Biomaterials Science: An Introduction to Materials in Medicine

By Michael J. Yaszemski

The revised edition of the renowned and bestselling title is the most comprehensive single text on all aspects of biomaterials science from principles to applications. Biomaterials Science, fourth edition, provides a balanced, insightful approach to both the learning of the science and technology of biomaterials and acts as the key reference for practitioners who are involved in the applications of materials in medicine.This new edition incorporates key updates to reflect the latest relevant research in the field, particularly in the applications section, which includes the latest in topics such as nanotechnology, robotic implantation, and biomaterials utilized in cancer research detection and therapy. Other additions include regenerative engineering, 3D printing, personalized medicine and organs on a chip. Translation from the lab to commercial products is emphasized with new content dedicated to medical device development, global issues related to translation, and issues of quality assurance and reimbursement. In response to customer feedback, the new edition also features consolidation of redundant material to ensure clarity and focus. Biomaterials Science, 4th edition is an important update to the best-selling text, vital to the biomaterials’ community.

• The most comprehensive coverage of principles and applications of all classes of biomaterials
• Edited and contributed by the best-known figures in the biomaterials field today; fully endorsed and supported by the Society for Biomaterials
• Fully revised and updated to address issues of translation, nanotechnology, additive manufacturing, organs on chip, precision medicine and much more.
• Online chapter exercises available for most chapters

• Language: English
• Publisher: Academic Press
• Release date: May 23, 2020
• ISBN: 9780128161388

Book preview

Biomaterials Science

An Introduction to Materials in Medicine

Fourth Edition

Edited by

William R. Wagner

Distinguished Professor of Surgery, Bioengineering & Chemical Engineering, University of Pittsburgh, Director, McGowan Institute for Regenerative Medicine, Pittsburgh, PA, United States

Shelly E. Sakiyama-Elbert

Professor and Department Chair, Fletcher Stuckey Pratt Chair in Engineering, Department of Biomedical Engineering, The University of Texas at Austin, Austin, TX, United States

Guigen Zhang

Professor and F Joseph Halcomb III, M.D. Endowed Chair, Chair of the F. Joseph Halcomb III, M.D. Department of Biomedical Engineering, University of Kentucky, Lexington, KY, United States

Michael J. Yaszemski

Krehbiel Family Endowed Professor of Orthopedics and Biomedical Engineering, Mayo Clinic, Rochester, MN, United States

Table of Contents

Cover image

Title page

Materials Science and Engineering

Section 1.1. Overview of Biomaterials

Section 1.2. Properties of Biomaterials

Section 1.3. Classes of Materials Used in Medicine

Section 1.4. Materials Processing

Biology and Medicine

Section 2.1. Some Background Concepts

Section 2.2. Host Reaction to Biomaterials and Their Evaluation

Section 2.3. Characterization of Biomaterials

Section 2.4. Degradation of Materials in the Biological Environment

Section 2.5. Applications of Biomaterials

Section 2.6. Applications of Biomaterials in Functional Tissue Engineering

Part III. The Medical Product Life Cycle

Appendix A.

Copyright

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Chapter 11: Silicones: Copyright © 2020 DuPont, Published by Elsevier Inc. All Rights Reserved.

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Notices

Knowledge and best practice in this field are constantly changing. As new research and experience broaden our understanding, changes in research methods, professional practices, or medical treatment may become necessary.

Practitioners and researchers must always rely on their own experience and knowledge in evaluating and using any information, methods, compounds, or experiments described herein. In using such information or methods they should be mindful of their own safety and the safety of others, including parties for whom they have a professional responsibility.

To the fullest extent of the law, neither the Publisher nor the authors, contributors, or editors, assume any liability for any injury and/or damage to persons or property as a matter of products liability, negligence or otherwise, or from any use or operation of any methods, products, instructions, or ideas contained in the material herein.

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A catalogue record for this book is available from the British Library

ISBN: 978-0-12-816137-1

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List of Contributors

Abhinav Acharya,     School for Engineering of Matter, Transport and Energy, Biodesign Center for Immunotherapy, Vaccines and Virotherapy, Arizona State University, Tempe, AZ, United States

Marian A. Ackun-Farmmer

Department of Biomedical Engineering, University of Rochester, Rochester, NY, United States

Department of Orthopaedics and Center for Musculoskeletal Research, University of Rochester, Rochester, NY, United States

John R. Aggas

Center for Bioelectronics, Biosensors and Biochips (C3B), Department of Biomedical Engineering, Texas A&M University, College Station, TX, United States

Department of Biomedical Engineering, Texas A&M University, College Station, TX, United States

Phillip J. Andersen,     Andersen Metallurgical, LLC, Madison, WI, United States

James M. Anderson,     Department of Pathology, Case Western Reserve University, Cleveland, OH, United States

Kristi Anseth

Department of Chemical and Biological Engineering, University of Colorado, Boulder, CO, United States

Biofrontiers Institute, University of Colorado, Boulder, CO, United States

Paul A. Archer

Parker H. Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, GA, United States

School of Chemical and Biomolecular Engineering, Georgia Institute of Technology, Atlanta, GA, United States

Nureddin Ashammakhi,     Center for Minimally Invasive Therapeutics (C-MIT), California NanoSystems Institute (CNSI), University of California-Los Angeles, Los Angeles, CA, United States

Jose D. Avila,     W. M. Keck Biomedical Materials Research Laboratory, Washington State University, Pullman, WA, United States

Julia E. Babensee,     Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA, United States

Stephen f. Badylak,     University of Pittsburgh, Pittsburgh, PA, United States

Kiheon Baek

Department of Biomedical Engineering, University of Rochester, Rochester, NY, United States

Center for Musculoskeletal Research, University of Rochester Medical Center, Rochester, NY, United States

Aaron B. Baker,     Department of Biomedical Engineering, University of Texas at Austin, Austin, TX, United States

Syeda Mahwish Bakht

3B’s Research Group, I3Bs–Research Institute on Biomaterials, Biodegradables and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, Guimarães, Portugal

ICVS/3B’s–PT Government Associate Laboratory, Braga/Guimarães, Portugal

The Discoveries Centre for Regenerative and Precision Medicine, Headquarters at University of Minho, Guimarães, Portugal

Amit Bandyopadhyay,     W. M. Keck Biomedical Materials Research Laboratory, Washington State University, Pullman, WA, United States

Aaron Barchowsky,     Department of Environmental and Occupational Health, University of Pittsburgh, Pittsburgh, PA, United States

Garrett Bass,     Departments of Chemistry, Mechanical Engineering and Materials Science, Biomedical Engineering and Orthopaedic Surgery, Duke University, Durham, NC, United States

Matthew L. Becker,     Departments of Chemistry, Mechanical Engineering and Materials Science, Biomedical Engineering and Orthopaedic Surgery, Duke University, Durham, NC, United States

Sarah Miho Van Belleghem

University of Maryland College Park

NIH/NIBIB Center for Engineering Complex Tissues

Danielle S.W. Benoit

Department of Biomedical Engineering, University of Rochester, Rochester, NY, United States

Department of Orthopaedics and Center for Musculoskeletal Research, University of Rochester, Rochester, NY, United States

Materials Science Program, University of Rochester, Rochester, NY, United States

Department of Chemical Engineering, University of Rochester, Rochester, NY, United States

Department of Biomedical Genetics and Center for Oral Biology, University of Rochester, Rochester, NY, United States

Translational Biomedical Science Program, University of Rochester, Rochester, NY, United States

Arne Biesiekierski,     School of Engineering, RMIT University, Bundoora, VIC, Australia

Kristen L. Billiar,     Biomedical Engineering Department, Worcester Polytechnic Institute, Worcester, MA, United States

Susmita Bose,     W. M. Keck Biomedical Materials Research Laboratory, Washington State University, Pullman, WA, United States

