymers411

ARTHUR J. COURY

6.3 Degradative Effects of the Biological

Environment on Metals and Ceramics430

DAVID F. WILLIAMS AND RACHEL L. WILLIAMS

6.4 Pathological Calci“cation of Biomaterials439

FREDERICK J. SCHOEN AND ROBERT J. LEVY

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CONTENTSvii

CHAPTER 7 Application of Materials in Medicine,

Biology, and Arti“cial Organs

7.1 Introduction455

JACK E. LEMONS AND FREDERICK J. SCHOEN

7.2 Nonthrombogenic Treatments and Strategies456

MICHAEL V. SEFTON AND CYNTHIA H. GEMMELL

7.3 Cardiovascular Medical Devices470

ROBERT F. PADERA, JR., AND FREDERICK J. SCHOEN

7.4 Implantable Cardiac Assist Devices494

WILLIAM R. WAGNER, HARVEY S. BOROVETZ,

AND BARTLEY P. GRIFFITH

7.5 Arti“cial Red Blood Cell Substitutes507

THOMAS MING SWI CHANG

7.6 Extracorporeal Arti“cial Organs514

PAUL S. MALCHESKY

7.7 Orthopedic Applications526

NADIM JAMES HALLAB, JOSHUA J. JACOBS,

AND J. LAWRENCE KATZ

7.8 Dental Implantation555

A. NORMAN CRANIN AND JACK E. LEMONS

7.9 Adhesives and Sealants572

DENNIS C. SMITH

7.10 Ophthalmological Applications583

MIGUEL F. REFOJO

7.11 Intraocular Lens Implants: A Scienti“c

Perspective591

ANIL S. PATEL

7.12 Burn Dressings and Skin Substitutes602

JEFFREY R. MORGAN, ROBERT L. SHERIDAN,

RONALD G. TOMPKINS, MARTIN L. YARMUSH,

AND JOHN F. BURKE

7.13 Sutures614

MARK S. ROBY AND JACK KENNEDY

7.14 Drug Delivery Systems628

JORGE HELLER AND ALLAN S. HOFFMAN

7.15 Bioelectrodes648

RAMAKRISHNA VENUGOPALAN AND RAY IDEKER

7.16 Cochlear Prostheses657

FRANCIS A. SPELMAN

7.17 Biomedical Sensors and Biosensors669

PAUL YAGER

7.18 Diagnostics and Biomaterials684

PETER J. TARCHA AND THOMAS E. ROHR

7.19 Medical Applications of Silicones697

JIM CURTIS AND ANDRÉ COLAS

CHAPTER 8 Tissue Engineering

8.1 Introduction709

FREDERICK J. SCHOEN

8.2 Overview of Tissue Engineering712

SIMON P. HOERSTRUP AND JOSEPH P. VACANTI

8.3 Immunoisolation728

MICHAEL J. LYSAGHT AND DAVID REIN

8.4 Synthetic Bioresorbable Polymer Scaffolds735

ANTONIOS G. MIKOS, LICHUN LU, JOHNNA S. TEMENOFF,

AND JOERG K. TESSMAR

PARTIII

PRACTICAL ASPECTS OF

BIOMATERIALS

CHAPTER 9 Implants, Devices, and Biomaterials:

Issues Unique to This Field

9.1 Introduction753

FREDERICK J. SCHOEN

9.2 Sterilization of Implants and Devices755

JOHN B. KOWALSKI AND ROBERT F. MORRISSEY

9.3 Implant and Device Failure760

FREDERICK J. SCHOEN AND ALLAN S. HOFFMAN

9.4 Correlation, Surfaces and Biomaterials

Science765

BUDDY D. RATNER

9.5 Implant Retrieval and Evaluation771

JAMES M. ANDERSON, FREDERICK J. SCHOEN,

STANLEY A. BROWN, AND KATHARINE MERRITT

CHAPTER 10 New Products and Standards

10.1 Introduction783

JACK E. LEMONS

10.2 Voluntary Consensus Standards783

JACK E. LEMONS

10.3 Development and Regulation of Medical

Products Using Biomaterials788

ELAINE DUNCAN

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10.4 Ethical Issues in the Development of

