I NTRODUCTION Biomaterials Science: A Multidisciplinary Endeavor Buddy D. Ratner, Allan S. Hoffman, Frederick J. Schoen, Jack Lemons or implants. Although this is a text on materials, it will quickly BIOMATERIALS AND BIOMATERIALS SCIENCE become apparent that the subject cannot be explored without also considering biomedical devices and the biological response Biomaterials Science: An Introduction to Materials in to them. Indeed, both the effect of the materials/device on the Medicine addresses the properties and applications of materials recipient and that of the host tissues on the device can lead to (synthetic and natural) that are used in contact with biologi- device failure. Furthermore, a biomaterial must always be con- cal systems. These materials are commonly called biomaterials. sidered in the context of its final fabricated, sterilized form. For Biomaterials, an exciting field with steady, strong growth example, when a polyurethane elastomer is cast from a solvent over its approximately half century of existence, encompasses onto a mold to form the pump bladder of a heart assist device, it aspects of medicine, biology, chemistry, and materials science. can elicit different blood reactions than when injection molding It sits on a foundation of engineering principles. There is also a is used to form the same device. A hemodialysis system serv- compelling human side to the therapeutic and diagnostic appli- ing as an artificial kidney requires materials that must function cation of biomaterials. This textbook aims to (1) introduce in contact with a patient’s blood and also exhibit appropriate these diverse elements, particularly focusing on their interrela- membrane permeability and mass transport characteristics. It tionships rather than differences and (2) systematize the subject also must employ mechanical and electronic systems to pump into a cohesive curriculum. blood and control flow rates. We title this textbook Biomaterials Science: An Intro- Because of space limitations and the materials focus of duction to Materials in Medicine to reflect, first, that the this work, many aspects of device design are not addressed book highlights the scientific and engineering fundamentals in this book. Consider the example of the hemodialysis sys- behind biomaterials and their applications, and second, that tem. The focus here is on membrane materials and their this volume contains sufficient background material to guide biocompatibility; there is little coverage of mass transport the reader to a fair appreciation of the field of biomaterials. through membranes, the burst strength of membranes, flow Furthermore, every chapter in this textbook can serve as a systems, and monitoring electronics. Other books and articles portal to an extensive contemporary literature. The magnitude cover these topics in detail. of the biomaterials endeavor, its interdisciplinary scope, and The words “biomaterial” and “biocompatibility” have examples of biomaterials applications will be revealed in this already been used in this introduction without formal defini- introductory chapter and throughout the book. tion. A few definitions and descriptions are in order and will Although biomaterials are primarily used for medical appli- be expanded upon in this and subsequent chapters. cations (the focus of this text), they are also used to grow cells A definition of “biomaterial” endorsed by a consensus of in culture, to assay for blood proteins in the clinical laboratory, experts in the field, is: in equipment for processing biomolecules for biotechnolog- ical applications, for implants to regulate fertility in cattle, A biomaterial is a nonviable material used in a medical device, in diagnostic gene arrays, in the aquaculture of oysters, and intended to interact with biological systems (Williams, 1987). for investigational cell-silicon “biochips.” How do we rec- oncile these diverse uses of materials into one field? The If the word “medical” is removed, this definition becomes common thread is the interaction between biological systems broader and can encompass the wide range of applications and synthetic or modified natural materials. suggested above. In medical applications, biomaterials are rarely used as iso- If the word “nonviable” is removed, the definition lated materials but are more commonly integrated into devices becomes even more general and can address many new nd Biomaterials Science, 2 Edition 1 Copyright © 2004 by Elsevier Inc. All rights reserved. [16:14 3/5/03 INTRD.tex] RATNER: Biomaterials Science Page: 1 2 INTRODUCTION—BIOMATERIALS SCIENCE: A MULTIDISCIPLINARY ENDEAVOR tissue-engineering and hybrid artificial organ applications TABLE 1 Some Applications of Synthetic Materials and where living cells are used. Modified Natural Materials