Christopher Bowman,     Department of Chemical and Biological Engineering, University of Colorado, Boulder, CO, United States

Steven Boyce,     Department of Surgery, University of Cincinnati and Shriners Hospitals for Children – Cincinnati, Cincinnati, OH, United States

Bryan N. Brown

Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA, United States

McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA, United States

Justin L. Brown,     Department of Biomedical Engineering, The Pennsylvania State University, University Park, PA, United States

Jeffrey R. Capadona

Department of Biomedical Engineering, Case Western Reserve University, Cleveland, OH, United States

Advanced Platform Technology Center, Rehabilitation Research and Development, Louis Stokes Cleveland VA Medical Center, Cleveland, OH, United States

David G. Castner,     University of Washington, Seattle, WA, United States

Calvin Chang

Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD, United States

Translational Tissue Engineering Center, Johns Hopkins School of Medicine, Baltimore, MD, United States

Institute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD, United States

Philip Chang,     Department of Surgery, University of Cincinnati and Shriners Hospitals for Children – Cincinnati, Cincinnati, OH, United States

Ashutosh Chilkoti,     Department of Biomedical Engineering, Duke University, Durham, NC, United States

Karen L. Christman,     Department of Bioengineering, Sanford Consortium of Regenerative Medicine, University of California San Diego, La Jolla, CA, United States

Sangwon Chung

Department of Textile Engineering, Chemistry & Science, North Carolina State University, Raleigh, NC, United States

Biomedical Engineering, Joint Department of Biomedical Engineering, North Carolina State University and University of North Carolina at Chapel Hill, Chapel Hill, NC, United States

Kelly P. Coleman,     Medtronic, Physiological Research Laboratories, Minneapolis, MN, United States

Dan Conway,     Department of Biomedical Engineering, Virginia Commonwealth University, Richmond, VA, United States

Keith E. Cook,     Department of Biomedical Engineering, Carnegie Mellon University, Pittsburgh, PA, United States

Stuart L. Cooper,     William G. Lowrie Department of Chemical and Biomolecular Engineering, The Ohio State University, Columbus, OH, United States

Elizabeth Cosgriff-Hernandez,     The University of Texas at Austin, Austin, TX, United States

Arthur J. Coury,     Northeastern University, Boston, MA, United States

Joseph D. Criscione,     Department of Biomedical Engineering, University of Rochester, Rochester, NY, United States

Heidi Culver,     Department of Chemical and Biological Engineering, University of Colorado, Boulder, CO, United States

Jim Curtis,     DuPont Health Care Solutions, Midland, MI, United States

Feiyang Deng,     Department of Biomedical Engineering, University of Rochester, Rochester, NY, United States

Prachi Dhavalikar,     The University of Texas at Austin, Austin, TX, United States

Luis Diaz-Gomez,     Department of Bioengineering, Rice University, Houston, TX, United States

Rui M.A. Domingues

3B’s Research Group, I3Bs–Research Institute on Biomaterials, Biodegradables and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, Guimarães, Portugal

ICVS/3B’s–PT Government Associate Laboratory, Braga/Guimarães, Portugal

The Discoveries Centre for Regenerative and Precision Medicine, Headquarters at University of Minho, Guimarães, Portugal

Elaine Duncan

Paladin Medical, Inc., Stillwater, MN, United States

Joseph Halcomb III, MD. Department of Biomedical Engineering, College of Engineering, University of Kentucky, Lexington, KY, United States

Pamela Duran,     Department of Bioengineering, Sanford Consortium of Regenerative Medicine, University of California San Diego, La Jolla, CA, United States

Pedro Esbrit,     Chemical Department of Pharmaceutical Sciences, Faculty of Pharmacy, Universidad Complutense of Madrid, Spain

Suzanne G. Eskin,     Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, GA, United States

Michael Y. Esmail,     Tufts Comparative Medicine Services, Tufts University, Boston, MA, United States

Jack L. Ferracane,     Department of Restorative Dentistry, Oregon Health & Science University, Portland, OR 97201

Claudia Fischbach

Nancy E. and Peter C. Meinig School of Biomedical Engineering, Cornell University, Ithaca, NY, United States

Kavli Institute at Cornell for Nanoscale Science, Cornell University, Ithaca, NY, United States

Gary Fischman, PhD ,     Future Strategy Solutions, LLC, Gambrills, MD, United States

John P. Fisher

University of Maryland College Park

NIH/NIBIB Center for Engineering Complex Tissues

Iolanda Francolini,     Department of Chemistry, Sapienza University of Rome, Rome, Italy

Steven J. Frey,     School of Chemical and Biomolecular Engineering, Georgia Institute of Technology, Atlanta, GA, United States

Akhilesh K. Gaharwar,     Texas A&M University, College Station, TX, United States

Andrés J. García

George W. Woodruff School of Mechanical Engineering, Georgia Institute of Technology, Atlanta, GA, United States

Parker H. Petit Institute of Bioengineering and Biological Science, Georgia Institute of Technology, Atlanta, GA, United States

Iain R. Gibson,     Institute of Medical Sciences, School of Medicine, Medical Sciences and Nutrition, University of Aberdeen, Aberdeen, United Kingdom

Jeremy L. Gilbert,     Department of Bioengineering, Clemson University, Charleston, SC, United States

Brian Ginn,     Secant Group, Telford, PA, United States

Zachary E. Goldblatt,     Biomedical Engineering Department, Worcester Polytechnic Institute, Worcester, MA, United States

Seth J. Goldenberg,     Veeva Systems, Pleasanton, CA, United States

Manuela E. Gomes

3B’s Research Group, I3Bs–Research Institute on Biomaterials, Biodegradables and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, Guimarães, Portugal

ICVS/3B’s–PT Government Associate Laboratory, Braga/Guimarães, Portugal

The Discoveries Centre for Regenerative and Precision Medicine, Headquarters at University of Minho, Guimarães, Portugal

Manuel Gómez-Florit

3B’s Research Group, I3Bs–Research Institute on Biomaterials, Biodegradables and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, Guimarães, Portugal

ICVS/3B’s–PT Government Associate Laboratory, Braga/Guimarães, Portugal

The Discoveries Centre for Regenerative and Precision Medicine, Headquarters at University of Minho, Guimarães, Portugal

Inês C. Gonçalves

i3S - Instituto de Inovação e Investigação em Saúde, Universidade do Porto, Rua Alfredo Allen 208, Porto, Portugal

INEB - Instituto de Engenharia Biomédica, Universidade do Porto, Rua Alfredo Allen 208, Porto, Portugal

Maud B. Gorbet,     Department of Systems Design Engineering, University of Waterloo, ON, Canada

David W. Grainger

Department of Biomedical Engineering, University of Utah, Salt Lake City, UT, United States

Department of Pharmaceutics and Pharmaceutical Chemistry, University of Utah, Salt Lake City, UT, United States

Miles Grody,     Miles Grody Law, Potomac, MD, United States

Teja Guda,     Department of Biomedical Engineering, University of Texas at San Antonio, San Antonio, TX, United States

Scott A. Guelcher,     Department of Chemical and Biomolecular Engineering, Vanderbilt University, Nashville, TN, United States

Anthony Guiseppi-Elie

Center for Bioelectronics, Biosensors and Biochips (C3B), Department of Biomedical Engineering, Texas A&M University, College Station, TX, United States

Department of Biomedical Engineering, Texas A&M University, College Station, TX, United States

ABTECH Scientific, Inc., Biotechnology Research Park, Richmond, VA, United States

S. Adam Hacking,     Laboratory for Musculoskeletal Research and Innovation, Department of Orthopaedic Surgery, Massachusetts General Hospital and Harvard Medical School, Boston, MA, United States

Nadim James Hallab,     Department of Orthopedic Surgery, Rush University Medical Center, Chicago, IL, United States

Luanne Hall-Stoodley,     Department of Microbial Infection and Immunity, The Ohio State University, Columbus, OH, United States

