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Biomaterials
Scott J. Hazelwood (Second Edition)
University of California, Davis

R. Bruce Martin (First Edition)

University of California, Davis

216.1 216.2 216.3 216.4 216.5 216.6 216.7 216.8

History Problems Associated with Implanted Devices Immunology and Biocompatibility Commonly Used Implant Materials Metals Polymers Ceramics Carbon Materials

The term biomaterials usually refers to human-made materials used to construct prosthetic or other medical devices for implantation in human beings. It can also refer to materials that otherwise come in contact with the tissues of internal organs (e.g., tubing to carry blood to and from a heart-lung machine). Despite advances in many areas of materials science, it would be a mistake to assume that modern technology has the ability to replace any part of a living organism with an articial material (or articial organ) that will be superior to the original structure. Although it is possible to imagine situations in which this might be true in some limited sense, the synthetic organism as a whole will rarely work better than when the original organ was in place. For example, a segment of bone may be replaced with a similar structure of titanium alloy having greater strength, but the metallic material will lack the ability of bone to adapt to its changing mechanical environment or repair fatigue damage over time.

216.1 History
The history of biomaterials can be divided into three eras. Prior to 1850, nonmetallic materials and common metals were used to fabricate simple prosthetic devices. Wood, ivory, iron, gold, silver, and copper were used to replace items such as teeth and noses, and to hold fractured bones together while they healed. In 1829, Levert experimented with lead, gold, silver, and platinum wire in dogs, but these metals clearly did not have the desired mechanical attributes. Furthermore, without anesthesia, patients could not endure long surgeries in order to implant signicant prostheses or xation devices. The second era of biomaterials, between 1850 and 1925, was dened by the rapid development of surgery as something other than an emergency procedure. The advent of anesthesia just before the mid19th century precipitated this development. In addition, x-rays were discovered by Roentgen and found immediate application in orthopedics in the late 1800s, revealing for the rst time the true nature of many skeletal problems. Finally, the acceptance of the aseptic surgical procedures propounded by Lister gradually but dramatically reduced the rate of postsurgical infections. The period from 1925 to the present is the third era, in which the primary advances in the various surgical specialties have resulted from three important developments. The rst was the development of cobalt chrome and stainless steel alloys in the 1930s and 1940s, respectively. The second was the

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development of polymer chemistry and plastics in the 1940s and 1950s. The third was the discovery of ways to produce useful quantities of penicillin and other antibiotics. The ability to further reduce surgical infection rates and to fabricate many devices that were compatible with biological tissues signicantly advanced the ability of surgeons to treat a great variety of problems. Most of the biomaterials commonly in use today were developed more than 30 years ago; the intervening years have been ones of gradual renement.

216.2 Problems Associated with Implanted Devices

There are many problems that a biomaterial should ideally overcome. It must be formable into the desired shape using economical methods and without compromising its mechanical properties. It must not corrode in the presence of body uids. This property entails the avoidance of crevice and fretting corrosion. A biomaterial must not poison the patient. It must either be free of toxic substances or those substances must be adequately locked into the structure of the material. Toxic ions that may be gradually released must not accumulate or lead to a long-term immunological response. A biomaterial must also be easy to sterilize (using steam under pressure, radiation, or ethylene oxide gas) without damaging its properties. The material must not break, either due to an occasional acute overload or due to fatigue from repeated functional loads. The strength and fatigue properties must combine with the shape of the implant to keep stresses within safe limits, particularly where stress concentrations cannot be avoided. Usually, the material must not simply work for a year or two, but for many years. A connective tissue implant must not perturb the stresses in adjacent tissues into a state that leads to atrophy of the tissues or prohibits normal repair of fatigue damage. Finally, implants must be made from materials that can be removed and replaced if they fail. Materials that are impervious to attack by the body may be difcult for the surgeon to remove as well.