New Biomaterials793

SUBRATA SAHA AND PAMELA SAHA

10.5 Legal Aspects of Biomaterials797

JAY P. MAYESH AND MARY F. SCRANTON

CHAPTER 11 Perspectives and Possibilities in

Biomaterials Science

805

BUDDY D. RATNER, FREDERICK J. SCHOEN,

JACK E. LEMONS, AND ALLAN S. HOFFMAN

APPENDIX A Properties of Biological Fluids813

STEVEN M. SLACK

APPENDIX B Properties of Soft Materials819

M. CRISTINA L. MARTINS

APPENDIX C Chemical Compositions of Metals

Used for Implants

823

JOHN B. BRUNSKI

APPENDIX D The Biomaterials Literature825

Index831

[01:15 1/4/03 RATNER-FM.tex]RATNER: Biomaterials SciencePage: ix

EDITORS ANDLEADCONTRIBUTORS

Numbers in parentheses indicate the pages on which the authors" contributions begin. Harold Alexander(180) Orthogen Corporation, Springfield,

NJ 07081

James M. Anderson(296, 360, 771) Institute of Pathology, Case Western Reserve University, Cleveland, OH 44106 Richard W. Bianco(379) Division of Experimental Surgery, DepartmentofSurgery,UniversityofMinnesota,Minneapolis,

MN 55455

John B. Brunski(137, 823) Department of Biomedical Engi- neering, Rensselaer Polytechnic Institute, Troy, NY 12180 ThomasM.S.Chang(507)ArtificialCellsandOrganResearch Centre, McGill University, Montreal, Quebec H3G 1Y6,

Canada

AndérColas(80, 697)DowCorningLifeSciences, B-7180Sen- effe, Belgium FrancisW.Cooke(23)OrthopedicResearchInstitute, Wichita,

KS 67214

Stuart L. Cooper(67) Ohio State University, Department of

Chemical Engineering, Raleigh, Columbia, OH 43210

Joachim Kohn(115) Department of Chemistry, Rutgers, The State University of New Jersey, Piscataway, NJ 08854 Bill Costerton(345) Center for Biofilm Engineering, College of Engineering, Montana State University, Bozeman, MT 59717
Arthur J. Coury(411) Biomaterials Research, Genzyme Cor- poration, Cambridge, MA 02139 A. Norman Cranin(555) Brookdale University Hospital and Medical Center, The Dental Implant Group, Brooklyn,

NY 11212

Jim Curtis(80, 697) Life Sciences Industry, Medical Device

Operations,DowCorningCorporation,Midland,MI48686

Elaine Duncan(788) Paladin Medical, Stillwater, MN 55082 NadimJamesHallab(526)DepartmentofOrthopedicSurgery,

Rush Medical College, Chicago, IL 60612

StephenR.Hanson(328, 367)DepartmentofBiomedicalEngi- neering, Oregon Health Sciences University, Beaverton, OR

97006Kip D. Hauch(396) Department of Chemical Engineering,

University of Washington, Seattle, WA 98195

Jorge Heller(628) A.P. Pharma, Department of Research,

Redwood City, CA 94063

Larry L. Hench(153) Department of Materials, Imperial College of Science, Technology and Medicine, University of

London, London SW7 2BP, United Kingdom

Arne Hensten-Pettersen(328) Scandinavian Institute of Dental

Materials (NIOM), Haslum, Norway

Simon P. Hoerstrup(712) Clinic for Cardiovascular Surgery,

University Hospital, CH8091, Zurich, Switzerland

Allan S. Hoffman(1, 67, 109, 197, 201, 225, 628, 760, 805) Department of Bioengineering, University of Washington,

Seattle, WA 98195

Thomas A. Horbett(234) Center for Bioengineering and

Department of Chemical Engineering, University of

Washington, Seattle, WA 98195

John A. Jansen(218) Department of Biomaterials, Dental School, University of Nijmegen, 6500 HB, Nijmegen, The

Netherlands

Richard J. Johnson(318) Exploratory Research, Baxter

Healthcare Coporation, Round Lake, IL 60073

John B. Kowalski(754) Sterilization Science & Technology,

Johnson & Johnson, New Brunswick, NJ 08906

Jack E. Lemons(1, 23, 455, 783, 805) Department of Bio- materials and Surgery, School of Dentistry and Medicine,

University of Alabama, Birmingham, AL 35294

Michael J. Lysaght(728) Center for Biomedical Engineering,

Brown University, Providence, RI 02912

Paul S. Malchesky(514) International Center for Artificial

Organs and Transplantation, Painesville, OH 44077

M. Cristina L. Martins(819) INEB-Instituto de Engenharia Biomédica, Laboratório de Biomateriais, Universidade do

Porto, 4150-180 Porto, Portugal

Jay P. Mayesh(797) Kaye, Scholer, LLP, New York, NY 10022
Larry V. McIntire(282) Department of Bioengineering, Institute of Bioscience & Bioengineering, Rice University,

