Bone vol, 19, No. I, Supplement uly1996:121s-128s CERAMICS: PAST, PRESENT, AND FUTURE lack e. Lemons Ph. D. The University of Alabama at Birmingham Birmingham, AL 35294-000 ABSTRACT The selection and application of synthetic materials for surgical implants has been directly dependent on the biocompatibility profiles of specific prosthetic devices. The early rationale for ceramic biomaterials was based upon the chemical and biochemical inertness (minimal bioreactivity) of elemental compounds constituted into structural forms(materials). Subsequently, mildly reactive (bioactive), and partially and fully degradable ceramics were identified for clinical uses Structural forms have included bulk solids or particulates with and without porosities for tissue ingrowth, and more recently, coatings onto other types of biomaterial substrates. The physical shapes selected were application dependent with advantages and disadvantages determined by the basic material and design properties of the device construct; and (2) the patient-based functional considerations. Most of the ceramics(bioceramics)selected in the 1960s and 1970s have continued over the long-term, and the science and technology for thick and thin coatings have evolved significantly over the past decade. Applications of ceramic biomaterials range from bulk(100%)ceramic structures as joint and bone lacements to fully or partially biodegradable substrates for the controlled delivery of pharmaceutical drugs, growth factors, and morphogenetically inductive substances. Because of the relatively unique properties of bioceramics, expanded uses as structural composites with other biomaterials and macromolecular biologically-derived substances are anticipated in the future KEY WORDS: Biomaterials, Biocompatibility, Bioceramics, Composites, Surgical Implants, INTRODUCTION Definitions One definition of biocompatibility(as related to biomaterials) which has been generally accepted was pro Williams(46) as an outcome of a consensus conference. Biocompatibility application. Another int y of a material to perform with an appropriate response in a specific was defined as interpretation of the word biocompatibility"has been based upon the interaction(s) between the synthetic substances and the local and systemic tissues. In this respect interactions have been correlated with conditions of minimal harm, or change, cither to the host or to he device construct. This exposition is based, in part, upon conditions of relative inertness(minimal Address for corresponde nd reprints: J. E. Lemons, Ph. D, The University of Alabama at Birmingham, 509 Medical Education Build ing, 1813 Sixth Avenue South, Birmingham, AL 35294-0007 o 1996 by Elsevier Science Inc. PIS87563282
ELSEVIER Bone Vol. 19, No. 1, Supplement July 1996:1219-1288 CERAMICS: PAST, PRESENT, AND FUTURE Jack E. Lemons, Ph. D. The University of Alabama at Birmingham Birmingham, AL 352944007 ABSTRACT The selection and application of synthetic materials for surgical implants has been directly dependent upon the biocompatibility profiles of specific prosthetic devices. The early rationale for ceramic biomaterials Iwas based upon the chemical and biochemical inertness (minimal bioreactivity) of elemental cornpounds constituted into structural forms (materials). Subsequently, mildly reactive (bioactive), and partially and fully degradable ceramics were identified for clinical uses. Structural forms have included bulk solids or particulates with and without porosities for tissue ingrowth, and more recently, coatings onto other types of biomaterial substrates. The physical shapes selected were application dependent, with advantages and disadvantages determined by: (1) the basic material and design properties of the device construct; and (2) the patient-based functional considerations. Most of the ceramics (bioceramics) selected in the 1960s and 1970s have continued over the long-term, and the science and technology for thick and thin coatings have evolved significantly over the past decade. Applications of ceramic biomaterials range from bulk (100%) ceramic structures as joint and bone replacements to fully or partially biodegradable substrates for the controlled delivery of pharmaceutical drugs, growth factors, and morphogeneticahy inductive substances. Because of the relatively unique properties of bioceramics, expanded uses as structural composites with other biomaterials and macromolecular biologically-derived substances are anticipated in the future. KEY WORDS: Biomaterials, Biocompatibility, Bioceramics, Composites, Surgical Implants, Synthetics INTRODUCTION Definitions One definition of the word biocompatibility (as related to biomaterials) which has been generally accepted was provided by Williams(46) as an outcome of a consensus conference. Biocompatibility was defined as “the ability of a material to perform with an appropriate response in a specific application.” Another interpretation of the word “biocompatibility” has been based upon the interaction(s) between the synthetic substances and the local and systemic tissues. In this respect, interactions have been correlated with conditions of minimal harm, or change, either to the host or to the device construct. This exposition is based, in part, upon conditions of relative inertness (minimal Address for corresponhnce and reprints: J. E. Lemons, Ph.D., The University of Alabama ;at Birmingham, 509 Medical Education Building, 1813 Sixth Avenue South, Birmingham, AL 35294-0007. 0 1996 by Elsevier Science Inc. All rights reserved. 121s 8756-3282/96/$15.00 PII S8756-3282(96)00128-7
