02 Classes of Materials - Chapter - Mow - Huiskes Book

A. El-Ghannam, P. Ducheyne Biomaterials In: Basic Orthopaedic Biomechanics and Mechanobiology Eds., Van C.
Mow and Rik Huiskes, Lippincott-Williams and Wilkens, 2005
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BIOMATERIALS
AHMED EL-GHANNAM PAUL DUCHEYNE
1 2
THE MATERIALS SCIENCE TRIAD 00 CLASSES OF MATERIALS 00
6 METALLIC BIOMATERIALS CORROSION RESISTANCE AND RELATED PROPERTIES 00 7 BONE BIOACTIVE CERAMICS 00
2.1 2.2 2.3 2.3

3
Metals 00 Ceramics 00 Polymers 00 Composites 00

CRYSTAL STRUCTURE 00
3.1 3.2
4
Metals and Ceramics 00 Polymers 00

MECHANICAL BEHAVIOR 00
7.1 Calcium PhosphatesStructure, Mechanical Properties, and Processing 00 7.2 Calcium PhosphatesBiological Behavior 00 7.3 Calcium PhosphatesCoatings 00 7.4 Bioactive Glasses 00 7.5 Bioactive Glass Ceramics 00
8 TISSUE ENGINEERING AND RECENT DEVELOPMENTS 00
4.1 4.2 4.3