Houston, TX 77005

ix [01:15 1/4/03 RATNER-FM.tex]RATNER: Biomaterials SciencePage: x xEDITORS AND LEAD CONTRIBUTORS Claudio Migliaresi(181) Department of Materials Engineer- ingandIndustrialTechnologies, UniversityofTrento, 38050

Trento, Italy

Antonios G. Mikos(735) Department of Bioengineering,

Rice University, Houston, TX 77251

RichardN.Mitchell(246, 260, 304)DepartmentofPathology,

Brigham and Women"s Hospital, Boston, MA 02115

Robert B. More(170) Medical Carbon Research Institute,

Austin, TX 78754

Jeffrey R. Morgan(602) Department of Molecular Pharma- cology, Physiology, and Biotechnology, Biomedical Center,

Providence, RI 02912

Sharon J. Northup(356) Northup RTS, Highland Park, IL 60035
Robert F. Padera, Jr.(470) Department of Pathology, Brigham and Women"s Hospital, Boston, MA 02115 Anil S. Patel(591) Alcon Labs Retiree, Seattle, WA 98115 Nicholas A. Peppas(100) Department of Chemical Engi- neering, The University of Texas at Austin, Austin, TX 78712
Buddy D. Ratner(1, 10, 40, 197, 201, 237, 355, 367, 411,

803) University of Washington Engineered Biomaterials,

University of Washington, Seattle, WA 98195

Miguel F. Refojo(583) Department of Opthalmology, The Schepens Eye Research Institute, Harvard Medical School,

Boston, MA 02114

Mark S. Roby(614) United States Surgical, North Haven,

CT 06473

Subrata Saha(793) Biomedical Engineering Science Program,

Alfred University, Alfred, NY 14802

Frederick J. Schoen(1, 246, 260, 293, 338, 360, 439, 455,

470, 709, 753, 760, 771, 805) Department of Pathology,Brigham and Women"s Hospital, Harvard Medical School,Boston, MA 02115

Michael V. Sefton(456) Institute of Biomaterials and Biomed- ical, UniversityofToronto, Toronto, ONM533G9, Canada Steven M. Slack(813) Department of Biomedical Engineering,

University of Memphis, Memphis, TN 38152

Dennis C. Smith(572) Centre for Biomaterials, University of

Toronto, Toronto, ON L9Y 3Y9, Canada

Francis A. Spelman(656)Advanced Cochlear Systems, Sno- qualmie, WA. Department of Bioengineering, University of

Washington, Seattle, WA 98195

Peter J. Tarcha(684) Abbott Laboratories, Department of

Advanced Drug Delivery, Abbott Park, IL 60064

Ramakrishna Venugopalan(648) Codman and Shurtleff,

A J&J Company, Raynham, MA 02767

Ivan Vesely(32) The Saban Research Institute of Children"s

Hospital, Los Angeles, Los Angeles, CA 90027

Erwin A. Vogler(59) Department of Materials Science and Engineering and Bioengineering, Materials Research Insti- tute, Penn State University, University Park, PA 16802 William R. Wagner(454) Presbyterian University Hospital,

University of Pittsburgh, Pittsburgh, PA 15219

Steven Weinberg(86) Biomedical Device Consultants and

Laboratories, Inc., Webster, TX 77598

David F. Williams(430) Department of Clinical Engineering, Royal Liverpool University Hospital, The University of Liv- erpool, Liverpool, L69 3BX, United Kingdom Paul Yager(669) Department of Bioengineering, University of

Washington, Seattle,WA 98195

Ioannis V. Yannas(127) Department of Mechanical Engineer- ing, Massachusetts Institute of Technology, Cambridge, MA 02139
[14:47 3/4/03 PREF.tex]RATNER: Biomaterials SciencePage: xi

PREFACE

The interest and excitement in the field of biomaterials has beenvalidatedbysalesofthefirsteditionofthistextbook:more than 10,000 copies sold. Also, the first edition has been widely adopted for classroom use throughout the world. The concept behind the first edition was that a balanced textbook on the subject of biomaterials science was needed. As with the first edition, the intended audience is multidisciplinary: students of medicine, dentistry, veterinary science, engineering, materials science, chemistry, physics, and biology (not an all-inclusive list) can find essential introductory material to permit them a reasonably knowledgeable immersion into the key professional issues in biomaterials science. Textbooks by single authors too strongly emphasize their own areas of expertise and ignore other important subjects. Articles from the literature are commonly used in the class- room setting, but these are difficult to weave into a cohe- sive curriculum. Handout materials from professors are often graphically unsophisticated, and again, slanted to the spe- cific interests of the individual. InBiomaterials Science: An Introduction to Materials in Medicine, 2nd edition, we the editors (whose 140+ person-year expertise spans materials science, pathology, and hard- and soft-tissue applications), endeavor to present a balanced perspective on an evolving discipline by integrating the experience of many leaders in the biomaterials field. Balanced presentation means appropri- ate representation of hard biomaterials and soft biomaterials; of orthopedic ideas, cardiovascular concepts, ophthalmologic ideas, and dental issues; a balance of fundamental biologi- cal concepts, materials science background, medical/clinical concerns, and government/societal issues; and coverage of bio- materials past, present, and future. In this way, we hope that the reader can visualize the scope of the field, absorb the unifying principles common to all materials in contact with biological systems, and gain a solid appreciation for the spe- cial significance of the wordbiomaterialas well as the rapid and exciting evolution and expansion of biomaterials science and its applications in medicine. More than 108 biomaterials professionals from academia, industry, and government have contributed to this work. Cer- tainly, such a distinguished group of authors provides the