216.3 Immunology and Biocompatibility

All organisms try to keep out foreign matter. If they fail in this, they work very hard either to destroy the invading object if its molecules look destructible or to isolate it through encapsulation in brous tissue if it looks impregnable. The problem of detecting foreign material is very complex, and the problem of overcoming an immune system that successfully copes with this task looms very large. In some cases, brous encapsulation does not have an adverse effect on an implant, but, as a general rule, biomaterials should be able to avoid the natural inclination of the body to either encapsulate them or break them down. Since doing this by destroying the natural defenses of the body (i.e., the immune system) is a poor tactic, the best way to proceed is to mask the foreign material from the chemical sensors of the host. This is difcult to do, since most materials will be easily recognized as outsiders and will not be able to avoid the consequences. One useful principle to remember is that materials with molecules that look like biological molecules will be more readily attacked by destructive cells. For example, nylon and polyethylene both have a core of carbon atoms with hydrogens attached along their lengths. The main difference between the two is that polyethylene has a CH3 terminal group, whereas nylon has an NH2 terminal group. Since proteins have the latter kind of terminus, nylon tends to be more susceptible than polyethylene to degradation by cells of the immune system. On the other hand, it may be very difcult to induce the body to attach tissue to impregnable materials such as polyethylene. In fact, no polymers have been found that are both immune to degradation and amenable to tissue adhesion. Some materials, though, are very attractive to connective tissue cells. For example, hydroxyapatite is nearly identical to bone mineral, and will quickly become integrated with bone when implanted in the skeleton. Unfortunately, hydroxyapatite is not nearly as tough and strong as bone. The commonly used materials that are tough and strong metals cannot be destroyed by the immune system, so the body tends to encapsulate them in brous tissue. This makes it difcult to rigidly attach them to bone.

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TABLE 216.1 Mechanical Properties of Metals and Ceramics Commonly Used in Biomedical Implantsa
Material Stainless steel Cast cobalt-Cr Wrought cobalt-Cr Ti-6Al-4V alloy Pure titanium Al2O3b ZrO2c Apatite C-Si composite
a

Elastic Modulus (GPa) 193 235 235 117 100 380 210 62 21

Maximum Strain (%) 10 8 12 10 15 0 0 0 0

Tensile Strength (MPa) 1000 670 1170 900 410 50 690 690

Values are approximations compiled from the references listed at the end of this chapter. Given the variability in manufacturing processes, precise values cannot be given for mechanical properties. b Compressive strength = 4 GPa. c Compressive strength = 3 GPa.

TABLE 216.2 Mechanical Properties of Polymers Commonly Used in Biomedical Implantsa

Material Silicone rubberb Polyether urethane PTFE UHMWPE PMMA
a

Elastic Modulus (MPa) 2.4 0.4 500 2000

Maximum Strain (%) 700 700 300 350 2

Tensile Strength (MPa) 41 30 35 30c

Values are approximations compiled from the references listed at the end of this chapter. Given the variability in manufacturing processes, precise values cannot be given for mechanical properties. b Modulus at 100% strain. c Compressive strength = 90 MPa.

216.4 Commonly Used Implant Materials

Human-made biomaterials may be broadly categorized into metals, polymers, ceramics, and carbon composites. The materials in each of these categories may contain several forms, such as solids, membranes, bers, or coatings. They may also serve many purposes, including replacing structural organs or organs that carry out chemical exchanges, housing electronic devices, repairing damaged or congenitally defective cardiovascular or connective tissue, or delivering drugs. Tables 216.1 and 216.2 show mechanical properties of metals and polymers commonly used as biomaterials. Table 216.3 shows the properties of some connective tissues that these materials are designed to replace.
TABLE 216.3 Mechanical Properties of Major Connective Tissuesa
Material Bone Cartilage (costal) Collagen (tendon) Keratinb
a

Elastic Modulus (MPa) 20,000 14 1300 5000

Extensibility (%) 1.5 8.0 9.0 2.0

Tensile Strength (MPa) 150 1 75 50

Values are approximations compiled from the references listed at the end of this chapter. Given the variability of biological tissues, precise values cannot be given for mechanical properties. b For the alpha-form region of tensile tests of wool.

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TABLE 216.4 Approximate Compositions of Common Biomaterial Alloysa

Alloy Cobalt-chrome Stainless steel Titanium
a

Approximate Composition 60% Co, 28% Cr, 6% Mo, 3% Ni, 3% other (Fe, C, Mn, Si) 62% Fe, 18% Cr, 14% Ni, 3% Mo, 0.03% C, 3% other (Mn, P, S, Si) 90% Ti, 6% Al, 4% V, 0.4% other (Fe, C, O)

Values are approximations compiled from the references listed at the end of this chapter.