122S J E Lemons Bone vol. 19. No. 1 Ceramics: Past, present, and future chemical interaction). This condition was one of the criteria used for the initial selection of dense, high-technology ceramic materials The idea that chemical and biochemical inertness could be directly correlated with biocompatibility was emphasized during the late 1960s and early 1970s. 43)This situation changed by the 1980s to an emphasis on controlled interactions(biointegration) between the synthetic biomaterials and the directly ssociated tissues. during the 1990s, the emphasis on which conditions might provide more optimal biocompatibility profiles evolved further, to include chemical and mechanical anisotropy of the synthetic biomaterials (38)This has resulted in more selections of structural combinations(modular) or composite(chemically bonded) biomaterials. Ceramic, metallic, and polymeric biomaterials are often utilized together to provide improved combinations of construct characteristics. The general chronologically-based opinions about changes over the past three decades are summarized in Table 1 TABLE 1. Chronological Interpretations of Biocompatibility Profiles for Synthetic Biomaterials 19 60s 1970s 1980s 19903 Concerns about Emphasis on chemical Controlled interactions Combination and biodegradation and biochemical and integration composite biomaterial products from metals, inertness(bioinert) between biomaterials combinations that alloys, and polymers and tissues(bioactivity provide chemically and or biointegration anisotropic substrates that are more similar to the tissues replaced From a theoretical viewpoint, ceramic biomaterials offer several advantages for musculoskeletal implants and direct interactions with bone. For example, the high purity bioceramics can: (1)be constituted from elements that are normal to human biological environments; (2) provide controlled ()provide controlled electrical and thermal conductivities; ( 4)be utilized as an inert interface or as a arrier(coating) between foreign materials and tissues; (5) provide densities and colors that are similar to bone and teeth; and( 6) provide elastic moduli that are similar to bone. 5,28.47) The overall interpretation of biocompatibility characteristics from a bioengineering(biomaterial and biomechanical) viewpoint includes considerations of element and force transfers between the prosthesis and the tissues (29)This concept is shown schematically in Figure 1. The multiple idea(s) intended to be conceptualized in this figure are to emphasize characteristics that should be considered hen evaluating biomaterial and tissue biocompatibility profiles. Most importantly, the tissue responses to elements(surface area)and force(directions)are directly interrelated and the interfacial interactions listed in Figure 1 cannot be simply isolated from one another However, the relative mportance sof the various factors can be evaluated and understood through controlled laboratory loboratory animal, and human investigations of surgical implant biomaterials and devices. In such experiments, the role(s)of device design and function versus the materials of construction must be controlled independently to minimize confounding variables. This has been done for many ations of bioceramics, however, the overall literature is complicated by minimal levels of pre nd post-implantation biomaterial characterizations. This is especially truc for the active and biodegradable biomaterials, in part because active bioceramics are susceptible to different sterilization (steam autoclave)and surgical placement (handling) conditions. In this experimental conditions(methods and procedures) should be reviewed carefully as prior experiences are critically evaluated Another aspect of biocompatibility evaluations, taken from histological analyses of bioceramic-to-bone nterfaces, is that optical microscopic histological information alone does not normally provide enough information to isolate the specific influences of element- or force-dependent interactions. Additional