Stephen R. Hanson,     Division of Biomedical Engineering, School of Medicine, Oregon Health & Science University, Portland, OR, United States

Woojin M. Han

George W. Woodruff School of Mechanical Engineering, Georgia Institute of Technology, Atlanta, GA, United States

Parker H. Petit Institute of Bioengineering and Biological Science, Georgia Institute of Technology, Atlanta, GA, United States

Melinda K. Harman,     Department of Bioengineering, Clemson University, Clemson, SC, United States

Roger Harrington,     Medical Products Development Director, Medtronic, Boston, MA, United States

Martin J. Haschak

Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA, United States

McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA, United States

Daniel E. Heath,     William G. Lowrie Department of Chemical and Biomolecular Engineering, The Ohio State University, Columbus, OH, United States

Emily Anne Hicks,     Department of Chemical Engineering, McMaster University, Hamilton, ON, Canada

Ryan T. Hill,     Center for Biologically Inspired Materials and Material Systems, Duke University, Durham, NC, United States

Allan S. Hoffman,     Bioengineering and Chemical Engineering, University of Washington, Seattle, WA, United States

Thomas A. Horbett,     Bioengineering and Chemical Engineering, University of Washington, Seattle, WA, United States

Jeffrey A. Hubbell,     The University of Chicago, Chicago, IL, United States

Rasim Ipek,     Department of Mechanical Engineering, Ege University, Izmir, Turkey

Joshua J. Jacobs,     Department of Orthopedic Surgery, Rush University Medical Center, Chicago, IL, United States

Young C. Jang

School of Biological Sciences, Georgia Institute of Technology, Atlanta, GA, United States

Parker H. Petit Institute of Bioengineering and Biological Science, Georgia Institute of Technology, Atlanta, GA, United States

Shaoyi Jiang,     Departments of Chemical Engineering and Bioengineering, Seattle, WA, United States

Richard J. Johnson,     BioPhia Consulting, Lake Forest, IL, United States

Julian R. Jones,     Department of Materials, Imperial College London, South Kensington Campus, London, United Kingdom

Vickie Y. Jo,     Department of Pathology, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, United States

Ravi S. Kane,     School of Chemical and Biomolecular Engineering, Georgia Institute of Technology, Atlanta, GA, United States

David L. Kaplan,     Department of Biomedical Engineering, Tufts University, Medford, MA, United States

Ronit Kar,     The University of Texas at Austin, Austin, TX, United States

Benjamin George Keselowsky,     Department of Biomedical Engineering, University of Florida, Gainesville, FL, United States

Ali Khademhosseini,     Center for Minimally Invasive Therapeutics (C-MIT), California NanoSystems Institute (CNSI), University of California-Los Angeles, Los Angeles, CA, United States

Yu Seon Kim,     Department of Bioengineering, Rice University, Houston, TX, United States

Martin W. King,     Department of Textile Engineering, Chemistry & Science, North Carolina State University, Raleigh, NC, United States

Daniel S. Kohane,     Laboratory for Biomaterials and Drug Delivery, Department of Anesthesiology, Division of Critical Care Medicine, Boston Children’s Hospital, Harvard Medical School, Boston, MA, United States

David H. Kohn,     Departments of Biologic and Materials Sciences, and Biomedical Engineering, The University of Michigan, Ann Arbor, MI, United States

Liisa T. Kuhn,     Department of Biomedical Engineering, University of Connecticut Health Center, Farmington, CT, United States

Mangesh Kulkarni

Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA, United States

McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA, United States

Catherine K. Kuo

Department of Biomedical Engineering, University of Rochester, Rochester, NY, United States

Center for Musculoskeletal Research, University of Rochester Medical Center, Rochester, NY, United States

Department of Orthopaedics, University of Rochester Medical Center, Rochester, NY, United States

Angela Lai,     Department of Biomedical Engineering, Carnegie Mellon University, Pittsburgh, PA, United States

Bryron Lambert,     Sterilization Science, Abbott Vascular, Temecula, CA, United States

Ziyang Lan,     The University of Texas at Austin, Austin, TX, United States

Robert A. Latour,     Bioengineering Department, Clemson University, Clemson, SC, United States

Cato T. Laurencin,     Department of Biomedical Engineering, The Pennsylvania State University, University Park, PA, United States

Bryan K. Lawson, M.D. ,     Department of Orthopaedic Surgery, Mike O’Callaghan Military Medical Center, Nellis AFB, NV, United States

Shannon Lee Layland,     Department of Women’s Health, Research Institute for Women’s Health, Eberhard Karls University Tübingen, Tübingen, Germany

Jae Sung Lee,     Department of Orthopedics and Rehabilitation, University of Wisconsin–Madison, Madison, WI, United States

David Lee-Parritz,     Department of Environmental and Population Health, Tufts University Cummings School of Veterinary Medicine, North Grafton, MA, United States

Ying Lei,     Biomedical Engineering Department, Worcester Polytechnic Institute, Worcester, MA, United States

Jack E. Lemons,     Schools of Dentistry, Medicine and Engineering, University of Alabama at Birmingham, Birmingham, AL, United States

Robert J. Levy,     Department of Pediatrics, The Childrens’ Hospital of Philadelphia, The Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, United States

Gregory M. Lewerenz,     Medtronic, Physiological Research Laboratories, Minneapolis, MN, United States

Jamal S. Lewis,     Biomedical Engineering, University of California Davis, CA, United States

Simone Liebscher,     Department of Women’s Health, Research Institute for Women’s Health, Eberhard Karls University Tübingen, Tübingen, Germany

Chien-Chi Lin,     Department of Biomedical Engineering, Indiana University-Purdue University Indianapolis, Indianapolis, IN, United States

Natalie K. Livingston

Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD, United States

Translational Tissue Engineering Center, Johns Hopkins School of Medicine, Baltimore, MD, United States

Institute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD, United States

Yang Li,     Laboratory for Biomaterials and Drug Delivery, Department of Anesthesiology, Division of Critical Care Medicine, Boston Children’s Hospital, Harvard Medical School, Boston, MA, United States

Yuncang Li,     School of Engineering, RMIT University, Bundoora, VIC, Australia

Helen Lu,     Department of Biomedical Engineering, Columbia University, New York, NY, United States

Laura Macdougall

Department of Chemical and Biological Engineering, University of Colorado, Boulder, CO, United States

Biofrontiers Institute, University of Colorado, Boulder, CO, United States

Bhushan Mahadik

University of Maryland College Park

NIH/NIBIB Center for Engineering Complex Tissues

Sachin Mamidwar,     Orthogen, LLC, Springfield, NJ, United States

Margaret P. Manspeaker

Parker H. Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, GA, United States

School of Chemical and Biomolecular Engineering, Georgia Institute of Technology, Atlanta, GA, United States

Hai-Quan Mao

Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD, United States

Translational Tissue Engineering Center, Johns Hopkins School of Medicine, Baltimore, MD, United States

Institute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD, United States

Department of Materials Science and Engineering, Johns Hopkins University, Baltimore, MD, United States

Peter X. Ma,     Department of Biologic and Materials Science, School of Dentistry, University of Michigan, Ann Arbor, MI, United States

Tyler Marcet,     Department of Biomedical Engineering, Tufts University, Medford, MA, United States

Jeffrey Martin,     President and Principal Consultant, Sterilization and Quality System Consulting LLC, Dallas, TX, United States

M. Cristina L. Martins,     INEB - Institute of Biomedical Engineering, University of Porto, Porto, Portugal

Sally L. McArthur

Bioengineering Research Group, Swinburne University of Technology, Melbourne, VIC, Australia

Biomedical Manufacturing, CSIRO Manufacturing, Melbourne, VIC, Australia

Meghan McGill,     Department of Biomedical Engineering, Tufts University, Medford, MA, United States

Larry V. McIntire,     Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, GA, United States