5
Mechanical Properties 00 Fracture Mechanics of Ceramics 00 Elastic Properties of Composites 00

WEAR RESISTANCE 00
8.1 8.2
Bone Tissue Engineering 00 Engineering Surfaces with Peptides 00
5.1 Ultrahigh-molecular-weight Polyethylene 00 5.2 Alumina 00
1 THE MATERIALS SCIENCE TRIAD Biomaterials including ceramics, metals, and polymers have been widely used in surgery. Some biomaterials with relatively high mechanical strength such as the titanium alloy Ti-6Al-4V, the Co-Cr alloys, alumina, or zirconia have been used in joint replacement devices. Others with bioactivity and bone bonding ability such as calcium phosphate ceramics and bioactive glasses have been used as articial bone grafts. The principle that is of most value with respect to assessing properties of a material originates from the internal structure of that material. At an ultramicroscopic and light microscopic level, materials are made up of atoms which
are associated with their neighbors in crystals, molecules, multiphase arrangements, and microstructures. In this chapter we shall focus extensively on structures and how they affect the behavior of the biomaterial. Biomaterials must be processed to meet the requirements of a specic biological application. The most familiar processing steps simply change the shape of the materials by machining or forging. However, processing commonly involves more than simply changing the shape of the material. For example, thermal processing is required to coat metallic implants with a calcium phosphate surface intended to enhance xation and hence longevity of the implant. During coating the internal structure of the material may be
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altered, in its turn resulting in a change of biological properties. It is obvious then that the processing-induced structural changes must be understood, lest it be impossible to formulate appropriate processing steps. The relationship among structure, properties, and processing is called the materials science triad. This concept is all-important in biomaterial science, no matter which material is considered. Thus in this chapter we will always indicate properties as a function of structure and processing. 2 CLASSES OF MATERIALS As is the case for materials, biomaterials can be conveniently grouped into three classes: metals, polymers, and ceramics. This scheme is based primarily on the chemical makeup and atomic structure of the various materials. Composites, representing another group of materials, consist of combinations of two or more metals, polymers, or ceramics. An alternative classication scheme relates to the biological properties of biomaterials, including bioinert or bioactive. In this chapter we do not use this method to organize material classes. 2.1 Metals Metal atoms are held together in a crystal lattice by the interaction of the valence electrons (outermost electrons) with the positive metallic ions. These nonlocalized electrons are free to move throughout the solid, because the valence electrons are not tightly bound to the metal ions. Such an arrangement is called the metallic bond. This distinguishes it from the covalent and ionic bonds present in polymers and ceramics, respectively. In these other congurations, electrons are not free to roam (Fig. 11-1). In what follows, some illustrations of the importance of the type of bond vis-`-vis biomaterials behavior are given. a The independent electrons in the metallic bonds can quickly transfer electric charge and thermal energy. As a result of the different binding states of the electrons, there is a difference in thermal expansion coefcient between metAu: Do you
FIGURE 11-1. Schematic representation of cova- have written lent, metallic, and ionic bonding.
Fig.11.1
als and ceramics. Since it is often desirable to coat metallic implants with a bioactive ceramic lm in order to improve implant xation, the difference in thermal properties between metals and ceramics is an important issue, as this difference may be at the basis of destabilization of the coating. Specically, the difference in the thermal expansion coefcient between metals and ceramics results in interfacial shear stresses that can create microcracks at the interface during cooling subsequent to plasma-spraying a calcium phosphate coating onto a metallic implant. After implantation, preferential degradation of the ceramic at the ceramicmetal interface can result in removal of the coating layer and hence, poor xation. As the electrons can move easily in metals, neighboring atoms are weakly bonded, making metals easily deformable. This facilitates wear, except if special processing techniques are employed with the intent to enhance bonding in the metallic structure. Wear of a metallic implant can result from micromotion and friction in the implantation bed against a counterpart that has the same or higher hardness. Accumulation of wear debris has been related to aseptic loosening and implant failure. As the number of valence electrons increases down the periodic table, they become more
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localized and the metallic bonds become more directional, resulting in more brittle metals. This property is also related to the high melting temperature of such brittle metals as tungsten. As the mechanical properties (and also the chemical and physical properties) of metals can be improved by alloying, most metals used in orthopedic surgery are alloyed. Obvious examples are the alloys based either on titanium or on cobalt. 2.2 Ceramics Ceramics are composed of compounds made of metallic and nonmetallic elements. With nonmetallic elements typically oxygen, nitrogen, or carbon, ceramics are frequently oxides, nitrides, or carbides. Ceramic biomaterials include calcium phosphate ceramics, bioactive glasses, bioactive glass ceramics, alumina, and zirconia. Each of these materials is relatively hard and brittle. In fact, hardness and brittleness are typical properties of ceramics, as are excellent resistance to high temperatures and corrosive environments. The basis of these characteristics is again related to the type of atomic bonds. The metallic elements release their outermost electrons to the nonmetallic atoms. This directional bond produces electrons that are localized in the structure. Thus, typical ceramic materials are good insulators, both electrically and thermally. Considerable energy is usually required to separate the atoms that have lost electrons (cations) from the atoms that have gained electrons (anions). As a corollary, wear is low with ceramic implant materials. Glasses and carbon materials are commonly regarded as ceramic materials, as they are com-
posed of ionically bonded components and display the characteristic properties of ceramics, such as great hardness, lack of permanent deformability, and excellent chemical inertness. These materials, however, do not have the longrange order typical of crystalline materials. Their atomic arrangement is one of short order. Bioactive glass is a family of glass compositions with the ability to bond to bone and enhance bone tissue formation. Collectively, bone bonding and bone tissue growth enhancement are termed bone bioactive behavior. Bioactive glasses are composed of silicon oxide, which is the network former in the glass structure, and calcium oxide and sodium oxide which are the network modiers. Figure 11-2 shows the schematic struc- Fig.11.2 ture of a random glass network composed of a network former (SiO2 ) and network modiers (Na2 O and CaO). Some of the Si are bonded to each other by bridging oxygen bonds and others are coordinated with nonbridging oxygen bonds to network modifying ions in SiO2 -Na2 O-CaO glass. Other additives such as phosphorus pentoxide (P2 O5 ) can be added to modulate bone bioactivity reactions. With decreasing SiO2 concentration, the instability and, hence, the bioactivity of the bioactive glasses increase. Bioactive glass granules with a SiO2 concentration as low as 45% by weight can be used as a resorbable bone graft material. 2.3 Polymers Unlike metals, which have migrant electrons, the nonmetallic atoms of polymers are covalently bonded. That is, elements such as C, N, and O have an afnity for attracting or sharing
FIGURE 11-2. Schematic structure of a random glass network composed of a network former (SiO2 ) and network modiers (Na2 O and CaO).
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collagen. This makes it possible to incorporate other substances by direct bonding. An example is a heparin coating on polymer surfaces in an effort to prevent blood clotting. During polymer processing additives such as antioxidants, antidiscoloring agents, and plasticizers are added to facilitate the polymerization reaction and enhance processability. Some of these additives are toxic; therefore, pure medical-grade polymers are not readily available, except in very limited cases. 2.4 Composites Composite materials are solids that contain two or more distinct constituent materials or phases, on a scale larger than the atomic. The term composite is usually reserved for those materials in which the distinct phases are separated on a scale larger than the atomic and in which properties such as the elastic modulus are signicantly altered in comparison to those of a homogenous material. Accordingly, reinforced plastics such as berglass as well as bone are viewed as composite materials, but alloys are not. The properties of a composite material depend on the shape, volume fraction, and interface between the constituent phases. The shape of the phases in a composite material is classied into three categories as shown in Fig. 11-4. Most composite biomate- Fig.11.4 rials have been developed to enhance mechanical and biocompatibility behavior. The strength of composites derives in part from the fact that ne bers or whiskers of a material can be made nearly defect free for greatly increased strength, as is shown in Table 11-1. Carbon bers have tab.11.1 been incorporated in high-density polyethylene tibial plateaus of total knee replacements. Although strength was greatly enhanced, wear behavior was fully unsatisfactory.
FIGURE 11-3. Various polymer chains. (From Park JB. Biomaterials science and engineering. New York: Plenum Press, 1984.)
Fig.11.3
additional electrons. Thus, in covalently bonded elements, each electron is associated with a pair of atoms. Materials that contain only nonmetallic elements share electrons to build up large molecules, often called macromolecules. These large molecules contain many repeating units, or mers, from which comes the word polymers. The polymeric molecular arrangements can be linear, branched, or cross-linked (Fig. 11-3). The simplest example is polyethylene, which is derived from ethylene (CH2 = CH2 ), in which the carbon atoms share electrons with two other hydrogen and carbon atoms CH2 (CH2 CH2 )n CH2 , where n indicates the number of repeat units. To make a strong solid, n should be well over 10,000, making the molecular weight of the polymer more than 1 million grams/mole. Polymers bear a close resemblance to natural tissue components such as
(A)
(B)
(C)
FIGURE 11-4. Morphology of basic composite inclusions: (A) platelet; (B) ber; (C) particle.
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TABLE 11-1. PROPERTIES OF FIBERS USED FOR COMPOSITE MATERIALS
Class Whisker Material Graphite Al2 O3 Iron Si3 N4 SiC Boron Asbestos Drawn silica Boron glass High-tenacity nylon 66 Carbon steel Molybdenum Tungsten Tensile Strength (GPa) 20.7 15.2 12.4 13.8 20.7 5.9 5.9 2.4 0.8 3.9 2.1 2.9
Youngs Modulus (GPa) 675.7 524.0 193.1 379.2 689.5 441.3 186.2 72.4 379.2 4.8 206.9 365.4 344.8
Glass, ceramic
Polymer bers Metal wire