neededbalanceandperspective.However,suchadiversegroupof authors also leads to unique complexities in a project of this

type. Do the various writing styles clash? Does the presentation of material, particularly controversial material, result in one chapter contradicting another? Even with so many authors, all subjectsrelevanttobiomaterialscannotbeaddressed-subjects should be included and which left out? How should such a project be refereed to ensure scientific quality, pedagogical effectiveness, and the balance we strive for? These are some of the issues the editors grappled with over theyearsfromconceptionofthesecondeditionin1998topub- lication in 2004. From this complex editorial process, a unique volume has evolved that the editors feel can make an ongo- ing contribution to the development of the biomaterials field. An educational tool has been synthesized here directing those new to biomaterials, be they engineers, physicians, materials scientists, or biochemists, on a path to appreciating the scope, complexity, basic principles, and importance of this enterprise. What"s new inBiomaterials Science: An Introduction to Materials in Medicine, 2nd edition? All chapters have been updated and rewritten, most extensively. A large number of new chapters have been added. The curricular organization for teaching the fundamental cell biology, molecular biology, tissue organization, and histology, key subjects that support the modern biomaterials research endeavor, has been restruc- tured. A new, three-chapter section on tissue engineering has been added. The total content and size of the book have been significantly increased. A Web site has been coupled to the book offering supplemental material including surgery movies and homework problems. The graphics design has been upgraded.Youhaveinyourhandsanewbookthatcanaddress biomaterials in the 21st century. Acknowledgments and thanks are in order. First, let us address the Society For Biomaterials that served as sponsor and inspiration for this book. The Society For Biomaterials is a model of "scientific cultural diversity" with engineers, physicians, scientists, veterinarians, industrialists, inventors, regulators, attorneys, educators, and ethicists all participating in an endeavor that is intellectually exciting, humanitarian, and profitable. As with the first edition, all royalties from this volume are being returned to the Society For Biomateri- als to further education and professional advancement relatedxi [14:47 3/4/03 PREF.tex]RATNER: Biomaterials SciencePage: xii xiiPREFACE tobiomaterials.ForfurtherinformationontheSocietyForBio- materials,visittheSFBWebsite(http://www.biomaterials.org/). Next,weofferaspecialthankstothosewhoenthusiastically investedtime,energy,experience,andintelligencetoauthorthe chaptersthatarethistextbook.Themanyscientists,physicians, and engineers who contributed their expertise and perspectives are clearly the backbone of this work and they deserve high praise"their efforts will strongly affect the education of the nextgenerationofbiomaterialsscientists.Also,somereviewers assisted the editors in carefully refereeing chapters. We thank Kip Hauch, Colleen Irvin, Gayle Winters, Tom Horbett, and

Steven Slack.

The support, encouragement, organizational skills, and experience of the staff, "rst at Academic Press and now at Elsevier Publishers, have led this second edition from vision to volume. Thank you, Elsevier, for this contribution to the "eld of biomaterials. Finally, a unique person at the University of Washington

has contributed to the assembly and production aspects ofthis work. We offer special thanks to Elizabeth Sharpe for

her superb editorial/organizational efforts. This volume, deep down,hasElizabethsintelligentandquality-orientedstampall over it. Clearly, she cares! The biomaterial "eld has always been ripe with opportuni- ties, stimulation, compassion, and intellectual ideas. As a "eld welooktothehorizonswherethenewideasfromscience,tech- nology, and medicine arise. We aim to improve the quality of life for millions through biomaterials-based, improved medical devices and tissue engineering. We editors hope the biomate- rials overview you now hold will stimulate you as much as it has us.

Buddy D. Ratner

Allan S. Hoffman

Jack E. Lemons

Frederick J. Schoen

May 2004