Lei Mei,     Department of Biomedical Engineering, University of Texas at Austin, Austin, TX, United States

Bárbara B. Mendes

3B’s Research Group, I3Bs–Research Institute on Biomaterials, Biodegradables and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, Guimarães, Portugal

ICVS/3B’s–PT Government Associate Laboratory, Braga/Guimarães, Portugal

The Discoveries Centre for Regenerative and Precision Medicine, Headquarters at University of Minho, Guimarães, Portugal

Antonios G. Mikos,     Department of Bioengineering, Rice University, Houston, TX, United States

Richard N. Mitchell,     Department of Pathology/Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, United States

Indranath Mitra,     W. M. Keck Biomedical Materials Research Laboratory, Washington State University, Pullman, WA, United States

Ben Muirhead,     Department of Chemical Engineering, McMaster University, Hamilton, ON, Canada

Khurram Munir,     School of Engineering, RMIT University, Bundoora, VIC, Australia

William L. Murphy

Department of Orthopedics and Rehabilitation, University of Wisconsin–Madison, Madison, WI, United States

Department of Biomedical Engineering, University of Wisconsin–Madison, Madison, WI, United States

Phong K. Nguyen

Department of Biomedical Engineering, University of Rochester, Rochester, NY, United States

Center for Musculoskeletal Research, University of Rochester Medical Center, Rochester, NY, United States

Alexis L. Nolfi

Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA, United States

McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA, United States

Clyde Overby

Department of Biomedical Engineering, University of Rochester, Rochester, NY, United States

Department of Orthopaedics and Center for Musculoskeletal Research, University of Rochester, Rochester, NY, United States

Sertan Ozan

School of Engineering, RMIT University, Bundoora, VIC, Australia

Department of Mechanical Engineering, Yozgat Bozok University, Yozgat, Turkey

Robert F. Padera,     Department of Pathology/Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, United States

Hannah A. Pearce,     Department of Bioengineering, Rice University, Houston, TX, United States

Nicholas A. Peppas,     Department of Chemical Engineering and Biomedical Engineering, Pediatrics, Surgery and Molecular Pharmaceutics and Drug Delivery, The University of Texas, Austin, TX, United States

Andreia T. Pereira

i3S - Instituto de Inovação e Investigação em Saúde, Universidade do Porto, Rua Alfredo Allen 208, Porto, Portugal

INEB - Instituto de Engenharia Biomédica, Universidade do Porto, Rua Alfredo Allen 208, Porto, Portugal

Graduate Program in Areas of Basic and Applied Biology, Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, Rua Jorge de Viterbo Ferreira 228, Porto, Portugal

Carmem S. Pfeifer,     Biomaterials and Biomechanics, Oregon Health & Science University, Portland, OR, 97201

Artur M. Pinto,     LEPABE – Laboratory of Process Engineering, Environment, Biotechnology and Energy, Faculty of Engineering, University of Porto, Portugal

Nicole R. Raia,     Department of Biomedical Engineering, Tufts University, Medford, MA, United States

Edward A. Rankin,     Medtronic, Physiological Research Laboratories, Minneapolis, MN, United States

Buddy D. Ratner,     Bioengineering and Chemical Engineering, Director of University of Washington Engineered Biomaterials (UWEB), Seattle, WA, United States

Maria Vallet Regi,     Chemical Department of Pharmaceutical Sciences, Faculty of Pharmacy, Universidad Complutense of Madrid, Spain

Rui L. Reis

3B’s Research Group, I3Bs–Research Institute on Biomaterials, Biodegradables and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, Guimarães, Portugal

ICVS/3B’s–PT Government Associate Laboratory, Braga/Guimarães, Portugal

The Discoveries Centre for Regenerative and Precision Medicine, Headquarters at University of Minho, Guimarães, Portugal

Alastair Campbell Ritchie,     Department of Mechanical, Materials and Manufacturing Engineering, University of Nottingham, Nottingham, United Kingdom

Shelly E. Sakiyama-Elbert,     Department of Biomedical Engineering, The University of Texas at Austin, Austin, TX, United States

Karim Salhadar,     The University of Texas at Austin, Austin, TX, United States

Antonio J. Salinas,     Chemical Department of Pharmaceutical Sciences, Faculty of Pharmacy, Universidad Complutense of Madrid, Spain

Katja Schenke-Layland

Department of Women’s Health, Research Institute for Women’s Health, Eberhard Karls University Tübingen, Tübingen, Germany

Natural and Medical Sciences Institute (NMI) at the University of Tübingen, Reutlingen, Germany

Cluster of Excellence iFIT (EXC 2180) Image-Guided and Functionally Instructed Tumor Therapies, Eberhard Karls University Tübingen, Tübingen, Germany

Department of Medicine/Cardiology, Cardiovascular Research Laboratories (CVRL), University of California (UCLA), Los Angeles, CA, United States

Frederick J. Schoen,     Department of Pathology/Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, United States

Brittany E. Schutrum,     Nancy E. and Peter C. Meinig School of Biomedical Engineering, Cornell University, Ithaca, NY, United States

Michael V. Sefton,     Department of Chemical Engineering and Applied Chemistry, Institute of Biomaterials and Biomedical Engineering, University of Toronto, ON, Canada

Michael A. Seidman,     Department of Pathology/Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, United States

Darshan S. Shah, M.D. ,     Department of Orthopaedic Surgery, San Antonio Military Medical Center, Ft Sam Houston, TX, United States

Heather Sheardown,     Department of Chemical Engineering, McMaster University, Hamilton, ON, Canada

Andrew J. Shoffstall

Department of Biomedical Engineering, Case Western Reserve University, Cleveland, OH, United States

Advanced Platform Technology Center, Rehabilitation Research and Development, Louis Stokes Cleveland VA Medical Center, Cleveland, OH, United States

Carl G. Simon, Jr. ,     Biosystems Biomaterials Division, National Institute of Standards & Technology, Gaithersburg, MD, United States

Josh Simon,     Spiral Medical Development, Lansdale, PA, United States

Kenneth R. Sims Jr.

Department of Biomedical Engineering, University of Rochester, Rochester, NY, United States

Translational Biomedical Science Program, University of Rochester, Rochester, NY, United States

Steven M. Slack †

Benjamin Slavin

Translational Tissue Engineering Center, Johns Hopkins School of Medicine, Baltimore, MD, United States

Department of Plastic and Reconstructive Surgery, Johns Hopkins School of Medicine, Baltimore, MD, United States

Kirstie Lane Snodderly

University of Maryland College Park

NIH/NIBIB Center for Engineering Complex Tissues

Patrick S. Stayton,     Bioengineering, University of Washington, Seattle, WA, United States

Stephanie D. Steichen,     DuPont Health Care Solutions, Midland, MI, United States

Paul Stoodley

Department of Microbial Infection and Immunity, The Ohio State University, Columbus, OH, United States

Departments of Orthopaedics and Microbiology, The Ohio State University, Columbus, OH, United States

Campus Imaging and Microscopy Facility, Office of Research, The Ohio State University, Columbus, OH, United States

National Centre for Advanced Tribology, Mechanical Engineering, University of Southampton, Southampton, United Kingdom

W. Benton Swanson,     Department of Biologic and Materials Science, School of Dentistry, University of Michigan, Ann Arbor, MI, United States

Hobey Tam,     Department of Bioengineering, Rhodes Engineering Research Center, Clemson University, Clemson, SC, United States

Aftab Tayab,     Department of Chemical Engineering, McMaster University, Hamilton, ON, Canada

Susan N. Thomas

Parker H. Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, GA, United States

George W. Woodruff School of Mechanical Engineering, Georgia Institute of Technology, Atlanta, GA, United States

Kellen D. Traxel,     W. M. Keck Biomedical Materials Research Laboratory, Washington State University, Pullman, WA, United States