3 CRYSTAL STRUCTURE 3.1 Metals and Ceramics Analyzing the atomic arrangements within a solid considerably facilitates studying the effect of bond type on resulting material properties. All metals, most ceramics, and some polymers crystallize when they solidify. A crystalline material is characterized by long-range order and an innitely repeating unit cell of atoms/ions. For example, metals can have their atoms arranged in an orderly three-dimensional lattice, of which a two-dimensional section is shown in Fig. 11-5. In this two-dimensional lattice any square can be repeated by moving one lattice spacing a in any direction. If this is extended into three dimensions, the spatial structure so dened is a simple cube, and the crystal structure is called a cubic crystal system. The unit cell is the smallest three-dimensional structure that can be repeated within the lattice. The unit cell
Fig.11.5
FIGURE 11-5. Two-dimensional section of a simple cubic lattice structure (a, lattice space).
of stainless steel is a cube with atoms located at the corners and middle of each side. This crystal structure is called a face-centered cubic (FCC) crystal. A cubic crystal with atoms located at corners and in the center of the cube is called a body-centered cubic crystals lattice (BCC). In addition to a cubic structure, there are six other structures (Fig. 11-6). Apart from the Fig.11.6 face-centered location of atoms, several other so-called space lattices are possible; we indicate these only as they specically relate to the biomaterials analysis. Figure 11-7 shows the arrange- Fig.11.7 ments of the atoms in an FCC and a hexagonal structure, specically the hexagonal closepacked (HCP) structure. As this gure shows, these two lattice systems have the closest packing of atoms. In the FCC structure, the plane of closest packing runs through the three corners indicated by 1, 1 , and 1 . Neighboring planes run through corners 2 or 3. Closest-packed planes of the HCP lattice are parallel with the base of the hexagonal prism. It is apparent that there is considerable congurational symmetry in these structures. This allows deformation of the structure in a great variety of ways. Thus, since the cubic and hexagonal lattices are very common metal lattices, it further substantiates the easy deformability of metals. The crystal structures, at room temperature, of some of the materials used in hip surgery are summarized in tab.11.2 Table 11-2. Figure 11-8 shows the HCP structure of hy- Fig.11.8 droxyapatite (HA), a bone bioactive ceramic.
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FIGURE 11-6. Geometric representation of the seven atomic lattices.
Comparison of the titanium HCP structure with this structure reveals that the HA structure is considerably more complex, as a result of which, displacement of atoms within the lattice is difcult. Thus the structure is resistant to deformation and, when overloaded, fractures rather than deforming permanently. 3.2 Polymers Polymers are the result of chain reactions that give rise to linear, branched, or cross-linked polymeric molecular arrangements (Fig. 11-3). As the extent of polymerization increases and the molecular chains become longer, the relative mobility of the chains in the structure decreases (Fig. 11-9). As a result, alignment of the chains and formation of long-range order, i.e., crystallinity, is difcult. Polymers such as polyethylene and polyamide cannot be crystallized easily, because the individual chains are long. Alignment is further rendered difcult by the
Fig.11.9
variability of the chain length. As the chain ends act as defects, this repeatedly interrupts the regular continuity in the structure. Nevertheless, under optimal conditions, some crystallization is possible: Various multimolecular structures are Fig.11.10 shown in Fig. 11-10. The chain mobility, which is directly proportional to the molecular weight, is related not only to crystallinity, but also to mechanical strength. Thus, the molecular and microstructural arrangements have a profound inuence on resulting properties. Factors affecting the strength of polymers further include chemical composition, side groups, cross-linking, copolymerization, and blending. By way of example we can consider the very strong aromatic polyamid bers, better known by their trade name Kevlar. These bers are made up of highly directional molecular chains, which confer on the bers great strength. This structure, however, cannot be obtained in thick sections. Thus, in order to make optimal use of the excellent strength, these
FIGURE 11-7. FCC and HCP crystal lattices.
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TABLE 11-2. SOME MATERIALS AND THEIR REPRESENTATIVE EQUILIBRIUM CRYSTAL STRUCTURE AT BODY TEMPERATURE
Material Cobaltchromium alloy Stainless steel AISI 316L Titanium (Ti) Titanium alloy (Ti-6Al-4V annealed) Tantalum (Ta) Niobium (Nb) Gold (Au) Alumina (Al2 O3 ) Hydroxyapatite [Ca10 (PO4 )6 (OH)2 ] FCC FCC HCP Two-phase material: HCP BCC BCC BCC FCC HCP HCP Structure
The units of (N/m2 = Pa) show that stress and pressure are similar concepts. Under this force, there also will be a strain, , due to change from the original length. = l /l 0 (2)
At low stress and low strain, stress is proportional to strain, i.e., = E (3)
bers are usually embedded in a matrix, i.e., used in composites. 4 MECHANICAL BEHAVIOR 4.1 Mechanical Properties Mechanical properties including elasticity and strength are important properties to consider in the selection of a material for a specic implant design. In this section we describe the various mechanical properties relevant to biomaterials. Many of the mechanical properties of a material take into account how it behaves under load. If a load, F, is applied to a material of cross section A, it is subjected to a stress, , = F/A (1)
E is constant for a material at low . It is called Youngs modulus or modulus of elasticity of the material. E is a measure of stiffness (i.e., resistance to strain) of a material, and is quite distinct from strength. A small value of E means that a small stress gives a large extension (as in rubber); a large value of E indicates that the material is very stiff (as in diamond). The E values are 7 MPa and 1.2 106 MPa for rubber and diamond, respectively. Whereas equation 3 describes the mechanical behavior of a material at low stress, a more extensive graphical representation of materials deformation is given in Fig. 11-11. This gure Fig.11.1 shows the proportionality of stress to strain at low stress, as well as the deviation from linearity at higher stress. The stress at which elongation is no longer reversible is called the limit of elasticity. For metallic and ceramic materials, the elastic region shows a linear relationship between stress and strain, but for polymers the relationship can be nonlinear. The yield strength is dened as the value of the stress when the strain is 0.2% more than the elastic region will allow, i.e., the stress
FIGURE 11-8. The HCP structure of hydroxyapatite.
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FIGURE 11-9. Approximate relation among molecular weight, Tg , Tm , and polymer properties.
level at which 0.2% permanent deformation occurs; this value is also referred to as the 0.2% proof stress. As it is very difcult to determine the onset of permanent or plastic deformation, the yield strength is a more practical property than the limit of elasticity. Plastic deformation (plastic strain) is permanent strain and it occurs beyond the yield strength, as removal of stress leaves the material deformed. The ultimate tensile strength (UTS) is the maximum technical stress (load divided by the original section) the material can sustain in tension. Ductility is the
strain at failure (usually expressed as percent). Fracture toughness is the measure of the energy required to break a material (the area under the stress-strain curve at failure). Fracture toughness varies with the material: it is 0.75 MPam1/2 for silica glass, 4 MPam1/2 for diamond, and up to 100 MPam1/2 for steel. Hardness is another mechanical property. It is the resistance of a material to the penetration of its surface. The fatigue strength is the maximum stress a material can withstand for either an innite or an arbitrary large number of
FIGURE 11-10. Two-dimensional representation of multimolecular polymer structures: Extended chain bers; folded-chain single crystals; glassy polymer amorphous structure; and semicrystalline fringed micelle combination structure. (Reprint with permission from Wunderlich, B. in Crystals of linear macromolecules, ACS Audio Course, American Chemical Society, Washington DC, 1973. Copyright (c) 1973, American Chemical Society.)
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4.2 Fracture Mechanics of Ceramics Biomaterials made of glass or ceramic (e.g., bioactive glass or alumina) fail in a brittle manner. This is a process in which fracture occurs with little or no plastic deformation. Brittle fracture generally occurs by cleavage over particular crystallographic planes (in crystalline structures). Although not applicable here, it is useful to know that at high temperatures, the crystalline component of the ceramic can fail intergranularly. This occurs when grain-boundary shearing takes place and cracks open up between the grains, causing a local stress concentration and ultimate fracture. Fatigue fracture occurs in metals under cyclic stressing by the nucleation and extension of a crack within an extensively deformed area at or near the surface. Such a phenomenon is unlikely in ceramics. However, static fatigue or delayed fracture is common in ceramics. In this case, stress corrosion occurs preferentially at the tip of preexisting defects under the inuence of a static stress. This leads to subcritical crack progression prorated to the time at which the part is stressed. Eventually fracture occurs some time AU: Preceding after the load was rst applied. This kind of frac- sentence OK ture, called fatigue in ceramics, is particularly as edited? sensitive to environmental conditions. The static fatigue is dependent on the total time during which the load is applied, plus the loading rate and the total number of loading cycles. The relationship between the time to failure t and the fracture stress of a material can be described by the equation log t = A/f + B (4)
FIGURE 11-11. Stress deformation curve for a simple tensile test. E, elastic modulus; se , proportionality limit; y.s., 0.02% offset yield stress; U.T.S., ultimate tensile stress; df , total plastic deformation at fracture.
tab.11.3 tab.11.4 tab.11.5
cycles. Usually the number of cycles selected is 10 million. This represents about 10 years of loading a hip prosthesis for a patient with limited activity. As any device is subjected to cyclic loading, designing against fatigue is essential for most orthopaedic implants. Typical mechanical property values of some materials are given in Tables 11-3 and 11-4. Table 11-5 summarizes Youngs modulus for some of the commonly used materials.
TABLE 11-3. TYPICAL VALUES OF TENSILE STRENGTH FOR VARIOUS MATERIALS AT ROOM TEMPERATURE
Material Diamond Kevlar High-strength carbon ber High-tensile steel Superalloy Spider webs (drag line) Ti-6Al-4V CoCr alloy (F75) Aluminum Titanium (Grade 4) 316L SS (F745, annealed) (Cold forged) Bone Nylon Rubber Tensile strength (MPa) 1.05 106 4,000 4,500 2,000 1,300 1,000 860 655 570 550 485 1,351 200 100 100
where A and B are constants. This relationship is not valid at very short times but provides a useful description over a long time period. The fatigue process has been associated with two phenomena: (1) a stress corrosion process, in which a sufciently large stress enhances the rate of corrosion at the crack tip relative to that at the site, leading to a sharpening and deepening of the crack and eventually resulting in failure, and (2) a lowering of the surface energy, , by the adsorption of an active species. This leads to
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TABLE 11-4. FATIGUE PROPERTIES OF IMPLANT METALS