122s J. E. Lemons Bone Vol. 19, No. 1, Supplement Ceramics: Past, present, and future July 1996:1218-1283 chemical interaction). This condition was one of the criteria used for the initial selection of dense, high-technology ceramic materials. The idea that chemical and biochemical inertness could be directly correlated with biocompatibility was emphasized during the late 1960s and early 197Os.(43) This situation changed by the 1980s to an emphasis on controlled interactions (biointegration) between the synthetic biomaterials and the directly associated tissues. During the 199Os, the emphasis on which conditions might provide more optimal biocompatibility profiles evolved further, to include chemical and mechanical anisotropy of the synthetic biomaterials(38) This has resulted in more selections of structural combinations (modular) or composite (chemically bonded) biomaterials. Ceramic, metallic, and polymeric biomaterials are often utilized together to provide improved combinations of construct characteristics. The general, chronologically-based opinions about changes over the past three decades are summarized in Table 1. TABLE 1. Chronological Interpretations of Biocompatibility Profiles for Synthetic Biomaterials 1960s I 1970s Concerns about Emphasis on chemical biodegradation and biochemical products from metals, inertness (bioinert) alloys, and polymers 1960s Controlled interactions and integration between biomaterials and tissues (bioactivity or biointegration) 1990s Combination and composite biomaterial combinations that provide chemically and mechanically anisotropic substrates that are more similar to the tissues replaced From a theoretical viewpoint, ceramic biomaterials offer several advantages for musculoskeletal implants and direct interactions with bone. For example, the high purity bioceramics can: (1) be constituted from elements that are normal to human biological environments; (2) provide controlled structures to influence local interactions, including attachment (biointegration) along device interfaces; (3) provide controlled electrical and thermal conductivities; (4) be utilized as an inert interface or as a barrier (coating) between foreign materials and tissues; (5) provide densities and colors that are similar to bone and teeth; and (6) provide elastic moduli that are similar to bone.(5*28,47) The overall interpretation of biocompatibility characteristics from a bioengineering (biomaterial and biomechanical) viewpoint includes considerations of element and force transfers between the prosthesis and the tissues.(2g) This concept is shown schematically in Figure 1. The multiple idea(s) intended to be conceptualized in this figure are to emphasize characteristics that should be considered when evaluating biomaterial and tissue biocompatibility profiles. Most importantly, the tissue responses to elements (surface area) and force (directions) are directly interrelated and the interfacial interactions listed in Figure 1 cannot be simply isolated from one another. However, the relative importance(s) of the various factors can be evaluated and understood through controlled laboratory, laboratory animal, and human investigations of surgical implant biomaterials and devices. In such experiments, the role(s) of device design and function versus the materials of construction must be controlled independently to minimize confounding variables. This has been done for many investigations of bioceramics, however, the overall literature is complicated by minimal levels of preand post-implantation biomaterial characterizations. This is especially true for the active and biodegradable biomaterials, in part because active bioceramics am susceptible to different sterilization (steam autoclave) and surgical placement (handling) conditions. In this regard, the details of experimental conditions (methods and procedures) should be reviewed carefully as prior experiences are critically evaluated. Another aspect of biocompatibility evaluations, taken from histological analyses of bioceramic-to-bone interfaces, is that optical microscopic histological information alone does not normally provide enough information to isolate the specific influences of element- or force-dependent interactions. Additional
J, E. Lemons 23S July1996:21S-128s Ceramics: Past, present, and future Biomaterial-to-Tissue Interface Type, structural form, on, Compression and oxidation and Strains reaction ind Dynamics, Strain Amount, Rate of transfer Time, Rate, Elastic and Times and Dynamics of Viscoelastic Dynamics, Tissue Attachment Functional demands IG. I. Schematic representation of element and force transfers along tissue interfaces and the relative mportance of biomaterial and tissue properties analytical techniques are required to interpret the separate (or combined) roles of the element or force fers along the interfa This paper will provide a chronological review of ceramic biomaterials utilized for load bearing orthopacdic and dental implant devices. The theoretical concepts provided in the introduction will be utilized to present opinions about past experience(s) associated with about interfaces between bioceramics and bone CHRONOLOGICAL REVIEW AND ANALYSIS OF CERAMICS FOR SURGICAL IMPLANTS (1960 THROUGH 1995) 19608 Historical records from implantations of natural minerals (gemstones), ivory, inert metals, and bone products(31. 