Rocky S. Tuan,     Institute for Tissue Engineering and Regenerative Medicine, The Chinese University of Hong Kong, Hong Kong, SAR, China

Erik I. Tucker,     Division of Biomedical Engineering, School of Medicine, Oregon Health & Science University, Portland, OR, United States

Rei Ukita,     Department of Biomedical Engineering, Carnegie Mellon University, Pittsburgh, PA, United States

Austin Veith,     Department of Biomedical Engineering, University of Texas at Austin, Austin, TX, United States

Sarah E. Vidal Yucha,     Department of Biomedical Engineering, Tufts University, Medford, MA, United States

Christopher Viney,     School of Engineering, University of California at Merced, Merced, CA, United States

Naren Vyavahare,     Department of Bioengineering, Rhodes Engineering Research Center, Clemson University, Clemson, SC, United States

William R. Wagner,     Departments of Surgery, Bioengineering & Chemical Engineering, McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA, United States

Min Wang,     Department of Mechanical Engineering, The University of Hong Kong, Pok Fu Lam, Hong Kong, China

Raymond M. Wang,     Department of Bioengineering, Sanford Consortium of Regenerative Medicine, University of California San Diego, La Jolla, CA, United States

Petra Warner,     Department of Surgery, University of Cincinnati and Shriners Hospitals for Children – Cincinnati, Cincinnati, OH, United States

Cuie Wen,     School of Engineering, RMIT University, Bundoora, VIC, Australia

Jennifer L. West,     Duke University, Durham, NC, United States

Matthew A. Whitman,     Nancy E. and Peter C. Meinig School of Biomedical Engineering, Cornell University, Ithaca, NY, United States

Frank Witte,     Department of Prosthodontics, Geriatric Dentistry and Craniomandibular Disorders, Berlin, Germany

Michael F. Wolf,     Medtronic, Corporate Science and Technology, Minneapolis, MN, United States

Zhicheng Yao

Translational Tissue Engineering Center, Johns Hopkins School of Medicine, Baltimore, MD, United States

Institute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD, United States

Department of Materials Science and Engineering, Johns Hopkins University, Baltimore, MD, United States

Michael Yaszemski, M.D. ,     Department of Orthopaedic Surgery, Mayo Clinic, Rochester, MN, United States

Michael J. Yaszemski,     Orthopaedic Surgery and Biomedical Engineering, Mayo Clinic College of Medicine, Rochester, MN, United States

Lichen Yin,     Jiangsu Key Laboratory for Carbon-Based Functional Materials and Devices, Institute of Functional Nano and Soft Materials (FUNSOM), the Collaborative Innovation Center of Suzhou Nano Science and Technology, Soochow University, Suzhou, Jiangsu, China

Guigen Zhang,     F Joseph Halcomb III, M.D. Department of Biomedical Engineering, University of Kentucky, Lexington, KY, United States

Peng Zhang,     Department of Chemical Engineering, University of Washington, Seattle, WA, United States

Zhiyuan Zhong,     Biomedical Polymers Laboratory and Jiangsu Key Laboratory of Advanced Functional Polymer Design and Application, College of Chemistry, Chemical Engineering and Materials Science, Soochow University, Suzhou, Jiangsu, China

Nicholas P. Ziats, Ph.D. ,     Pathology, Biomedical Engineering & Anatomy Vice Chair of Pathology for Academic Affairs Case Western Reserve University Department of Pathology Cleveland, Ohio

---

†  

†Deceased.

Preface

Biomaterials Science: An Introduction to Materials in Medicine was launched as an educational project to provide a nascent biomaterials community with an authoritative tool for training and education. Conceptual background material and a broad overview of applications were both envisioned as being integral to the textbook. In the late 1980s, biomaterials was in transition from an emerging field to a respected discipline embracing convergence (i.e., the merging of expertise from different silos, such as provided by engineers, biomedical scientists, and physicians)—the biomaterials community was in need of an integrated, comprehensive, and definitive educational resource. This rationale for launching the textbook has been validated by the success of the first three editions of Biomaterials Science: An Introduction to Materials in Medicine. With well over 33,000 print copies, numerous online readers through institutional subscriptions, and the thousands who have bought the e-book version, the text has made consequential contributions to the biomaterials education of students and researchers around the world. The previous editions have been widely adopted for classroom use and serve as a reference resource for thousands of biomaterials professionals.

Biomaterials Science: An Introduction to Materials in Medicine strives for a balanced view of the biomaterials field. When this project was first launched, monographs available at that time did articulately address biomaterials, but they tended to strongly emphasize the authors’ areas of expertise, while only superficially addressing other important subjects outside of their intellectual sphere. Balanced presentation means appropriate representation of:

• hard and soft biomaterials, with coverage of all major material classes both synthetic and biologically derived;

• the common application areas, including orthopedic, cardiovascular, ophthalmologic, dental, and emerging applications;

• a balance of fundamental biological and materials science concepts, contemporary medical/clinical concerns, and regulatory/commercial/societal issues that reflect the complex environment in which biomaterials are developed and used;

• coverage of the past, present, and future of biomaterials, their applications, and key challenges that lie ahead.

In this way, the reader can embrace the broad field, absorb the unifying principles common to all materials in contact with biological systems, and gain a solid appreciation for the special significance of the word biomaterial.

Biomaterials Science: An Introduction to Materials in Medicine, fourth edition, strives for curricular cohesion. By integrating the experience of many leaders in the biomaterials field, we endeavor to present a balanced yet comprehensive perspective on an exciting and rapidly evolving discipline—and present this information in a graphically attractive and readable format, intended to be useful as an educational resource to a broad array of students, teachers, and practicing professionals.

With this fourth edition a new set of four editors has taken on the challenge of moving the textbook forward. It is a humbling task to take over editor responsibilities from the four pioneers and visionaries in the field who launched the text and thoughtfully guided what became the quintessential biomaterials textbook through three editions. The new editor team recognized that the book could not physically grow any further than the size of the third edition (as any student who has carried that edition for a semester in a backpack would appreciate). Thus a balanced approach had to be implemented to both grow and cut back. Furthermore, with broad adoption of online access, the opportunity to place some supplementary content online was utilized (e.g., end-of-chapter questions and a further reading section).

First and foremost, the new editors wished to retain continuity with previous editions of the text and changed little where revision was not required. Moderate updates were made in many chapters, often keeping existing author teams and enlisting new coauthors. However, where a fresh direction seemed appropriate for a chapter given the state of the science, or the introduction of new chapters was indicated for where the field had expanded, new author teams were recruited. Overall there are 17 new chapters and 43 chapters with a new set of authors. To balance this growth, some topics were consolidated. A change the reader may notice in content is that the editors have elected to reduce the depth of emphasis on tissue engineering and some device topics, believing that there are now excellent texts devoted exclusively to the maturing tissue engineering field. With medical devices, the desire was not only to cover the critical application areas in overview and to include major new advances, but also to recognize that readers will be able to find field-specific, in-depth device coverage elsewhere. Finally, particular attention was given to the third section of the book, where guidance is provided that seeks to prepare the reader for the development pathway beyond the demonstration of a proof-of-concept. Here our hope was that the disconnect between the vast biomaterials scientific literature and the reality of what devices are used clinically and how they are implemented can be appreciated. Such understanding is critical if scientific advances are to ultimately reach the target patient population.

The founding editors are still very much a part of this textbook. They have provided wise counsel as the new editors developed the plan for the fourth edition, but also authored revisions in several chapters from previous editions. Much of the excellent content and perspective that has made this text so useful to the community has come from the writings of the founding editors. We have sought to preserve and update this valued content.