Material Stainless steel ASTM Designation F745 F55, F56, F138, F139 Condition Annealed Annealed 30% cold worked Cold forged As-cast/annealed P/M HIPa Hot forged Annealed 44% cold worked Hot forged Cold worked, aged 30% cold-worked grade Forged annealed Forged, heat treated Fatigue Endurance Limit (At 107 Cycles, R = 1) (MPa) 221280 241276 310448 820 207310 725950 600896 Not available 586 500 689793 (axial tension R = 0.05, 30 Hz) 300 620 620689
Co-Cr alloys
F75 F799 F90 F562
Ti alloys
F67 F136
P/M HIP, Powder metallurgy produced, hot-isostatically pressed.
a decrease in the surface energy contribution to the fracture surface work. However, as the estimated surface energies only represent about 30% of the total fracture surface work, changes in surface energy would not be sufcient to account for the observed long exposure to loads. For this reason, as well as for its generally satisfactory description of many experimental data, the stress corrosion model is preferred. Although static fatigue is closely related to a corrosion process, the dissolution must be of a particular type that leads to slow crack growth, increasing the stress concentration at the crack tip until it grows to a
size that causes fracture. Such phenomena have been reported for alumina and zirconia heads of hip prostheses. Growth of subcritical cracklike defects till they reach a critical size can be prevented by designing for service stresses significantly lower than those for which failure would occur during the life of the device. 4.3 Elastic Properties of Composites It is often useful to stiffen or harden a material, commonly a polymer, by the incorporation of
TABLE 11-5. ELASTIC PROPERTIES OF SOME TYPICAL MATERIALS

Materials Cortical bone Trabecular bone High-density polyethylene PMMA Stainless steel AISI 316L Cobaltchromium alloy Titanium Ti-6A14V Carbon berreinforced graphite bers Alumina Directionality Properties Anisotropic Anisotropic Isotropic Isotropic Isotropic Isotropic Isotropic Isotropic Anisotropic Isotropic Modulus of Elasticity (MPa) Longitudinal axis, 17,000 Longitudinal axis of femur intertrochanteric 316 293 4101,240 3,00010,000 200,000 220,000 107,000 110,000 Parallel to unidirectional 140,000 Single-crystal, 362,700 Polycrystal, 408,900
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particulate inclusions. The shape of the particle is important. In isotropic systems, stiff platelet inclusions are the most effective in creating a stiff composite, followed by ber inclusions. The least effective geometry is a spherical particle. A dilute concentration of spherical particulate inclusions of stiffness Ei and volume fraction Vi , in a matrix, denoted by the subscript m, with a Poissons ratio of 0.5, gives rise to a composite with a stiffness E: E = [5(E i E m )Vi /(3 + 2E i /E m )] + E m (5)
compliant than the matrix, spherical ones reduce the stiffness the least and platelets reduce it the most. In this case platelets resemble cracklike defects, and soft spherical inclusions are used intentionally as crack stoppers to enhance the toughness of polymers, with only a small sacrice in stiffness. 5 WEAR RESISTANCE 5.1 Ultrahigh-molecular-weight Polyethylene Ultrahigh-molecular-weight polyethylene (UHMWPE) (MW above 2 106 g/mol) has long been used for the acetabular cup of total hip prostheses and the tibial plateau and patellar surface of knee prostheses. The success of UHMWPE in these applications is due to its favorable properties, including abrasion resistance, impact strength, low coefcient of friction, chemical inertness, and resistance to stress cracking. Table 11-6 summarizes the mechanical and phy- tab.11.6 sical properties of four different medical grades of UHMWPE: compression molded sheet (1020 CMS); ram extruded bar (1020 REB); partially crystallized 1050 CMS (Poly Hi); and partially crystallized 1050 REB (Poly Hi) (70). In the majority of contemporary total joint replacements, a metallic component articulates against UHMWPE. As a patient may be expected to take an average of 1200 steps per day, the joint replacement is expected to withstand millions of loading cycles during its service lifetime (148). In total hip replacements, where the articulating geometries consist of conforming spherical surfaces, the wear occurs at a microscopic length scale (m or less). Wear resistance has been related to its resistance to
Even if the particles are perfectly rigid compared with the matrix, their stiffening effect at low concentrations is modest. Fibers incorporated in a polymer matrix increase strength and fatigue life, in addition to the stiffness (2). Unidirectional ber composites, when loaded along the bers, can have a strength and stiffness comparable to that of steel, but with much less weight. However, if unidirectional ber composites are loaded transverse to the bers, such a composite will be compliant, with stiffness not much greater than that of the matrix alone. If stiffness and strength is needed in all directions, the bers must be oriented randomly. For such a three-dimensional isotropic composite, E = (E i Vi /6) + E m (6)
Thus, the stiffness is reduced by a factor of about 6 in comparison with an unidirectional composite. However, if the bers are aligned randomly in a plane, the reduction in stiffness is only a factor of 3. Conversely, when inclusions are used to reduce the stiffness and the inclusions are more
TABLE 11-6. MECHANICAL AND PHYSICAL PROPERTIES OF MEDICAL GRADES OF UHMWPE ( STANDARD DEVIATION)
1020 CMS Yield stress (MPa) UTS (MPa) % elongation Impact strength (kJ/m2 ) Density (g/cm3 ) 23.6 0.1 42.1 2.6 396 20 161 1.9 0.9366 0.0001 1020 REB 23.6 0.1 37.2 6.4 376 52 140 1.4 0.9357 0.0001 1050 CMS 22.6 0.1 43.8 3.5 359 20 93.7 3.4 0.9308 0.0003 1050 REB 22.3 0.4 39.9 5.0 354 33 97.9 2.9 0.9332 0.0001
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multidirectional stresses (13,25,62,90,119,120, 137,161165). In total knee replacements, where the articulating surfaces consist of nonconforming cylindrical, toroidal or at surfaces, the wear process includes various surface damage mechanisms ranging from pitting and delamination to burnishing and adhesive wear (5,161, 172,174,175). Focusing on acetabular components and the analysis of retrieved devices, it is evident that there are three different mechanisms of wear. Adhesive wear is a process in which surface asperities of the polymer adhere to the metal surface and subsequently are torn off. As a result either a polymer lm is formed on the metal surface or polymer particles are released and entrapped in the joint. Such particles as well as remaining cement fragments can generate abrasive wear, a second mode of wear. This process can also be generated by asperities on the gliding metal partner. A third mechanism is fatigue wear; as a result of creep or plastic ow, folds or cracks are formed that cause small polymer particles to break off. It is generally accepted that particulate debris generated by mechanical wear (adhesion, abrasion, and fatigue) of prosthetic components stimulates the generation of a pseudosynovial membrane at the interface between implant and bone and the inltration of brocytes and macrophages. In the presence of debris, these cells release various cytokines and mediators (such as IL-1, TNF, collagenase, and prostaglandin E2 ) (69,85,89,155). These cytokines have been shown to be involved in bone resorption by activating osteoclasts (110). A recent study showed a positive correlation between cytokine concentration in the loosening membrane and the degree of underlying osteolysis (153). Many reports have investigated the size of wear debris retrieved from failed total joint arthroplasty (TJA) and demonstrated that phagocytosis and cell mortality increase with particle size and concentration (18). The mechanism that results in this cell death remains unknown, although a potential role for apoptosis in the pathogenesis of wear debris-associated osteolysis has recently been suggested (19). Aseptic loosening, which is the single most common cause for long-term failure of TJA, is associated
with periprosthetic osteolysis with the incidence of up to 25% of implant recipients (59,91,93). The analysis of wear mechanisms in vivo readily points out the importance of the test conditions for the usefulness of wear data collected in vitro. As loading controls the fatigue wear, both the loading cycle and the size and shape of the contact area inuence the wear behavior. Choosing the test solution is no less important, as this also affects the adhesive wear process. It is widely recognized, however, that wear rates produced in hip simulator studies are often lower than those generated in vivo (6,12,22), and this has been explained by a lack of abrasive wear due to roughened heads, third-body particles, and polymer degradation. Although these parameters are clearly inuential in wear debris production, the inuence of alternative gait activities must also be considered. Hip simulator validation studies have correlated the mechanical behavior and surface morphology of polymeric biomaterials with the wear performance (49,50,101). Because of the multidirectional motion prevalent at the articulating surface of total hip prostheses, the mechanical behavior of UHMWPE under multiaxial loading conditions has been shown to provide important insight into the wear resistance (102). Based on equibiaxial tension testing performed on miniature 0.5 mm thick, 6.4 mm diameter disk specimens obtained from the surface of wear-tested cups, work to failure has been significantly correlated with the wear performance in a hip simulator for a wide range of virgin and crosslinked semicrystalline polymers (49,50). Furthermore, the surface morphology of the weartested acetabular components has been related to the mechanical behavior of semicrystalline polymers, in that materials with greater toughness (work to failure) under multiaxial loading conditions were associated with lower surface roughness during hip simulator testing (101). Fig- Fig.11.12 ure 11-12 shows an 8-station hip joint simulator used in some of these studies. Multiple factors can affect polyethylene wear and the production of wear debris in vivo after joint arthroplasty. Such factors include the roughness and material of the femoral head, the method of polyethylene sterilization, and
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FIGURE 11-12. Photographs and schematics showing (A) MTS 8-station hip joint simulator, (B) physiological test setup, (C) fully constraining socket xture, (D) partially constraining socket xture, (E) location of horizontal torque cells, and (F) direction of torque measured.
the mechanical properties of the polyethylene itself (149). The alterations of the mechanical properties of polyethylene associated with gamma irradiation in air and shelf life have been demonstrated in the laboratory (24,26,169). Recent laboratory studies have conrmed that the wear resistance of ultrahigh-molecularweight polyethylene can be signicantly increased when applying additives or high-dose irradiation (21,68,105,121,125,176), with many studies reporting extremely low quantities of wear, typically as low as 2.0 mm3 per million cycles for highly cross-linked polyethylenes. A study undertaken by Laurent et al. (105) reported no measurable wear after 20 million cycles of normal walking and highlights the potential of such materials. Radiographic measurements are also evidencing extremely low in vivo wear rates of cross-linked polyethylene (176), with recent retrieval studies undertaken by Oonishi et al. (130) showing little evidence of in vivo scratching and delamination on sockets irradiated at 100 Mrad. As these materials continue to maintain an acceptable biocompatibility, the overall success of polyethylene hip arthroplasty should greatly increase, thereby offering a highly cost-effective treatment.
5.2 Alumina High-density, high-purity alumina is used in load-bearing hip prostheses because of its outstanding wear resistance and excellent corrosion resistance. It has a high Youngs modulus and a hardness second only to that of diamond. These properties have made the alumina-onalumina couple for femoral heads and acetabular cups a materials combination of considerable importance. Most alumina devices are very ne grained polycrystalline -Al2 O3 produced by pressing and sintering at high temperature (1600 to 1700 C). A very small amount of MgO (less than 0.5%) is used to aid sintering and limit grain growth during sintering. Static and fatigue strength and fracture toughness are a function of grain size and percentage of sintering aid (i.e., purity). Alumina with an average grain size below 4 m and a purity greater than 99.7% exhibits excellent exural and compressive strength. Table 11-7 summarizes these tab.11.7 properties. Studies have reported excellent performance of the alumina on alumina bearing in terms of low annual wear (<5 m) (10,11,124, 128,160,170). The long-term friction of an
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TABLE 11-7. PHYSICAL CHARACTERISTICS OF Al2 O3 BIOCERAMIC