in Medicine “Biomaterials science” is the physical and biological study of materials and their interaction with the biological envi- Application Types of materials ronment. Traditionally, the most intense development and investigation have been directed toward biomaterials synthe- Skeletal system sis, optimization, characterization, testing, and the biology of Joint replacements Titanium, Ti–Al–V alloy, stainless (hip, knee) steel, polyethylene host–material interactions. Most biomaterials introduce a non– Bone plate for fracture Stainless steel, cobalt–chromium specific, stereotyped biological reaction. Considerable current fixation alloy effort is directed toward the development of engineered sur- Bone cement Poly(methyl methacrylate) faces that could elicit rapid and highly precise reactions with Bony defect repair Hydroxylapatite cells and proteins, tailored to a specific application. Artificial tendon and Teflon, Dacron Indeed, a complementary definition essential for under- ligament standing the goal (i.e., specific end applications) of biomaterials Dental implant for tooth Titanium, Ti–Al–V alloy, stainless science is that of “biocompatibility.” fixation steel, polyethylene Titanium, alumina, calcium Biocompatibility is the ability of a material to perform with an phosphate appropriate host response in a specific application (Williams, 1987). Cardiovascular system Blood vessel prosthesis Dacron, Teflon, polyurethane Examples of “appropriate host responses” include the resis- Heart valve Reprocessed tissue, stainless steel, tance to blood clotting, resistance to bacterial colonization, and carbon normal, uncomplicated healing. Examples of specific applica- Catheter Silicone rubber, Teflon, tions include a hemodialysis membrane, a urinary catheter, or polyurethane a hip-joint replacement prosthesis. Note that the hemodialy- Organs sis membrane might be in contact with the patient’s blood for Artificial heart Polyurethane 3 hours, the catheter may be inserted for a week, and the hip Skin repair template Silicone–collagen composite joint may be in place for the life of the patient. Artificial kidney Cellulose, polyacrylonitrile (hemodialyzer) This general concept of biocompatilility has been extended Heart–lung machine Silicone rubber recently in the broad approach called “tissue engineering” in which in-vitro and in-vivo pathophysiological processes are Senses harnessed by careful selection of cells, materials, and metabolic Cochlear replacement Platinum electrodes Intraocular lens Poly(methyl methacrylate), silicone and biomechanical conditions to regenerate functional tissues. rubber, hydrogel Thus, in these definitions and discussion, we are introduced Contact lens Silicone-acrylate, hydrogel to considerations that set biomaterials apart from most materi- Corneal bandage Collagen, hydrogel als explored in materials science. Table 1 lists a few applications for synthetic materials in the body. It includes many materials that are often classified as “biomaterials.” Note that metals, ceramics, polymers, glasses, carbons, and composite materi- 80,000 replacement valves are implanted each year in the als are listed. Such materials are used as molded or machined United States because of acquired damage to the natural valve parts, coatings, fibers, films, foams and fabrics. Table 2 presents and congenital heart anomalies. There are many types of heart estimates of the numbers of medical devices containing bioma- valve prostheses and they are fabricated from carbons, met- terials that are implanted in humans each year and the size of als, elastomers, plastics, fabrics, and animal or human tissues the commercial market for biomaterials and medical devices. chemically pretreated to reduce their immunologic reactivity Five examples of applications of biomaterials now follow to and to enhance durability. Figure 1 shows a bileaflet tilting-disk illustrate important ideas. The specific devices discussed were mechanical heart valve, one of the most widely used designs. chosen because they are widely used in humans with good suc- Other types of heart valves are made of chemically treated pig cess. However, key problems with these biomaterial devices are valve or cow pericardial tissue. Generally, almost as soon as also highlighted. Each of these examples is discussed in detail the valve is implanted, cardiac function is restored to near nor- in later chapters. mal levels and the patient shows rapid improvement. In spite of the overall success seen with replacement heart valves, there are problems that may differ with different types of valves; they include induction of blood clots, degeneration of tissue, EXAMPLES OF BIOMATERIALS APPLICATIONS mechanical failure, and infection. Heart valve substitutes are discussed in Chapter 7.3. Heart Valve