Acknowledgments and thanks are in order. First, the Society for Biomaterials (SFB), sponsor and inspiration for this book, is a model of multidisciplinary cultural diversity. Composed of engineers, physicians, scientists, veterinarians, industrialists, inventors, regulators, attorneys, educators, ethicists, and others, the SFB provides the nidus for the intellectually exciting, humanistically relevant, and economically important biomaterials field. As was the case for all of the previous editions, the editors recognize the importance of the SFB by donating all royalties from sales of this volume to the Society, to directly support education and career development related to biomaterials. For information on the SFB, visit the SFB website at http://www.biomaterials.org/.

We offer special thanks to those who have generously invested time, energy, experience, and intelligence to author the chapters of this textbook. The over 100 scientists, physicians, engineers, and industry leaders who contributed their expertise and perspectives are clearly the backbone of this work, and they deserve high praise—their efforts will strongly impact the education of the next generation of biomaterials scientists. It is only with such a distinguished group of authors that this text can provide the needed balance, scope, and perspective. We also pay respect and homage to biomaterials pioneers who have contributed to this or previous editions, but have since passed on; their contributions and collegiality are remembered and will be missed.

The organizational skills, experience, and encouragement of the staff at Elsevier Publishers have led this fourth edition from a broad and complex challenge to a valuable volume—a tangible resource for the community. Thank you, Elsevier, for this contribution to the field of biomaterials.

The biomaterials field, since its inception in the 1950s, has been ripe with opportunity, intellectual stimulation, compassion, creativity, and rich collaboration. In this field we look to the horizons where the new ideas from science, technology, and medicine arise. Importantly, we strive to improve the survival and quality of life for billions through biomaterials-based medical devices and treatments. We, the new editors, together with the founding editors hope that the biomaterials textbook you are now reading will stimulate you as much as it has us.

William R. Wagner

Shelly E. Sakiyama-Elbert

Guigen Zhang

Michael J. Yaszemski

Founding Editors:

Buddy D. Ratner

Allan S. Hoffman

Frederick J. Schoen

Jack E. Lemons

March, 2020

How to Use this Book

Biomaterials Science: An Introduction to Materials in Medicine, fourth edition, was conceived as a learning tool to compatibilize through common language and fundamental principles, a number of independent communities (basic sciences, engineering, medicine, dentistry, industry, regulatory, legal, etc.). Although the book has 98 chapters, 4 appendices, there is a logic of organization and curriculum that should make the book straightforward to use in an academic course or as a reference work.

A guiding principle in assembling this multiauthor, multidisciplinary textbook is that fundamental and translational progress in the field of biomaterials necessitates integration of concepts and tools from the full spectrum of the physical sciences, engineering, clinical medicine, biology, and life sciences. Indeed, the discipline of biomaterials utilizes a convergence of multidisciplinary elements to enable the development of specific diagnostic or therapeutic devices—i.e., using biomaterials science and technology to create and implement real medical devices and other products that solve clinical problems and improve patient outcomes. Nevertheless, the editors believe (and the book has been assembled so) that a physician should be able to pick up the textbook and glean a baseline knowledge of the science, engineering, and commercialization aspects of biomaterials. A chemist could use this book to appreciate the biology behind biomaterials, the physiology associated with medical devices, and the applications in medicine. An engineer hired by a medical device company might learn the basic science underlying the technological development and details on medical applications. Similarly, for other disciplines that interface with biomaterials, this book can guide the reader through diverse but related topics that are generally not found in one volume.

The textbook has well over 100 authors. The field of biomaterials is so diverse in subject matter that a guiding principle has been that no one author can write it all—let us use the experience and wisdom of acknowledged masters of each subject to communicate the best information to the reader. But, to prevent this book from appearing to be simply a collection of review papers, considerable editorial effort has gone into ensuring logical curricular organization, continuity of ideas, and extensive cross-referencing between chapters.

Biomaterials Science: An Introduction to Materials in Medicine, fourth edition, is divided into three parts: Materials Science and Engineering, Biology and Medicine, and The Medical Product Life Cycle. Sections then serve to subdivide each of these three parts (for example, under the part called Materials Science and Engineering there are sections on properties of materials and classes of materials used in medicine). And finally, within these sections can be found chapters, for example, on the major types of materials that are used in medicine (hydrogels, polyurethanes, titanium alloys, etc.). Each section begins with an introduction by one of the editors that will guide the reader through the chapters, giving cohesion to the sections and highlighting key issues that are worthy of attention. Finally, there are appendices that tabulate useful data and information.

For most chapters, exercises are provided for classroom use and for self-testing. These can be accessed via the companion website at https://www.elsevier.com/books-and-journals/book-companion/9780128161371. This site makes it possible to update problems and add new ones, and provides other resource materials, including a full artwork catalog and downloadable images used in the text. For instructors, solutions to the end-of-chapter exercises are provided on an Instructor Site at http://textbooks.elsevier.com/web/Manuals.aspx?isbn=9780128161371.

We hope that the textbook organization, the extensive editorial effort, and the expertly authored chapters will serve their intended purpose—to guide the reader into and through this complex field of biomaterials science. The editors always appreciate feedback and commentary—contact information is provided for them.

And now it is time to delve into the rich world of biomaterials science.

Materials Science and Engineering

Outline

Section 1.1. Overview of Biomaterials

Introduction to Biomaterials Science: An Evolving, Multidisciplinary Endeavor

A History of Biomaterials

Section 1.2. Properties of Biomaterials

Introduction: Properties of Materials— the Palette of the Biomaterials Engineer

The Nature of Matter and Materials

Bulk Properties of Materials

Surface Properties and Surface Characterization of Biomaterials

Role of Water in Biomaterials

Section 1.3. Classes of Materials Used in Medicine

The Materials Side of the Biomaterials Relationship

Polymers: Basic Principles

Polyurethanes

Silicones

Fluorinated Biomaterials

The Organic Matrix of Restorative Composites and Adhesives

Hydrogels

Degradable and Resorbable Polymers

Applications of Smart Polymers as Biomaterials

Metals: Basic Principles

Titanium Alloys, Including Nitinol

Stainless Steels

CoCr Alloys

Biodegradable Metals

Ceramics, Glasses, and Glass-Ceramics: Basic Principles

Natural and Synthetic Hydroxyapatites

Structural Ceramic Oxides

Carbon Biomaterials

Natural Materials

Processed Tissues

Use of Extracellular Matrix Proteins and Natural Materials in Bioengineering

Composites

Microparticles

Nanoparticles

Section 1.4. Materials Processing

Introduction to Materials Processing for Biomaterials

Physicochemical Surface Modification of Materials Used in Medicine

Nonfouling Surfaces

Nonthrombogenic Treatments and Strategies

Surface-Immobilized Biomolecules

Surface Patterning

Medical Fibers and Biotextiles

Textured and Porous Biomaterials

Biomedical Applications of Additive Manufacturing

Section 1.1

Overview of Biomaterials

Outline

Introduction to Biomaterials Science: An Evolving, Multidisciplinary Endeavor

A History of Biomaterials

1.1.1

Introduction to Biomaterials Science

An Evolving, Multidisciplinary Endeavor

Buddy D. Ratner ¹ , Allan S. Hoffman ² , Frederick J. Schoen ³ , Jack E. Lemons ⁴ , William R. Wagner ⁵ , Shelly E. Sakiyama-Elbert ⁶ , Guigen Zhang ⁷ , and Michael J. Yaszemski ⁸       ¹ Bioengineering and Chemical Engineering, Director of University of Washington Engineered Biomaterials (UWEB), Seattle, WA, United States      ² Bioengineering and Chemical Engineering, University of Washington, Seattle, WA, United States      ³ Department of Pathology, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, United States      ⁴ Schools of Dentistry, Medicine and Engineering, University of Alabama at Birmingham, Birmingham, AL, United States      ⁵ Departments of Surgery, Bioengineering & Chemical Engineering, McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA, United States      ⁶ Department of Biomedical Engineering, The University of Texas at Austin, Austin, TX, United States      ⁷ F Joseph Halcomb III, M.D. Department of Biomedical Engineering, University of Kentucky, Lexington, KY, United States      ⁸ Orthopaedic Surgery and Biomedical Engineering, Mayo Clinic College of Medicine, Rochester, MN, United States

Biomaterials and Biomaterials Science

Biomaterials Science: An Introduction to Materials in Medicine, fourth edition, addresses the design, fabrication, testing, applications, and performance as well as nontechnical considerations integral to the translation of synthetic and natural materials that are used in a wide variety of implants, devices, and process equipment that contact biological systems. These materials are referred to as biomaterials.