45) provided a strong and relatively positive background for the consideration of high purity ceramics. Smith and coworkers(39)made a critical step in the early 1960s when they propose to use an aluminum oxide(al2O3) ceramic and epoxy composite where surface porosity was intended to provide tissue ingrowth and a dynamic biological attachment to bone. This material was called Cerosium@a and was patented for orthopaedic and dental surgical applications. In the late 1960's Klawitter, Hulbert, and coworkers(21,25)demonstrated that the surface porosity dimensions of Cerosium@(approximately 25 um maximum cross-section) were inadequate to provide stable vascularized attachments to bone. Klawitter, (2D) working with highly porous (50 volume percent) calcium aluminate ceramics containing various porosity dimensions, demonstrated that minimum cross-section porosity dimensions needed to be 75-100 um or greater to support vascularization and bone ingrowth stability. These data were subsequently confirmed and extended for aluminum oxides by Lyng and coworkers(32)and for porous metallic systems by Hirschorn(I7), Wheeler(44),Rostoker etal., aIn) and Bobyn and coworkers. (2) Hulbert and coworkers(25)provided an insightful summary and supported the importance of relative nertness for ceramics with regard to long-term biodegradation, while simultaneously proposing that ceramics implanted into bone were chemotactic to cells, thus leading to osteointegration. This concept of combining inert ceramics, porosity, and stable bone ingrowth for attachment of the prosthetic device surface is shown diagramatically in Figure 2. The overall rationale for selection of the inert bioceramic was based on more optimal in vivo chemicalbiochemical stabilities which would not 3M Corporation, Minneapolis, MN
Bone Vol. 19, No. 1, Supplement J. E. Lemons July 1996:1219-1283 Ceramics: Past, present, and future 1235 Biomaterial-to-Tissue Interface Type, structural form, oxidation (valence), / reaction products, secondary interactions Elements (Synthetic Biomaterials) \ Amount, Rate of Transfer, Times and Dynamics of Exchange Tension, Compression and Shear Stresses and Strains, Tissue Aging and Dynamics, Strain Energy Density \ Force (Biomechanics) Time, Rate, Elastic and Visioelastic Dynamics, / Tissue Attachment, Functional Demands “~foD,m‘ FIG. 1. Schematic representation of element and force transfers along tissue interfaces and the relative importance of biomaterial and tissue properties. analytical techniques are required to interpret the separate (or combined) roles of the element or force transfers along the interface. This paper will provide a chronological review of ceramic biomaterials utilized for load bearing orthopaedic and dental implant devices. The theoretical concepts provided in the introduction will be utilized to present opinions about past experience(s) associated with about interfaces between bioceramics and bone. CHRONOLOGICAL REVIEW AND ANALYSIS OF CERAMICS FOR SURGICAL IMPLANTS (1960 THROUGH 1995) 1960s Historical records from implantations of natural minerals (gemstones), ivory, inert metals, and bone products(31~4~~) provided a strong and relatively positive background for the consideration of high purity ceramics. Smith and coworkers@) made a critical step in the early 1960s when they proposed to use an ahuninum oxide (A1203) ceramic and epoxy composite where surface porosity was intended to provide tissue ingrowth and a dynamic biological attachment to bone. This material was called Cerosium@a. and was patented for orthopaedic and dental surgical applications. In the late 1960’s, Klawitter, Hulbert, and coworkers( 21y25) demonstrated that the surface porosity dimensions of Cerosium@ (approximate 1 y 25 pm maximum cross-section) were inadequate to provide stable vascular&d alttachments to bone. Klawitter,c21) working with highly porous (~50 volume percent) calcium aluminate ceramics containing various porosity dimensions, demonstrated that minimum cross-section porosity dimensions needed to be 75-100 pm or greater to support vascularization and bone ingrowth stability. These data were subsequently confirmed and extended for aluminum oxides by Lyng and coworkers@) and for porous metallic systems by Hirschorn(l7), Wheeler(44), Rostoker et, aI., and Bobyn and coworkers.(2) Hulbert and coworkers(25) provided an insightful summary and supported the importance of relative inertness for ceramics with regard to long-term biodegradation, while simultaneously proposing that ceramics implanted into bone were chemotactic to cells, thus leading to osteointegration. This concept of combining inert ceramics, porosity, and stable bone ingrowth for attachment of the prosthetic device surface is shown diagramatically in Figure 2. The overall rationale for selection of the inert bioceramic was based on more optimal in vivo chemical/biochemical stabilities which would not a. 3M Corporation, Minneapolis, MN
4s. E Lemons Bone vol. 19. No. 1, S Ceramics: Past, present, and future July 1996: 12Is adversely influence the regional tissues due to biodegradation products. Biomechanically, the porosity and ingrowth region were intended to increase interface arca and redistribute functional forces to thereby provide a stable dynamic attachment for mechanical longevity → Force Bone Porous biomaterial ( Prosthetic Device) FIG. 2. Schematic representation of a cross-section through a porous inert bioceramic utilized for bone ingrowth and attachment of a prosthetic device. The idea of altered force transfer conditions is one intent of this schematic Questions about porosity topologies(connectives), porous surface coatings versus fully port components,and the optimal biomaterials for selected designs and