High-alumina Ceramics Alumina content (% by weight) Density (g/cm3 ) Average grain size (m) Surface roughness, Ra (m) Hardness (Vickers hardness number, VHN) Compressive strength (MPa) Bending strength (MPa) Youngs modulus (GPa) Fractures toughness (K1 c) (MPa) >99.8 >3.93 36 0.02 2,300 4,500 550 380 56 56 ISO Standard 6474 99.50 3.90 <7 >2,000 400
Fig.11.13
alumina-alumina joint prosthesis decreases with time and approaches the value of a normal joint. This lead to wear on alumina articulating surfaces being nearly 10 times lower than on polyethylene surfaces gliding against metallic heads (Fig. 11-13). Careful operative technique with correct positioning of the prosthesis is necessary to avoid excessive wear (37,83,113). Impingement between the femoral neck and the rim of the acetabular cup has been associated with massive wear and osteolysis (173) and high wear rates have been associated with stripe and severe wear of Mittelmeier prostheses (127). Nevertheless, given good surgical technique it is possible to achieve very low volumes of wear with ceramicon-ceramic prostheses. Histological studies of the pseudosynovial tissue obtained from around retrieved uncemented ceramicceramic prostheses have identied numerous alumina ceramic particles with a mean size of 5 m (100). In addition, Henssge et al. (79) observed particles up to 5 m in diameter in the periprosthetic tissues from around cemented aluminaalumina prostheses. More recently, very small alumina wear particles in the
size range 5 to 90 nm were revealed by transmission electron microscopy (TEM), whereas SEM (lower resolution) revealed particles in the 0.05 to 3.2 m size range (72). The bimodal size range of alumina ceramic wear debris overlapped with the size ranges commonly observed with metal particles (10 to 30 nm) and particles of ultrahigh-molecular-weight polyethylene (0.1 to 1000 m). It is possible that the two types of ceramic wear debris are generated by two different wear mechanisms in vivo; under normal articulating conditions, relief polishing wear and very small wear debris is produced, while under conditions of microseparation of the head and cup and rim contact, intergranular and intragranular fracture and larger wear particles are generated. The in vivo wear rate of the ceramicceramic joint couple is reported to be up to 200 times less than that of the metalPE joint couple (37). Although ceramics are considered more bioinert than PE ceramic particles generated in vivo, when present in large concentrations, they can initiate an inammatory response in periprosthetic tissue (107,108). Moreover, alumina ceramic particles could induce macrophage
FIGURE 11-13. Time dependence of (solid line) coefcient of friction and (dashed line) index of wear of alumina-alumina versus metal-PE hip joint (in vitro testing). (Reprinted from Hench LL. Bioceramics: from concept to clinic. J Am Ceram Soc 1991;74(7):14871510, by permission of the American Ceramic Society.)
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TNF- release (18,20) and apoptosis (19). Petit et al. (135) compared the macrophage response to identically sized particles of alumina ceramic (Al2 O3 ) and UHMWPE in terms of TNF- release and induction of apoptosis of J774 mouse macrophages. The stimulation of TNF- release was much greater (8 to 10 times higher) with UHMWPE than with Al2 O3 . However, the induction of apoptosis as measured by activation of caspase-3, PARP cleavage, and DNA laddering was different for these two particle compositions, being faster and more important with Al2 O3 than with UHMWPE. One of the highlights of apoptotic cell death, as it applies to periprosthetic osteolysis, is that the whole process terminates in the elimination of dead macrophages without the induction of a significant inammatory reaction (23). Therefore, it could be possible that the ability of Al2 O3 particles to induce macrophage apoptosis may explain the lower TNF- release observed with these particles and explain the differences seen in osteolysis patterns of ceramicceramic versus metalpolyethylene articulations (107). The induction of macrophage apoptosis may therefore be a desirable therapeutic endpoint. 6 METALLIC BIOMATERIALS CORROSION RESISTANCE AND RELATED PROPERTIES Corrosion is the unwanted chemical reaction of a metal with its environment, resulting in its continued degradation to oxides, hydroxides, or other compounds. Biological uids in the human body contains water, salt, dissolved oxygen, bacteria, proteins, and various ions such as chloride and hydroxide. As a result, the human body is a very aggressive environment for metals. Consequently, corrosion resistance of a metallic implant material is an important aspect of its biocompatibility. Metallic biomaterials are normally considered to be highly corrosion resistant because of the presence of an extremely thin passive oxide lm that spontaneously forms on their surfaces. These lms serve as a barrier to corrosion processes in alloy systems that would otherwise experience very
high corrosion rates. That is, in the absence of passive lms, the driving force for corrosion for typical implant alloys [e.g., titanium-based, cobalt chromium (CoCro)-based, and stainlesssteel alloys] is very high, and corrosion rates would also be high. The properties of these passive oxide lms depend to a large extent on their structure and chemistry, which are themselves dependent on the substrates prior thermal, mechanical, and electrochemical history. In this section, the basis for the excellent corrosion resistance of currently used implant metals is explained. There are two CoCr alloys extensively used in implant fabrications such as articial joints, or stems of prostheses for heavily loaded joints such as knees and hips: the castable CoCrMo alloy and the CoNiCrMo alloy, which is usually wrought by (hot) forging. The chromium is a reactive element and is added to produce a stable rmly adherent protective chromium oxide surface layer. Chromium also enhances the solid solution strengthening of the alloy. The molybdenum is added to produce ner grains, which results in higher strengths after casting or forging. As with stainless steel, molybdenum also enhances the corrosion resistance of cobaltchromium alloys (136). The inhomogeneous microstructure of the cast Co-Cr-Mo alloy renders it more susceptible to corrosion than the forged alloy (36), presumably due to the presence of chromium-depleted dendritic regions acting as the more anodic sites in a galvanic reaction. Wrought Co- Cr-Mo has lower carbon content than cast Co-Cr-Mo and, as a result a lower corrosion resistance when tested in physiologic solution (36,82). The metallic products released from the prosthesis because of wear, corrosion, and fretting may impair organs and local tissues, and moreover, some alloys with certain amount of Co can be toxic in the body. Low wear has been recognized as an advantage of metal-onmetal hip articulations because of their hardness and toughness. Both c.p. Ti and Ti-6Al-4V possess excellent corrosion resistance for a full range of titanium oxide states and pH levels. Titanium is a base metal in the context of the electrochemical series; however, it derives its resistance to
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corrosion by the formation of a solid oxide layer to a depth of 10 nm. Under in vivo conditions the oxide, TiO2 is a very stable reaction product. Corrosion currents in normal saline are very low (108 Acm2 ). The low dissolution rate and near chemical inertness of titanium dissolution products allow bone to thrive and therefore osseointegrate with titanium. Titanium implants remain virtually unchanged in appearance; however, even in their passive condition, metals, including titanium, are not inert. It is established beyond doubt, by both in vitro and in vivo experiments (60,73,103, 104,168), that there is a passive dissolution from the metal. Thus, linked to the issue of electrochemical behavior are several questions: (1) What material is released? (2) How much material is released under statistic conditions? (3) How is the release modied by wear conditions? (4) What subsequent reactions do the release products get involved in? (5) What percentage of the release products is excreted and what percentage is retained? (6) Of the percentage that is retained, where does it accumulate? (7) What biological response(s) will result from the retained fraction (14,15,44,48,96,122,166)? Stainless steel contains enough chromium to confer corrosion resistance by passivity. The passive layer (chromium oxide) is not as robust as in the case of titanium or the cobaltchromium alloys. The relatively resistant varieties of stainless steel are the austinitic types 316, 316L, and 317, which contain molybdenum (2.5% to 3.5%). Even these types of stainless steels are vulnerable to pitting and to crevice corrosion around screws, under certain circumstances such as in a highly stressed and oxygen-depleted region (4). The corrosion resistance can be enhanced by increasing the thickness of the protective oxide using concentrated nitric acid (passivation), by boiling in distilled water, or by electrochemical means (anodization) (87). The reduction of carbon to less than 0.03% has virtually eliminated the risk of intercrystalline corrosion, which can occur when there is precipitation of chromium carbide at the grain boundary in stainless steel with a carbon content above this value (133). Unfortunately, lowering the carbon content results in lowering the ultimate tensile strength of stainless steel.
Corrosion of an implant in the clinical setting can result in symptoms such as local pain and swelling in the region of the implant, with no evidence of infection; only cracking or aking of the implant (seen on roentgenograms), and excretion of excess metal ions. At surgery, gray or black discoloration of the surrounding tissues may be seen and akes of metals may be found in the tissue. Corrosion also plays a role in the mechanical failures of orthopaedic implants. Most of these failures are due to fatigue, and the presence of a saline environment certainly exacerbates fatigue. The extent to which corrosion inuences fatigue in the body is not precisely known, although once an initial crack has formed, crack propagation will be faster than in air or vacuum. Other mechanisms of corrosion such as fretting may also be involved at point of contact such as in the countersink of hip nails. Different parts of the body undergo different types and rates of corrosion. Wounds and infections can signicantly change pH. In vivo, the equilibrium state between a metal and its reaction products (oxide, hydroxide, etc.), which causes passivation, may not occur if the reaction products are removed by the tissue uid turnover. The replenishment of ions accumulated at the implanttissue interface may cause adverse increase in the rate of ion release that may cause damage on the cellular level. Focusing on the major alloying elements in cobaltbased materials (Co, Cr, and Ni), Co and Ni ions bind to serum albumin, and Cr6+ binds to red blood cells (14). Chemical analyses of urine from animals subjected to metal salts indicated that most Co and Ni is rapidly excreted, while less than 50% of the Cr is excreted, and this occurs at a slower rate than Co or Ni (15,123). Furthermore, organ levels of Co and Ni are not signicantly elevated, whereas they are for Cr. Serum and urine analyses of patients with total joint replacements have also indicated a dose response relationship (127). Koegel and Black (96), using a cast Co-Cr-Mo microsphere model, found dose related elevations in serum Co and Cr, with peak concentrations achieved 3 days after implantation. Scaling for the implant surface area to animal body weight ratio (300), the Co and Cr elevations were 20 and 12, respectively. In a related study (166), it was determined that the
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form of the released chromium was Cr6+ , a more biologically active form of Cr than Cr3+ . Black et al. (7) found that when a pyrolytic carbon coating was applied to cast Co-Cr-Mo, the carbon-coated implants released more Co and Cr than the uncoated implants. Relative motion between the implant and tissue may have caused the release of additional debris, possibly in the form of metal carbides. Ducheyne and Healy (44) determined that hydroxyapatite coatings reduce the Ti and Al passive dissolution rate from porous coated Ti-6Al-4V. Hydroxyapatite, however, did not produce a change in the release kinetics of Co and Cr from Co-Cr alloys. Other studies on Ti and Ti-6A1-4V have shown that titanium is preferentially accumulated locally, with elevated levels of Ti detected in adjacent soft tissue and bone (48). Healy and Ducheyne (74) further determined that serum proteins increase the release rate kinetics of titanium compared to solutions containing only serum electrolytes. 7 BONE BIOACTIVE CERAMICS 7.1 Calcium Phosphates Structure, Mechanical Properties, and Processing Bioactive materials including calcium phosphate ceramics and bioactive glasses bond to bone and enhance bone tissue formation. The forms of calcium phosphate ceramics most widely used are tricalcium phosphate [Ca3 (PO4 )2 , whitlockite], tetracalcium phosphate (Ca4 P2 O9 ), and hydroxyapatite [Ca10 (PO4 )6 (OH)2 ] (HA). There is a wide variation of mechanical properties of synthetic calcium phosphates as given in Table 11-8. This variation of properties is the result of variation of density and crystalline structure of calcium phosphates, in turn the result of differences in processing methods. Sintering of calcium phosphate ceramics is usually carried out in the range of 1000 to 1500 C. Depending on the nal ring conditions, the calcium phosphate can be hydroxyapatite or -whitlockite. In many instances however, both types of chemistries exist in the same nal product. The phases formed at high temperature depend not only on the sintering temperature but
also on the partial pressure of water in the sintering atmosphere. This is because with water present, HA can be formed and is a stable phase up to 1360 C as shown in the phase equilibrium diagram for CaO and P2 O5 with 500 mm Hg partial pressure of water (Fig. 11-14). The tem- Fig.11.14 perature range of stability of HA increases with the partial pressure of water, as does the rate of phase transition of tricalcium phosphate or tetracalcium phosphate to hydroxyapatite. The ideal Ca/P ratio of hydroxyapatite is 10:6 and the calculated density is 3.219 g/cm3 . Hydroxyapatite has a high elastic modulus (40 to 117 GPa), whereas the elastic modulus of compact bone is 12 to 18 GPa. Poissons ratio for hydroxyapatite is about 0.27, which is close to that of bone (approximately 0.3). At body temperature only two calcium phosphates are stable when in contact with aqueous media such as body uids. At pH less than 4.2, the stable phase is CaHPO4 2H2 O (dicalcium phosphate or brushite), whereas at pH greater than 4.2 the stable phase is HA. 7.2 Calcium Phosphates Biological Behavior Daculsi et al. used transmission electron microscopy to determine the in vivo degradation of biphasic implant materials which were various mixtures of hydroxyapatite and tricalcium phosphate (27). Implants were inserted in surgically created periodontal defects. At 6 months, a direct correlation was established between the rate of dissolution of the material and the quantity of newly formed microcrystals with Ca/P ratios similar to those of bone apatite. The transmission electron microscopical studies carried out by Jarcho et al. (88) and Tracy and Doremus (156), who each used dense, stoichiometric hydroxyapatite, showed direct apposition of bone crystals onto the synthetic apatite lattice. Whereas in these studies solid-solution ion exchange was not addressed, Davies et al. (32) documented in a more recent study a limited in vivo reactivity of this material. A similar result of limited reactivity of dense, stoichiometric hydroxyapatite was also found by Schepers et al. (145), who implanted granules of this material in various bone tissue sites of the
Au: Permission to reproduce?
tab.11.8
LI005-11 Mow and Huskies August 14, 2004
P1: IML/FFX
P2: IML/FFX
QC: IML/FFX
TABLE 11-8. MECHANICAL PROPERTIES AND STRENGTH OF CALCIUM PHOSPHATE CERAMICS