The compelling, human side to biomaterials is that millions of lives are saved, and the quality of life is improved for millions more.

The field of biomaterials is some 70–80 years old at the time of publication of this fourth edition. It significantly impacts human health, the economy, and many scientific fields. Biomaterials and the medical devices comprised of them are now commonly used as prostheses in cardiovascular, orthopedic, dental, ophthalmological, and reconstructive surgery, and in other interventions such as surgical sutures, bioadhesives, and controlled drug release devices. The compelling, human side to biomaterials is that millions of lives have been saved, and the quality of life improved for millions more, based on devices fabricated from biomaterials. The biomaterials field has seen accelerating growth since the first medical devices that were based on accepted medical and scientific principles made their way into human usage in the late 1940s and early 1950s. And the growth of the field is ensured, with the aging population, the increasing standard of living in developing countries, and the growing ability to address previously untreatable medical conditions.

Figure 1.1.1.1 The path from the basic science of biomaterials, to a medical device, to clinical application.

Biomaterials science addresses both therapeutics and diagnostics. It encompasses basic sciences (biology, chemistry, physics) and engineering and medicine. The translation of biomaterials science to clinically important medical devices is dependent on: (1) sound engineering design; (2) testing in vitro, in animals and in humans; (3) clinical realities; and (4) the involvement of industry permitting product development and commercialization. Fig. 1.1.1.1 schematically illustrates the path from scientific development to the clinic.

Biomaterials science, in its modern incarnation, is an example of the emerging convergence paradigm that pushes multidisciplinary collaboration among experts and multidisciplinary integration of concepts and practice (Sharp and Langer, 2011). Not only biomaterials, but also bioinformatics, synthetic biology, computational biology, nanobiology, systems biology, molecular biology, and other forefront fields depend on convergence for their continued progress. This textbook aims to introduce these diverse multidisciplinary elements, particularly focusing on interrelationships rather than disciplinary boundaries, to systematize the biomaterials subject into a cohesive curriculum—a true convergence.

The title of this textbook, Biomaterials Science: An Introduction to Materials in Medicine, is accurate and descriptive. The intent of this work is: (1) to focus on the scientific and engineering fundamentals behind biomaterials and their applications; (2) to provide sufficient background knowledge to guide the reader to a clear understanding and appreciation of the clinical context where biomaterials are applied; and (3) to highlight the opportunities and challenges in the field. Every chapter in this text can serve as a portal to an extensive contemporary literature that expands on the basic ideas presented here. The magnitude of the biomaterials endeavor, its broadly integrated multidisciplinary scope, and examples of biomaterials applications will be revealed in this introductory chapter and throughout the book.

The common thread in biomaterials is the physical and chemical interactions between complex biological systems and synthetic or modified natural materials.

Although biomaterials are primarily used for medical applications (the focus of this text), they are also used to grow cells in culture, to assay for blood proteins in the clinical laboratory, in processing equipment for biotechnological applications, for implants to regulate fertility in cattle, in diagnostic gene arrays, in the aquaculture of oysters, and for investigational cell–silicon neuronal computers. How do we reconcile these diverse uses of materials into one field? The common thread is the physical and chemical interactions between complex biological systems and synthetic materials or modified natural materials.

In medical applications, biomaterials are rarely used as isolated materials, but are more commonly integrated into devices or implants, and complex devices may use multiple biomaterials, often selected from several classes (e.g., metal and polymer). Chemically pure titanium can be called a biomaterial, but shaped (machined) titanium in conjunction with ultrahigh molecular weight polyethylene becomes the device, a hip prosthesis. Although this is a text on biomaterials, it will quickly become apparent that the subject cannot be explored without also considering biomedical devices and the biological response to them. Indeed, both the material and the device impact the recipient (patient) and, as we will see, the patient’s host tissue impacts the device. These interactions can lead to device success or, where there is inappropriate choice of biomaterials or poor device design, device failure. Moreover, specific patient characteristics may influence the propensity to failure (e.g., obesity increasing the likelihood of fracture or excessive wear of a hip joint prosthesis, or clotting of a mechanical heart valve in a patient with a genetic mutation that causes hyper-coagulability).

Furthermore, a biomaterial must always be considered in the context of its final fabricated, sterilized form. For example, when a polyurethane elastomer is cast from a solvent onto a mold to form the pump bladder of a heart assist device, it can elicit different blood reactions compared to when injection molding is used to form the same device. A hemodialysis system serving as an artificial kidney requires materials that must function in contact with a patient’s blood, and also exhibit appropriate membrane permeability and mass transport characteristics. Much fabrication technology is applied to convert the biomaterials of the hemodialysis system (polysulfone, silicone rubber, polyethylene) into the complex apparatus that is used for blood purification.

Due to space limitations and the materials focus of this work, many aspects of medical device design are not addressed in this book. Consider the example of the hemodialysis system. This textbook will overview membrane materials and their biocompatibility; there will be little coverage of mass transport through membranes, the burst strength of membranes, dialysate water purification, pumps, flow systems, and monitoring electronics. Other books and articles cover these topics in detail, and chapter authors provide references useful to learn more about topics not explicitly covered.

Key Definitions

The words biomaterial and biocompatibility have already been used in this introduction without formal definition. A few definitions and descriptions are in order, and will be expanded upon in this and subsequent chapters.

A definition of biomaterial endorsed by a consensus of experts in the field is:

A biomaterial is a nonviable material used in a medical device, intended to interact with biological systems.

Williams (1987).

A biomaterial is a nonviable material used in a medical device, intended to interact with biological systems.

Although biomaterials are most often applied to meet a therapeutic or diagnostic medical need, if the word medical is removed, this definition becomes broader and can encompass the wide range of applications already suggested. If the word nonviable is removed, the definition becomes even more general, and can address many new tissue-engineering and hybrid artificial organ applications where living cells are used.

Biomaterials science is the study (from the physical and/or biological perspective) of materials with special reference to their interaction with the biological environment. Traditionally, emphasis in the biomaterials field has been on synthesis, characterization, and the host–material interactions biology. Yet, most biomaterials (which meet the special criteria of biocompatibility—see Chapters 2.3.2 and 2.3.4) induce a nonspecific biological reaction that we refer to as the foreign-body reaction (Chapter 2.2.2). This leads us to consider a widely used definition of biocompatibility:

Biocompatibility is the ability of a material to perform with an appropriate host response in a specific application.

Williams (1987).

Biocompatibility is the ability of a material to perform with an appropriate host response in a specific application.

Examples of appropriate host responses include resistance to blood clotting, resistance to bacterial colonization, and normal, uncomplicated healing. Examples of specific applications include a hemodialysis membrane, a urinary catheter, or a hip joint replacement prosthesis. Note that the hemodialysis membrane might be in contact with the patient’s blood for 5   h (and outside the body), the catheter may be inserted for a week (inside the body, and designed to be easily removed), and the hip joint may be in place for the life of the patient (deeply implanted and meant to be long-term). This general concept of biocompatibility has been extended to tissue engineering, in which in vitro and in vivo processes are harnessed by careful selection of cells, materials, and metabolic and biomechanical conditions to regenerate functional tissues. Ideas central to biocompatibility are elaborated upon in Ratner (2011) and Chapter 2.3.2.