216.5 Metals
Cobalt-chromium alloys were the rst corrosion-resistant alloys to be developed and have proven very effective in surgical implants, beginning in 1936 when Venable reported the use of such a material in orthopedics. Most alloys of this material are primarily cobalt. Chromium is added to provide resistance to corrosion. They are usually regarded as the metal of choice in skeletal prostheses. They have historically been available in cast and wrought forms. As with stainless steel, the wrought material is substantially stronger. The mechanical properties and composition of each alloy discussed in this section are shown in Tables 216.1 and 216.4, respectively. Modications of Co-Cr alloys contain less cobalt and chromium and larger amounts of other alloy materials (35% nickel in one case and 15% tungsten in another). They can be forged and heat treated to obtain tensile strengths signicantly above those of stainless steel and the more common Co-Cr alloys as high as 1800 MPa. Stainless steel (usually 316L) is a common industrial alloy that has been very successful as a surgical implant material. Both stainless steel and cobalt-chrome alloys owe their corrosion resistance to the formation of a passive ceramic-like CrO2 coating on the surface, and it is important that this coating not be scratched during implantation. Care must be taken with stainless steel materials in orthopedic applications because of their susceptibility to crevice and stress corrosion. The ductility of these alloys can be increased by heat treatment, and their strength can be increased by cold working of the material. Cast stainless steels are unsuitable for use in weight-bearing situations because of their large grain sizes and low fatigue strengths. Type 316LVM (low carbon [L, typically less than 0.03%], vacuum melt [VM]) material is preferred. The carbon concentration must remain at small amounts in stainless steel materials to maintain resistance to corrosion. Titanium alloys are primarily Ti-6Al-4V (i.e., 6% aluminum, 4% vanadium, and 90% titanium). Pure titanium is also used, primarily in dental applications. As with cobalt-chrome alloys and stainless steel, titanium and its alloys offer excellent biocompatibility and corrosion resistance. In fact, the titanium oxide (TiO2) passive layer formed on the surface of these alloys increases the resistance to corrosion compared to that of the other implant metals. Titanium alloys are becoming increasingly popular in orthopedics because their strength is as good as the other metal implant materials, but they are only half as stiff (Table 216.1). This is potentially important because a large elastic modulus mismatch between implant and bone causes stress concentrations in some places and tends to stress shield the bone in others. However, the modulus of titanium alloys is still several times greater than that of bone (Tables 216.1 and 216.3), and marked decreases in stress shielding when these alloys are used have not yet been demonstrated. Titanium alloys are also sensitive to notching. A notch or scratch on titanium alloy implants will signicantly reduce their fatigue life.