Porosity (%) Density (mg/m3 ) Youngs Modulus (GPa) Microhardness (GPa) Compressive Strength (MPa) Tensile Strength Strength (MPa) Flexural (MPa)
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Hydroxyapalite
18
Tetracalcium phosphate Triacalcium phosphate
Other calcium phosphates
0.13 10 30 40 2.819.4 2.526.5 Dense Dense 36 Dense
3.053.15 2.7 2.553.07 3.1 3.14 2.83.1
713 4488 55110
4.24.5 4.2
350450 120170 60120 310510 800 120200 120 721 70170
3848 5
100120 1535 60115 50115
Au: Pls. check strength repeat on 7th TCH from left
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hydroxyapatite (145). Osteoconduction from the bone defect wall occurred over a limited distance and bone tissue conduction into the center of the defects was not observed. In addition, a chronic, mild multinucleated cell resorption of the material started as early as 3 months after implantation. This limited osteoconductivity is attributed to the high stability of the hydroxyapatite ceramic in tissue uids which results in a considerable induction time for precipitation of a fresh apatite layer from the interfacial tissue uids onto the material surface. Another factor which contributes signicantly to the delay
FIGURE 11-14. Phase equilibrium diagram of calcium phosphates in a water atmosphere. Shaded area is processing range to yield HA-containing implants.
Fig.11.15
beagle mandible. Bone tissue grew from the preexisting bone along the particles that were closest to the defect wall. However, bone tissue did not grow further than about 1 mm into the defect after about 12 weeks. In addition, the presence of multinucleated cells was continuously observed from that time on, and the ceramic surface exhibited a moth-eaten appearance resulting from the local resorption of the material. In the areas where multinucleated cells were present, there was no new bone tissue formation. Osteoconduction and multinucleated cell-mediated resorption frequently had taken place on separate sides of a single particle. These phenomena are shown in Fig. 11-15a and b. This experiment showed beyond doubt that dense, stoichiometric hydroxyapatite is osteoconductive in vivo. However, it also revealed that this material displays only a limited bone bioactivity. If a key element for bone bioactive behavior is the development of a carbonated apatite surface, one might expect an excellent response by using a carbonated apatite as implant material. However, implantation data do not unequivocally support this hypothesis. The tissue response to a porous carbonated apatite material implanted in beagle mandibular bone was very similar to that with dense, stoichiometric
B
FIGURE 11-15. Histological section of dense, stoichiometric hydroxyapatite. (A) After 3 months, bone tissue has grown along the particle surface, but only over a distance of about 1 mm. (B) From 6 months on, the particle surfaces have a moth-eaten appearance caused by multinucleated cell resorption. The resorption is not paralleled by a bone formation process (Reprint from Schepers E, Declercq M, Ducheyne P, Kempeneers R. Bioactive glass particulate material as a ller for bone lesions. J Oral Rehab 1991;18:439 452, with permission.)
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in the formation of the bioactive apatite surface layer is protein adsorption. 7.3 Calcium Phosphates Coatings Coating metallic prostheses with a calcium phosphate layer provides direct implantbone bonding and better xation and longevity. When a porous stainless-steel ber network was coated with a slip-cast HA lining, a marked increase in bone ingrowth was observed in comparison to the ingrowth in the same porous metal without HA lining. This effect was pronounced at 2 and 4 weeks, but it disappeared at 12 weeks (45). This phenomenon provided the distinct therapeutic benet of faster rehabilitation for patients with HA-coated devices. However, structural and compositional changes of the Ca-P ceramic occur as a result of processing of the coatings. These variations of the material characteristics affect the rate of enhancement of the bioactive ceramic coating. Using an experimental protocol that extensively controlled factors such as animal model, pore size, pore morphology, and properties of the metallic substrate, it was found that there were statistically signicant variations in bonding strength in the rst few weeks after implantation arising from differences in ceramic characteristics (40). Figure 11-16 shows that calcium-phosphate coatings signicantly enhanced bone tissue growth xation, but that the effect differed among coatings. In addition, these data show that the intensity of the effect was consistent among the three early time points studied. The clinical experience with HA coatings has been excellent. Most trials have focused on the performance of the femoral component. There has been variability in the implant design studied, the method and characteristics of the applied coatings, and the extent of the coating on the surface of femoral stems (64). There have been numerous cohort studies but few randomized clinical trials (29,30,65,66,143). Larger uncontrolled series have reported valuable results (17,29,65). DAntonio et al. reported a multicenter study of 316 hips (280 patients) with a proximally hydroxyapatite-coated titanium alloy
FIGURE 11-16. Shear strength as a function of implantation time for controls (porous-surfaced titanium) and porous specimens with various calcium phosphate coatings. Note that the greatest effect on bone tissue ingrowth xation is associated with coating CAP3, which is the coating with the highest in vitro dissolution rate (Reprint from Ducheyne P, Beight J, Cuckler J, Evans B, Radin S. Effect of calcium-phosphate coating characteristics on early post-operative bone tissue ingrowth. Biomaterials 1990;11:531540, with permission.)
Fig.11.16
stems that were implanted in a young and active patient population from 1987 through 1990 (31). Clinically, these patients had early pain relief and rapid restoration of function. The results show excellent lasting xation of this tapered titanium alloy stem coated proximally with a thin, dense layer of hydroxyapatite. Another report by Hernandez et al. described the 11-year follow-up results of 52 unilateral primary hip arthroplasties performed with hydroxyapatitecoated stems (80). The femoral prosthesis used was a collarless titanium alloy implant, with proximal circumferential hydroxyapatite coating and increased distal thickness to t the proximal diaphyseal region of the femur. At the end of the follow-up period, excellent clinical results were recorded in 40 arthroplasties (77%). The 11-year survival rate was 92.3%. Geesink and Hoefnagels (66) reported their 6-year results of 118 primary total hip arthroplasties using a metaphysis lling Ti stem that had a 50-mthick air plasma sprayed coating of hydroxyapatite on the proximal third of its surface. The studys reported survival rate of the prosthesis at 6 years was 100% for the 118 hydroxyapatite coated stems and 99% for the hydroxyapatitecoated cups. Vidalain reported a 0.97 survival rate of the Corail femoral stem at 10 years of
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implantation (158). This survival rate is considered to be even higher than that of many series of Charnley prostheses, which remain the absolute standard in this respect. During that period (10 years), more than 6,700 implantations have been performed and analyzed by the surgeons of the ARTRO Group, with a consistent annual rate of about 700 replacements. Functional results have been rated as excellent using the Postel Merle dAubign or Harris hip scores. According e to the PMA hip scale, the preoperative score was 11.29; it was 17.01 at 1 year, 17.21 at 5 years, and 17.20 at 10 years. Actually, scores are very similar to those achieved with the best cemented prostheses, particularly for pain, with the absence of signicant thigh pain, which is typical of the CORAIL hip prosthesis. Altogether, 63% of patients are totally pain free and have recovered normal motion and function. Based on these clinical results it is concluded that osteoconductive coatings have established an excellent performance record in primary and revision hip arthroplasty. In view of all the advantages of hydroxyapatite coating, are there drawbacks or at least concerns or questions? It is now well established that hydroxyapatite is not toxic, does not produce inammatory or allergic reactions, and is not carcinogenic. Still, four problems can be discussed: HA resorption and long-term stability, osteolysis that is occasionally observed, polyethylene wear and potential risk of granuloma, and the difculty of extracting an HA-coated stem, particularly when it is perfectly ingrown. Resorption of hydroxyapatite is more or less inescapable, due to both chemical dissolution and cell-mediated degradation. However, the kinetics of this degradation process is inuenced by a number of factors which are still not clearly understood, and consequently, are not all well known. Aebli et al. carried out a histological study of a proximally hydroxyapatite (HA)coated femoral component, retrieved after 9.5 years of good function (1). The HA coating had completely degraded. Bone was in direct contact with the titanium surface in all the areas which had been coated, with no interposing brous tissue. There were no signs of particles, third-body wear, adverse tissue reactions, or osteolysis. Bone
remodeling was evident by the presence of resorption lacunae; tetracycline labeling showed bone laid down 6 years after implantation. The loss of the HA coating had no negative effect on the osseointegration of the stem. It was concluded that the HA coating contributes to the xation of the implant and that its degradation does not adversely affect the long-term xation. HA, when rst used as a hip stem coating more than 10 years ago, was considered sufciently insoluble at neutral pH not to be degraded after implantation. However, it then became apparent that the HA was decomposed during plasma spraying. Several phases (- or -TCP, CaO, TTCP, oxyapatite, and amorphous calcium phosphate) can be evidenced in the HA coating after spraying. These different phases occur in various amounts and at preferential locations in the coating depending on plasma-spray parameters and powder characteristics. CaO, for example, is found at the interface with the metal, whereas the contaminating calcium phosphate phases occur around the crystalline phase of the coating grains. Most of the contaminating phases are more soluble than HA at neutral pH and their presence in the HA coating increases its degradability. The coating environment is also determinant in coating degradation. The dielectric constant and pH of the extracellular uids are key factors and can be modied by cell activity. The pH can, for example, be modied by osteoclast activity, the pH in the resorption chamber of osteoclasts being as low as 4.5 to 5. Similar low-pH compartments are found in cytoplasmic compartments such as lysosomes. These different factors explain the degradation of calcium phosphate coatings evidenced in contact with or in the close vicinity of osteoclasts, macrophage, or giant cells. Degradation of the calcium phosphate coatings constituted by the stacking of calcium phosphate grains occurs preferentially at the interface between the grains, where the most soluble phases facilitating the release of calcium phosphate particles are located. Particle release by a material implanted in bone is a cause of concern due to the osteolytic reactions that have been evidenced in the vicinity of metal or polymeric particles debris. Furthermore, Bloebaum et al. (8)