In the discussion of these definitions, we are introduced to considerations that set biomaterials apart from most materials explored in materials science. Table 1.1.1.1 lists a few applications for biomaterials in the body. It includes many classes of materials used as biomaterials. Note that metals, ceramics, polymers, glasses, carbons, and natural and composite materials are listed. Such materials are used as molded or machined parts, coatings, fibers, films, membranes, foams, fabrics, and particulates. Table 1.1.1.1 also gives estimates of the specific device global market size and, where available, an estimate of the number of medical devices utilized annually. The human impact, and the size of the commercial market for biomaterials and the broad array of medical devices, is impressive (Tables 1.1.1.1 and 1.1.1.2).

Table 1.1.1.1

Data compiled from multiple sources—these numbers should be considered rough estimates that are changing with growing markets and new technologies. Where only US numbers were available, world usage was estimated at approximately 2.5× US. B, Billion; M, million.

Table 1.1.1.2

Source: BCC Research.

The Expansion of the Biomaterials Field

Biomaterials research and development have been stimulated and guided by advances in cell and molecular biology, pathology, clinical medicine and dentistry, chemistry, materials science, and engineering. The biomaterials community has been the major contributor to the understanding of the interactions of materials with the physiological environment (often referred to as the biointerface). The development of biomaterials for medical and dental applications has evolved with time, as new concepts and understandings are applied to offer a broadening repertoire of choices to meet device design objectives (Fig. 1.1.1.2).

Early applications of biomaterials sought to achieve a suitable combination of functional properties to adequately meet the design needs for the medical device under development. Generally, this would involve the layering of biocompatibility concerns from host–material interactions on top of those more readily understood physical and chemical requirements. For instance, for a mechanical cardiac valve, materials could be selected and integrated to provide the functional response in an altering pressure flow field, resistance to cyclic mechanical wear, and suturability. In these early applications, industrial materials were typically taken off the shelf, i.e. medical grade biomaterials were not yet available. Nevertheless from the array of industrially available materials that might meet these requirements, considerations of blood and tissue compatibility would be included.

Pioneers in the device field effectively applied empirical approaches to arrive at materials that could meet both the traditional (nonbiological) design requirements and exhibit adequate levels of biocompatibility. Materials would generally be selected because they were tolerable (i.e., they elicited minimal response from the host tissues), and this would be consistent with biocompatibility for many applications (see Chapter 2.3.2). While the understanding of biomaterials science has evolved substantially from these early days, it is important to recognize that industrially repurposed materials continue to be utilized in many widely used medical devices today, including poly(tetrafluoroethylene) and poly(ethylene terephthalate), from which virtually all synthetic vascular grafts are made, stainless steel, cobalt–chromium alloys and titanium alloys, from which many orthopedic devices are constructed, and the polyurethanes and polysiloxanes that are utilized in a broad array of catheters and medical tubing. Furthermore, industrially adapted materials continue to be the biomaterials of choice for many revolutionary new devices introduced in recent years such as many of the components related to neurostimulatory devices and structural heart repair.

Figure 1.1.1.2 The growing palette of biomaterials. Generally moving with time from the 1940s adaptation of industrially available materials for early medical devices to the present, the breadth of described biomaterials continues to grow. In device development a biomaterial may be selected to leverage recent progress. However, it is important to note that major advances in the medical device field continue to be made with materials that could be considered first generation. The growing palette provides the design engineer with more tools to optimize device functionality in concert with other concerns such as manufacturability, regulatory burden, and economic considerations.

In this early period it would also occasionally be noted where an off-the-shelf material or class of materials might not fully achieve the target device design objectives and novel materials would be designed or refined specifically for a biomedical purpose. As highlighted in Chapter 1.1.2, biomaterials scientists would, for instance, create polyurethanes with segments selected for the purpose of improving blood biocompatibility. Hydrogels would be synthesized for soft tissue applications. Pyrolytic carbon, originally developed in the 1960s as a coating material for nuclear fuel particles, was studied and tuned for what is now in wide use in modified compositions to coat components of mechanical cardiac valves. These designed materials broadened the biomaterials palette, but the materials were still designed to be passive in achieving biocompatibility. As with early adapted industrial materials, these types of biomaterials continue to play an important part in device design and active research continues to seek to develop materials that are better suited for specific device applications while still targeting a passive, bioinert posture. For instance, efforts to find more degradation-resistant polymers for challenging device applications are ongoing (Chapter 2.4.2).

As knowledge of biological interactions with materials evolved, new types of biomaterials were developed with the intention of eliciting a controlled reaction with the tissues they contacted to induce a desired therapeutic effect. In the 1980s, these bioactive materials were in clinical use in orthopedic and dental surgeries as various compositions of bioactive glasses and ceramics (Hench and Pollak, 2002, Chapter 1.3.4), in controlled localized drug release applications such as the Norplant hormone-loaded contraceptive formulation (Meckstroth and Darney, 2001), and in the attachment of the anticoagulant heparin to the surfaces of membrane oxygenators with various modification strategies (Chapter 1.4.3B). Vascular stents have also been profoundly impacted by the implementation of a bioactive approach, with the application of polymer coatings that release antiproliferative agents and markedly reduce a major failure mechanism of tissue overgrowth and vessel occlusion (Chapter 2.5.2B).

Bioactive biomaterial development has also included the synthesis of resorbable polymeric biomaterials, with rates of degradation that could be tailored to the requirements of a desired application (Chapter 1.3.2F). Thus the discrete interface between the implant site and the host tissue could be eliminated in the long term, because the foreign material would ultimately be degraded to soluble, nontoxic products by the host. Many groups continue to develop new biodegradable polymers designed with defined objectives in strength, flexibility, a chemical composition conducive to tissue development, and a degradation rate consistent with the specific application. Degradable materials have been integral to the tissue-engineering paradigm where a scaffold, alone or in combination with cells and drugs, may provide for the generation of functional tissue. This paradigm as applied to the engineering of a cardiac valve is presented in Fig. 1.1.1.3 and is covered in the chapters of Section 2.6. Tissue-engineering approaches often leverage degradable biomaterials scaffolds, drug-releasing biomaterials, and in some cases utilize specific cell receptor–ligand interactions or enzymatic degradability to build bioactivity into the biomaterials scaffold (Chapters 1.4.4 and 1.4.5).

A characteristic of bioactive biomaterials development over the past several decades has been the leverage of fundamental knowledge from molecular biology. As this knowledge base has grown, biomaterials scientists and engineers have translated the understanding of biomolecular interactions to engineer biological interactions with designed materials. An early example of this was the application of knowledge of the adhesion peptide sequences from proteins such as fibronectin (e.g., Arg-Glu-Asp-Val) to engineer peptide-modified surfaces that would support specific types of cell adhesion (Hubbell et al., 1991). Polymeric materials with other novel properties such as shape-memory and programmable and interactive surfaces that control the cellular microenvironment are areas of development (Chapter 1.3.2G). In addition to having implications for medical applications, such engineered smart biomaterials systems have been used to advance our understanding of molecular biology principles, for instance, in elucidating the roles of substrate stiffness, ligand density, and three-dimensional culture in mammalian cell behavior.

The need for maximally effective pharmacologic dosing regimens and minimization of systemic toxicities has stimulated development of innovative particulate systems for targeted drug delivery and gene therapy (Chapter 1.3.8). Such systems may also provide the basis for targeted imaging or the combination of targeted imaging and therapeutic delivery, representing the growing field of theranostics. This focus area is experiencing a great deal of research attention at present by the biomaterials community and many of the approaches involve the production of nano- and microscale particulates using the principles of self-assembling materials. Several factors are driving this effort to design better biomaterials-based approaches: advances in protein and nucleic acid-based drugs (which cannot be taken in classical pill form, have high cost, and are labile); a better understanding of transport mechanisms systemically, within specific tissues or tumors, and intracellularly; and an increasing ability to create precise structures at macromolecular scales through controlled polymerization techniques and specific orthogonal reaction schemes.