216.6 Polymers
Polymethylmethacrylate (PMMA) is an acrylic plastic from which parts may be machined. It also may be polymerized in the body to x a hip prosthesis stem into the medullary canal or ll a bony defect. Frequently, this polymer will have an additive: (1) barium to increase its radiographic visualization, or (2) an antibiotic to prevent infection following surgery. The mechanical properties of PMMA are shown
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in Table 216.2; barium and antibiotic additions do not substantially affect these properties. Typically, PMMA used for orthopedic applications to x implants is prepared by vacuum or centrifuge mixing systems that reduce the void space in the polymerized form. Treatment of the PMMA in this way increases its ultimate strength compared to that which is mixed by hand. PMMA polymerizes with an exothermic reaction that causes the doughy mass used in hip surgery to reach temperatures in the vicinity of 40C, although laboratory reports indicate temperatures of 60C to 90C may be achieved depending on the amount of cement. In addition, PMMA has the effect of causing blood pressure to drop momentarily when it is implanted during hip surgery. PMMA is also used in the manufacture of hard contact lenses and of intraocular lenses for cataract patients. For this application, polymerization is initiated with heat to produce an extremely clear material with good optical properties. Soft contact lenses are usually hydrogels made of homo- or co-polymers of hydroxyethyl methacrylate; other methacrylates and silicones have also been used, however. Ultra-high molecular-weight polyethylene (UHMWPE) has a very simple chemical structure, consisting of chains of carbon atoms with hydrogen atoms attached to the sides. In the ultra-high molecular-weight form, these chains achieve a molecular weight of 1 to 4 million. Sterilization of UHMWPE components used as bearing surfaces against one of the metal alloys is mainly accomplished through gamma irradiation, which oxidizes polyethylene and may negatively affect the wear properties of the material. Conducting the sterilization procedure in an environment free of oxygen signicantly reduces the wear rate of UHMWPE by inducing cross-linking between polymer chains. Polyethylene has also been used to replace the ossicles of the inner ear. Polydimethylsiloxane (silicone rubber) is a widely used polymer that was rst applied biomedically in a hydrocephalus shunt in 1955. It has a long history of biological compatibility and clinical testing in a great variety of applications, and a medical grade (Silastic) has been developed with superior biocompatibility and mechanical properties. It can be sterilized by steam, radiation, or ethylene oxide. This polymer can be manufactured with various degrees of cross-linking to adapt its mechanical properties for other purposes as well. Silicone rubber is commonly used for catheters. Rubbery sheets of silicone have been used in hernia repair, and a gel silicone often has been used for breast prostheses or augmentation. (The recent controversy over the safety of the latter application is a good example of the difculty in assessing the biocompatibility of biomaterials. Different individuals may respond quite differently to the same material.) Harder versions have served as balls in ball-and-cage heart valves. Silicone rubber is widely used in pacemakers and biomedical research to form seals against body uids for electrical leads. It is used as the functional membrane in both kidney dialysis and extracorporeal blood oxygenator machines. It also has been used in drug delivery implants, where it serves as a membrane through which the drug slowly passes. Silicone also serves as a structural material in prosthetic heart valves and to replace the auricle or the ossicles of the ear. In orthopedics, silicone rubber is formed into soft, exible strap hinges for the replacement of arthritic nger, wrist, or toe joints. However, its fatigue resistance is not as good as it should be for this application. Dacron has been used for blood vessel prostheses since the pioneering work of DeBakey in 1951. Dacron is thrombogenic, so the pores in the fabric soon become lled with coagulated blood, which is then replaced by a tissue called neointima that serves as a biological wall between the Dacron and the blood. However, if the vessel diameter is smaller than 6 mm, the neointima will prevent blood ow in the tube. Dacron has also been used in prosthetic heart valves. Polytetrauoroethylene (PTFE, Teon, or Gore-Tex) has been used to produce blood vessel prostheses smaller than 6 mm in diameter, and the neointima appears to be thinner with this material. However, it too is unsatisfactory for most human blood vessels that are smaller than 3 mm. PTFE is also used to make prosthetic heart valves, ligaments, shunt tips, and articial ossicles for the ear. Polyether urethane has been used for years in blood bags and tubing for kidney dialysis machines. It has also been tried as a material for blood vessel replacement. It is frequently found in intra-aortic balloon pumps and in articial hearts, where it lines the chambers and forms the pumping diaphragm. The primary requirement in the latter application is fatigue resistance; a prosthesis that is to last 10 years must ex about 360 million times. Materials that reportedly have been tried for this purpose and found
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to have insufcient fatigue properties include several other polymers used in tubing for kidney dialysis machines: polyvinylchloride, silicone rubber, and natural and synthetic rubbers. Polyalkylsulfones are used in blood oxygenator membranes. Hexsyn is a brand name of a recently developed elastomer that has good biological compatibility and an extraordinarily high fatigue life (more than 300 million cycles to failure, compared to 600,000 for silicone rubber in an ASTM D430 exure test). It has been used for heart valves and human nger-joint prostheses. Epoxy resins have been used to encapsulate electronic implants and with carbon ber reinforcement for dental implant posts. Polydepsipeptides, polylactic acid, polyglycolic acid, polydioxanone, and polycaprolactone polymers have been used with some success as biodegradable implants. Implant materials that disintegrate gradually in body uids are useful as sutures, screws, pins, bone plates, to ll defects in bone or other tissues, and for the delivery of embedded drugs.

216.7 Ceramics
Ceramics generally have hydrophilic surfaces amenable to intimate bonding with tissues. They are very biocompatible but brittle relative to biological materials, including bone. One of their primary applications is as a coating (optimally 25 to 30 micrometers thick) for metals to promote attachment to bone. Hydroxyapatite [Ca10(PO4)6(OH)2] and tricalcium phosphate [TCP, Ca3(PO4)2] in various forms have proven to be very biocompatible and form intimate bonds with bone. Unfortunately, their tensile strengths are not great. They also may be made in porous or granular forms and used to ll bone defects in lieu of a bone graft. TCP may eventually be resorbed and replaced by bone; hydroxyapatite is less resorbable. Alumina, a polycrystalline form of Al2O3, is a widely used industrial ceramic. It has relatively good strength and excellent wear-resistance characteristics, but is very stiff and brittle compared to bone. It is sintered from alumina powder under pressure at 1600C to form structures with relatively smooth surfaces. A principal use of this material is to form the heads of total hip prostheses. Alumina has also been used in dental implants, as corneal replacements, and as substitutes for bones in the middle ear. Zirconia (ZrO2) is also used in bearing surfaces as the head of femoral joint implants. As with alumina, zirconia has good strength and wear-resistance properties. Because of its low modulus and high strength, zirconia femoral heads can be manufactured into a wide range of diameters and lengths for joint replacement applications. Bioglass (Na2O-CaO-P2O5-SiO2) is a glass with soluble additives designed to form a silica gel at its surface and thereby aid chemical bonding to bone. Bioglass implants have been used in many dental applications and may be used to replace several bones in the ear.