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suggested that the calcium particles emitted by acetabular coatings could migrate to the surface of polyethylene cups, thereby triggering thirdbody wear responsible for osteolysis and aseptic loosening. When HA-coated metallic implants have been retrieved from humans and animals, evidence has been found of loose HA particles and osteolysis (3,9,28,42,63). Bloebaum et al. reported that histologic evaluation of 14 retrieved implants revealed HA particles, evidence of inammatory reactions and osteolysis (9). Furthermore, resorption of HA can create a void between the metal implant and the surrounding bone matrix (151), which may lead to mechanical instability and eventual failure. Reikeras et al. reported the outcome of 191 acetabular gritblasted titanium cups with a hemispherical design for press-t insertion and coated with hydroxyapatite (139). The prosthesis was made of gritblasted titanium entirely coated with hydroxyapatite. The 155 patients, aged 15 to 78 years, were operated on during the years 1991 to 1993 and followed for 7 to 10 years. During this period, 39 cups were revised because of mechanical loosening, a further nine had radiolucent lines, and two had focal osteolysis. None of these 11 patients had clinical symptoms. Failure was associated with age, wear, and radiolucency/osteolysis. At revision, it was found that the soft tissues were discolored, and that most of the coating had disappeared. It has been concluded that this design of hydroxyapatite-coated cups has a high rate of debonding and failure. Regardless of these reports, the overall clinical benet of calcium phosphate coatings has been decidedly positive. Basic science studies proved that next-generation biomimetic hydroxyapatite coatings will expand the application range of os-
teoconductive coatings to three-dimensional ingrowth structures and combinations with antibiotics, growth factors, or other achievements of modern biotechnology. 7.4 Bioactive Glasses Bioactive glasses are silica-based glasses in which silica (SiO2 ) is the network former and alkali metals, e.g., Na and K, or alkaline earth metals, e.g., Ca and Mg, are the network modier. The ratio of network former to network modier in the composition of bioactive glass determines its solubility in physiological solutions and hence its bioactivity and resorbability. Table 11-9 summarizes the chemical composition tab.11.09 of selected bioactive glasses and glass ceramics with different degrees of bioactivity. The amorphous structure of bioactive glass impairs its mechanical strength and lowers its fracture toughness. Tensile strength of most of the bioactive glass compositions in Table 11-9 is in the range 40 to 60 MPa, which makes them unsuitable for load-bearing applications. For some applications low strength is offset by the glasses low modulus of elasticity of 30 to 35 Gpa, which is close to that of cortical bone (7 to 25 GPa). A unique characteristic of bioactive glass is its ability to form a strong interfacial bond with adjacent tissues in the host, and it has been used successfully as a bone-substitute material in orthopedic and dental surgery (131,147, 150,152,171). To understand the basic mechanisms of the formation of the bonebiomaterials bond, two main approaches were considered. One focused on studying the bone biomaterials interface that developed in vivo. The examination of bonding zone revealed the
TABLE 11-9. COMPOSITION OF BIOACTIVE GLASSES AND GLASS CERAMICS (IN WEIGHT PERCENT)
Type Bioactive glass Code 45S5 45S5F 55S4.3 Ceravital A-W GC SiO2 45 45 55 4050 34.2 CaO 24.5 12.5 19.5 3035 44.9 Na2 O 24.5 24.5 19.5 510 P 2 O5 6 6 6 1015 16.3 MgO 2.55 4.6 K2 O 0.53 CaF2 12.5 0.5
Bioactive glass ceramic
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into apatite on surface [either hydroxycarbonate apatite (HCA) or uorapatiteCO3 2 or F from solution]. These reactions, however, does not occur as such in vivo or in vitro in the presence of proteins, the HA layer does not form on the glass surface. Only when osteoblasts are present on the bioactive glass surface does the HA surface form again, evidently as a result of cellular activity Leaching of Na+ (or K+ ) into solution (i.e., (5357). exchange with H+ or H3 O+ from solution) and There is a good correlation between the abilformation of SiOH (silanol): ity of a biomaterial to develop a hydroxyapatite surface layer in acellular SBF and its ability to SiONa + H+ + OH SiOH bond to bone. Therefore, the degree of bioac+ Na+ (solution) + OH tivity of biomaterials is evaluated based on their Loss of soluble silica (SiO2 ) and formation of ability to develop a hydroxyapatite surface layer SiOH: in vitro. As already stated, this does not necessarily imply that the above dissolutionprecipiSiOSi + H2 O SiOHHO + Si tation reactions take place at the materialtissue uid interface in vivo. In addition to the major Polycondensation of silanols to form hy- difference in composition between tissue uid drated silica gel: and SBF as shown in Table 11-10, there is a tab.11.10 considerable difference in the parametric condiOSiOH + HOSiO OSiO tions under which the above reactions take place SiO + H2 O in vivo and in vitro. It is obvious from Table 11-10 that one canFormation of amorphous calcium phosnot expect that the material behavior in vitro is phate layer: Ca2+ and PO4 3 migrate to the similar to that in vivo, especially in the rst few surface through the SiO2 -rich layer, forming a days after implantation where the wound healing CaOP2 O5 -rich layer on top of the SiO2 gel layer mechanism is in effect. Figure 11-17 schemati- g.11.17 (the CaOP2 O5 layer proceeds to grow by incally shows a variety of events that were reported corporation of soluble Ca2+ and PO4 3 from to occur at the bioactive ceramictissue interface solution). (41). The list does not imply a ranking in terms In the absence of proteins and bone cells the of time sequence or importance: (1) dissolution amorphous calcium phosphate layer crystallizes from the ceramic (35,47,78,94,106,126,134);
TABLE 11-10. DIFFERENCES IN MEDIUM COMPOSITION AND PARAMETRIC CONDITIONS UNDER WHICH THE BIOACTIVITY REACTIONS AT THE BIOMATERIAL SURFACE TAKE PLACE IN VIVO AND IN VITRO
Parameter Cellularity Protein content Replenishment Variation in solution composition during contact pH Temperature SBF (Simulated Body Fluid) Acellular No protein Non Limited to dissolutionprecipitation 7.4 37 C Tissue Fluid Highly cellular Protein-rich Fluid turnover (blood circulation) Unlimited, due to chemotaxis and macrophage activity Could reach 9 due to wound healing mechanism Could reach 40 C due to wound healing processes
consistent presence of an interfacial hydroxyapatite layer (78,126). The other approach used in vitro immersions in simulated physiological uids or cell-containing media (99,77,53). Upon immersion of bioactive glass in acellular, simulated body uids (with ionic concentration and pH similar to the interstitial uid) the following reactions take place (77):
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FIGURE 11-17. Schematic diagram representing the events which take place at the interface between bioactive ceramics and the surrounding biological environment (Reprint from Ducheyne P, Bianco P, Radin S, Schepers E, Bioactive materials: mechanisms and bioengineering considerations. In: Ducheyne P, Kokubo T, van Blitterswijk CA, eds. Bone-bioactive biomaterials. Leiderdorp, The Netherlands: Reed Healthcare Communications, 1993:112, with permission.)
(2) precipitation from solution onto the ceramic (27,34,106,126,134); (3) ion exchange and structural rearrangement at the ceramic-tissue interface (3,27,34,78,126,145); (4) interdiffusion from the surface boundary layer into the ceramic (46); (5) solution-mediated effects on cellular activity (71,86,129,145,159); (6) deposition of either the mineral phase (a), or the organic phase (b), without integration into the ceramic surface (27,33,34,55,106); (7) deposition with integration into the ceramic (27, 106,145); (8) chemotaxis to the ceramic surface (145); (9) cell attachment and proliferation (33,71,86,118); (10) cell differentiation (145); and (11) extracellular matrix formation (33,55,118). The observation of what transpires at the interface, however, does not represent a mechanistic explanation for the effect which bioceramics have on bone tissue formation. We can focus on mechanisms by relying on an increasing body of evidence which suggests that bone bonding and bone tissue ingrowth enhancement are the result of multiple, parallel, and sequential reactions at the materialtissue interface. These interactions either are related
to physicochemical phenomena that occur in the presence or absence of cells, or are related to reactions affected by cellular activity. An important aspect of the overall reaction sequence between these materials and tissues is that, in the absence of a biologically equivalent, calciumdecient, carbonate-containing hydroxyapatite (HCA) surface upon implantation, dissolution, precipitation, and ion-exchange reactions lead to a biologically equivalent apatitic surface on the implanted material. This reaction does not proceed by itself, but is accompanied by parallel reactions, such as adsorption and incorporation of biological molecules and attachment of surrounding cells. Furthermore, cells that have adhered to the ever-reacting material surface interact with the material and produce some of the surface changes. In the inverse direction, i.e., from material to environment, there is both a solution-mediated and a surface-controlled effect on cellular activity, organic matrix deposition, and mineralization. The gradual change of the ceramic surface to become a biologically equivalent HA with small crystal dimensions is a rate-determining step in the cascade of events underlying bioactive behavior. All phenomena,
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collectively, lead to the gradual incorporation of the bioactive implant into developing bone tissue. 7.5 Bioactive Glass Ceramics Approaches to achieving enhanced mechanical and biochemical properties included transformation of bioactive glass into glass-ceramic, and using bioactive glass as a coating on a substrate or as a second phase in a composite combining the characteristics of both into a new material (77). In these techniques, bioactive glass is subjected to thermal treatments which alter the materials microstructure and limit its biological activity. Thermal treatment of bioactive glass (45S5) in the temperature range 550 to 680 C resulted in the formation of Na2 Ca2 Si3 O9 crystals (61). Raising the treatment temperature to 800 C led to the development of calcium phosphate crystals similar to the structure of hydroxyapatite (78). Other investigators showed that when bioactive glass in the system MgO-CaO-SiO2 -P2 O5 was thermally treated, the glass transformed into apatite/wollastonite (A-W) glass ceramic (97). According to powder X-ray diffraction, the crystallized glass consisted of 38% apatite, 34% wollastonite, and 28 wt% residual glassy phase (97). The resulting bioactive A-W glass ceramic is characterized by a high mechanical strength (Table 11-11) and has been used successfully for load-bearing prostheses (75, 98,177). However, in vivo studies showed that the improved mechanical strength of bioactive glass ceramic is at the expense of the rate of bone bonding to the material (98,109). An important change in the glass microstructure, which usually precedes crystallization, is the
TABLE 11-11. PHYSICAL PROPERTIES OF A-W BIOACTIVE GLASS CERAMIC
Density (g/cm3 ) Bending strength (MPa) Compressive strength (MPa) Youngs modulus (GPa) Vickers hardness (HV) Fracture toughness (MPa 1/2) 3.07 215 1,080 118 680 2.0