216.8 Carbon Materials

Graphite has a weak, anisotropic crystalline structure, but isostatic (or turbostratic) carbon is isotropic and relatively strong. The two most useful forms of turbostratic carbon in biomedical applications are vitreous (or glassy) carbon and pyrolytic low-temperature isotropic (LTI) carbon. These are both isotropic materials, but the latter is more wear resistant and stronger. Turbostratic carbons, carbon-ber PMMA, and carbon-silicon composites have excellent biocompatibility and can have elastic moduli similar to bone. However, it typically turns out that in order to reduce the stiffness of these materials to match that of bone, the strength must be reduced to less than that available in metals. In the last decade, a number of these materials have been tested for various biomedical applications, but few have been widely used. Carbon-silicon and carbon-coated graphite, however, have been used in heart valves, and pyrolytic carbon coating has been shown to improve bone growth into porous metal surfaces.

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Dening Terms
Biocompatibility The ability to remain in direct contact with the tissues of a living person without signicantly affecting those tissues, or being affected by them, other than in a prescribed way. For example, a biocompatible material used in a blood vessel wall would contain the blood under pressure but would not adversely interact with its constituents or other adjacent tissues. Biomaterial An engineering material suitable for use in situations where it may come into direct contact with internal tissues of the body. Usually, this means in a surgically implanted device, but it may also include devices that contain or process blood, or other uids, that will be returned to the body. Sometimes, biomaterial is used to refer to a biological structural material. Connective tissue Tissue that primarily serves a mechanical rather than a metabolic or chemical function. The volume of the cells in such tissue is small relative to the extracellular components. For example, tendons are composed primarily of extracellular collagen, with a small fraction of their volume occupied by the cells that produce the collagen. Fibrous encapsulation The formation of connective tissues around a foreign object in order to isolate it from the rest of the body, both physically and chemically. Stress shield To reduce the stress in a region of bone by placing it in parallel with an implant that is stiffer. Bone is able to adjust its structure to the applied loads, and if the imposed load is reduced, the affected bone will atrophy. This may leave the prosthesis inadequately supported and lead to failure.

References
Budinski, K. G. and Budinski, M. K., Engineering Materials: Properties and Selection. Prentice Hall, Upper Saddle River, NJ, 1999. Gebelein, C. G., Polymeric Materials and Articial Organs. American Chemical Society, Washington, DC, 1984. Hastings, G. W. and Ducheyne, P., Natural and Living Biomaterials. CRC Press, Boca Raton, FL, 1984. Hench, L. L. and Ethridge, E. C., Biomaterials: An Interfacial Approach. Academic Press, New York, 1982. Kossowsky, R. and Kossovsky, N., Materials Sciences and Implant Orthopaedic Surgery. Martinus Nijhoff, Boston, MA, 1986. Lin, O. C. C. and Chao, E. Y. S., Perspectives on biomaterials. Proceedings of the 1985 International Symposium on Biomaterials. Taipei, Taiwan, 2527 February 1985. Elsevier, Amsterdam, 1985. Nahum, A. M. and Melvin, J., The Biomechanics of Trauma. Appleton-Century-Crofts, Norwalk, CT, 1985. National Research Council. Internal Structural Prostheses: Report of a Workshop on Fundamental Studies for Internal Structural Prostheses. National Academy of Sciences, Washington, DC. Ratner, B. D., et al. Biomaterials Science: An Introduction to Materials in Medicine. Academic Press, San Diego, CA, 1996. Shackelford, J. F., Bioceramics. Gordan and Breach Science, Australia, 1999. Tsuruta, T., et al. Biomedical Applications of Polymeric Materials. CRC Press, Boca Raton, FL, 1993. Wright, T. M. and Li, S., Biomaterials. In: Orthopaedic Basic Science, 2nd ed., Buckwalter, J. A., Einhorn, T. A., and Simon, S. R., Eds. American Academy of Orthopaedic Surgeons, Rosemont, IL, 2000.

Further Information
Black, J., Orthopaedic Biomaterials in Research and Practice. Churchill Livingstone, London, 1988. Kambik, H. E. and Toshimitsu, A., Biomaterials Mechanical Properties. ASTM International, Philadelphia, PA, 1994. Szycher, M., Biocompatible Polymers, Metals, and Composites. Technomic, Lancaster, PA, 1983. Szycher, M., High Performance Biomaterials: A Comprehensive Guide to Medical and Pharmaceutical Applications. Technomic, Lancaster, PA, 1991.

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Szycher, M., Szychers Dictionary of Biomaterials and Medical Devices. Technomic, Lancaster, PA, 1992. Von Recum, A. F., Handbook of Biomaterials Evaluation: Scientic, Technical, and Clinical Testing of Implant Material. Taylor & Francis, Philadelphia, PA, 1999.

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