glass-in-glass phase separation (112). After separation, the glass no longer has a homogeneous composition, but rather, consists of two or more immiscible glassy phases of different chemical constituents. Unlike crystallization, phase separation in glass might not be visible by optical microscopy and in most cases can be detected only by electron microscopy. Previous work revealed that thermal treatment of bioactive glass at 550 C resulted in glass-in-glass phase separation and minor crystallization (58). These changes in bioactive glass microstructure altered the corrosion behavior and led to a signicant increase in the negative ZP of the material. In conjunction with the increase in negative ZP there was a signicant decrease in the amount of serum protein adsorption onto the material surface. The inhibition of protein adsorption could be responsible for the slow rate of bone bonding to bioactive glass ceramic. It is also possible that conformation changes inhibited the activity of the protein adsorbed onto thermally treated bioactive glass. Moreover, alteration of corrosion behavior after bioactive glass crystallization delayed the formation of the hydroxyapatite surface layer necessary for bone bonding. 8 TISSUE ENGINEERING AND RECENT DEVELOPMENTS 8.1 Bone Tissue Engineering The eld of tissue engineering has recently emerged as a result of growing understanding of the mechanism of action of biomaterials in vitro and in vivo combined with latest advances in cell isolation, culture procedures, molecular biology, and biochemistry techniques. Tissue engineering offers a promising new approach to repair fractures that do not heal, major bone loss, and fractures associated with bone tumors. In this approach, a porous scaffold that seeds the cells can serve as a vehicle to deliver cells necessary for tissue regeneration. With this approach, it is possible to use the patients own cells so that immunosuppression is not needed. The design of a scaffolding material can significantly affect the cell seeding and growth both
tab.11.11
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in vitro and in vivo (111). Scaffolding materials should be biocompatible and biodegradable. The degradation products should be nontoxic and easily excreted by metabolic pathways. The scaffold material should be mechanically strong to maintain structural integrity during culture. The ideal scaffolding materials also should be easy to fabricate into a desired shape and have a controlled porous architecture to allow for cell growth, tissue regeneration, and vascularization. The scaffolding materials should be osteoconductive so that osteoblasts and osteoprogenitor cells can adhere, migrate on the scaffolds, differentiate, and synthesize new bone matrix. The new tissue should also have the potential to grow and remodel, which is especially important for pediatric patients. Use of degradable scaffolds to support cell proliferation and extracellular matrix synthesis implies a transient microenvironment that may inuence cell behavior. Poly(-hydroxyl acids), such as poly(L-lactic acid) (PLLA), poly(glycolic acid) (PGA), and poly(D,L-lactic acid-co-glycolic acid) (PLGA), satisfy many of these material requirements and already have been fabricated into scaffolds for cell transplantation and tissue engineering (81,84,178,179). One of the disadvantages of these materials is that the degradation products reduce the local pH value, which, in turn, may accelerate the polyesters degradation rates (157) and induce an inammatory reaction. Another disadvantage is that the mechanical properties of the highly porous scaffolds made from poly(-hydroxyl acids) are relatively weak, which limits their use for bone-tissue regeneration, especially in the in vivo implant site. Incorporation of HA with PLLA resulted in a compact composite with little porosity and improved mechanical strength. By monitoring for 24 weeks the pH value variations during their incubation in phosphate-buffered saline (PBS), it has been found that the pH value of PLLA/HA composite is more stable than that of pure PLLA and pure HA (142,167). Hydroxyapatite ceramic and its composites are composed of the same ions as bone and are considered to be suitable candidate materials for the synthesis of bone tissue engineering scaffold. However, hydroxyapatite ceramic,
which is stoichiometric hydroxyapatite, resorbs very slowly or remains unchanged in bone sites (95,114,115). Bioactive glass (45S5) is an attractive scaffold material because it stimulates osteoprogenitor cell function and possesses controlled resorbability (39,43,52,55,76,146). The goal is to use the in vitro synthesized bone as a graft material to treat major bone loss in orthopedic or maxillofacial surgery. Modication of the bioactive glass surface before cell seeding serves two goals: (1) to minimize the adverse effect on medium pH due to the accumulation of the bioactive glass degradation products and (2) to create the bioactive hydroxyapatite surface layer, which otherwise will not form in the presence of serum. It was discovered that the calcium phosphate layer that forms on the surface of bioactive glass is highly selective toward adsorption of serum bronectin, an attachment protein known to enhance osteoblast adhesion and activity (53,54). Other bioactive materials such as hydroxyapatite ceramic or unmodied bioactive glasses do not have any selectivity toward bronectin. Thus, when bone cells were cultured on bioactive glass pretreated to be covered with a dual layer of calcium phosphate and serum protein, abundant and expeditious bone tissue was formed on and within the porous template. Figure 11-18 is a scanning electron micrograph Fig.11.18 of the cross section of porous BG showing the formation of extracellular matrix and bonelike tissue after 7 days in culture. The cells also exhibited a high alkaline phosphatase activity and synthesized collagen type I and osteocalcin (57). 8.2 Engineering Surfaces with Peptides Adherence of osteoblasts to a biomaterial surface is dependent on topography, chemistry, and surface energy. Cell attachment activity is also related to a tripeptide sequence, arginine-glycineaspartic acid (RGD), located in the cell-binding domain of many adhesion molecules (144). Following attachment, there is reorganization of cytoskeletal proteins, resulting in the attening and spreading of the cell and formation of focal contacts, replete with clustered integrins. This form of cytoskeletal organization participates in cell
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FIGURE 11-18. SEM micrograph of the fractured surface of the porous modied bioactive glass template seeded with neonatal rat calvaria osteoblasts for 7 days. Note the uniform formation of extracellular matrix and bonelike tissue throughout the porous disk. (With permission from El-Ghannom A, Ducheyne P, Shapiro IM. Bioactive material template for in vitro systhesis of bone. J Biomed Mater Res 1995;29:359370.)
signaling events and serves to regulate cell behavior (67). However, the adsorption of attachment proteins may not be successful in promoting long-term cell attachment to biomaterials in vivo because of several limitations. These include protein desorption and/or exchange and denaturation, the removal of the oligopeptide sequences due to proteolysis, difculties in controlling the sequence presentation (i.e., C- or N-terminus binding), and specically arranging a sequence or a series of sequences on the surface (117,138). In order to derivatize in a stable manner the surfaces with RGD-sequence peptides, covalent immobilization of the active peptide is necessary. The use of covalently coupled small peptide mimics allows control over the density and orientation of ligand attachment. Many investigators have bound RGD peptides to polymeric surfaces and evaluated cell activity (116,132). These studies have shown that the chemistry of the surface layer can modify the conformation of the peptide and thereby change its interaction with cells. For example, Drumheller and Hubbell showed that complete cell spreading on poly(ethylene glycol) networks required a peptide density three orders of magnitude greater than that required for silanated glass (38). A 15-mer peptide containing the RGD
motif grafted onto a quartz surface enhanced the strength of bone cell attachment and promoted spreading and focal contact formation (141). In a parallel investigation, the surface of quartz was engineered to contain different ratios of cell binding (RGD) and heparin binding (FHRRIKA-) domains (140). It was found that heterogeneous peptides containing RGD and -FHRRIKA in the ratio 75:25 or 50:50 enhanced cell spreading and mineralization compared to homogenous surfaces containing either RGD or FHRRIKA. Results of the studies discussed above provide evidence that the immobilized peptides containing the RGD sequence serve to enhance cell attachment to polymeric and ceramic surfaces. In most cases, the biomaterial exhibits a new topography, surface chemistry, and functionality depending on the modication strategy. Even the method chosen to activate the surface (e.g., wet versus dry chemistry) can alter the biomaterial surface properties. Cell behavior on surfaces grafted with the minimal tripeptide RGD devoid of any anking groups or spacers was investigated. Using an atomically smooth silicon substrate covered with a reproducible oxide layer, the oxide surface was activated using 3-aminopropyl triethoxysilane (APTS) (51). This layer exhibited nanoscale roughness and presented amine
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functional groups for grafting the RGD tripeptide. The attachment of RGD to the APTS surface was conrmed by time-of-ight secondary ion mass spectrometry analyses. Contact angle measurements indicated that the hydrophobicity of the APTS surface was signicantly lower than that of the surface with grafted RGD (RGD-APTS). Atomic force microscopy roughness measurement values showed that surfaces covered with RGD-APTS were smoother (Ra = 0.71 nm) than those covered with APTS alone (Ra = 1.59 nm). MC3T3-E1 bone cells were seeded on these various substrates and incubated in a serum-free medium for different periods of time. Whereas attachment was similar on both APTS and RGD-APTS surfaces, cell spreading and cytoskeletal organization were clearly favored on the relatively smooth grafted peptide surface. Thus, neither surface roughness nor the amine group alone of the APTS layer account for improved cellbiomaterial interaction. These data suggest that the combination of surface roughness and RGD modication provides the most favorable surface for cell spreading and cytoskeletal organization. These events signicantly enhanced downstream maturationrelated activities such as those linked to cytodifferentiation and mineralization of the extracellular matrix. REFERENCES
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A. El-Ghannam, P. Ducheyne Biomaterials In: Basic Orthopaedic Biomechanics and Mechanobiology Eds., Van C.

Mow and Rik Huiskes, Lippincott-Williams and Wilkens, 2005

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THE MATERIALS SCIENCE TRIAD 00 CLASSES OF MATERIALS 00

2.1 2.2 2.3 2.3

Metals 00 Ceramics 00 Polymers 00 Composites 00

Metals and Ceramics 00 Polymers 00

4.1 4.2 4.3

Mechanical Properties 00 Fracture Mechanics of Ceramics 00 Elastic Properties of Composites 00

Bone Tissue Engineering 00 Engineering Surfaces with Peptides 00

5.1 Ultrahigh-molecular-weight Polyethylene 00 5.2 Alumina 00

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permission from publishers to use all reproduced gures?

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Polymer bers Metal wire

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FIGURE 11-6. Geometric representation of the seven atomic lattices.

FIGURE 11-7. FCC and HCP crystal lattices.

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FIGURE 11-8. The HCP structure of hydroxyapatite.

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tab.11.3 tab.11.4 tab.11.5

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TABLE 11-4. FATIGUE PROPERTIES OF IMPLANT METALS

F75 F799 F90 F562

P/M HIP, Powder metallurgy produced, hot-isostatically pressed.

TABLE 11-5. ELASTIC PROPERTIES OF SOME TYPICAL MATERIALS

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