applications were addressed in several investigations (9, 15,30, 37) Relative interconnectivity of porosities to support vascularization ind bone ingrowth were shown to be critical for long-term tissue interface maintenance. Some of the studies on limited connectiveness( dead-end holes)demonstrated that when bone partially filled the depths, the bone ingrowth would remodel to surface zones. The concept of surface irregularities such as grooves, undercuts, porous surface coatings, threads, plateaus, etc. was thereby strongly supported for some implant applications. This was especially valid where implant bulk strength was critical factor. For example, featured surfaces on polycrystalline alumina and single crystalline sapphire were extensively investigated for dental and orthopaedic implant applications. (7, 8, 14, 42) These higher modulus inert bioceramics demonstrated biocompatibility characteristics, although the inherent brittleness of these bioceramics was recognized as a significant limitation with respect to load bearing device designs Another aspect of ceramic, glass, or glass-ceramic systems was the idea of introducing altered chemistries along surfaces, so that bone interactions would result in a bonded zone and chemical biochemical attachment (7)Hench and coworkers(15)investigated a sodium-silicon-lithium glass that was altered with calcium and phosphorous additions. This biomaterial was named BioGlass b.and investigations demonstrated attachments between bone and simulated prostheses(16)These interactions(attachments) were mediated through a silica-based gel and exchanges between the BioGlass@ and bone components. In theory, if the interfacial bonding could be achieved under b. ABC Biomaterials. Florida
124s J. E. Lemons Bone Vol. 19, No. 1, Supplement Ceramics: Past, present, and future July 1996:121S-128s adversely influence the regional tissues due to biodegradation products. Biomechanically, the porosity and ingrowth region were intended to increase interface area and redistribute functional forces to thereby provide a stable dynamic attachment for mechanical longevity. FIG. 2. Schematic representation of a cross-section through a porous inert bioceramic utilized for bone ingrowth and attachment of a prosthetic device. The idea of altered force transfer conditions is one intent of this schematic. Questions about porosity topologies (connectives), porous surface coatings versus fully porous device components, and the optimal biomaterials for selected designs and applications were addressed in several investigations.( ~~1~~30~37) Relative interconnectivity of porosities to support vascularization and bone ingrowth were shown to be critical for long-term tissue interface maintenance. Some of the studies on limited connectiveness (dead-end holes) demonstrated that when bone partially filled the depths, the bone ingrowth would remodel to surface zones. The concept of surface irregularities such as grooves, undercuts, porous surface coatings, threads, plateaus, etc. was thereby strongly supported for some implant applications. This was especially valid where implant bulk strength was a critical factor. For example, featured surfaces on polycrystalline alumina and single crystalline sapphire were extensively investigated for dental and orthopaedic implant applications.(7,8J4342) These higher modulus inert bioceramics demonstrated biocompatibility characteristics, although the inherent brittleness of these bioceramics was recognized as a significant limitation with respect to load bearing device designs. Another aspect of ceramic, glass, or glass-ceramic systems was the idea of introducing altered chemistries along surfaces, so that bone interactions would result in a bonded zone and chemicalbiochemical attachment.t7) Hench and coworkers(15) investigated a sodium-silicon-lithium glass that was alteted with calcium and phosphorous additions. This biomaterial was named BioGlass@b and investigations demonstrated attachments between bone and simulated prostheses.(I@ These interactions (attachments) were mediated through a silica-based gel and exchanges between the BioGlass@ and bone components. In theory, if the interfacial bonding could be achieved under b. ABC Biomaterials, Florida
Bone Vol. 19, No. 1, Supplement J E Lemons 125S Juy1996:12lS128 Ceramics: Past, present, and future normal implant applications and the attachments were stable under normal functional loading conditions, the need for porosity and tissue ingrowth for attachment would be minimized 1970-1980 The earlier studies of Klawitter and Hulbert on porous calcium aluminates(21, 25)demonstrated an interactive non-mineralized surface zone between the ingrown bone and ceramics. This region wa explained by an abnormal pH(alkaline) region immediately adjacent to these particular ceramic surfaces. Graves, Bajpai, and coworkers(, 13, 16)supported the concept of partially ceramic substrates based on various calcium aluminates. These were evaluated primarily as porous materials for bone grafting plus as a surface coating on prosthetic devices. A investigators(18, 19, 26,27,33, 35 )proposed highly porous tricalcium phosphate(TCP)ceramics for the same type applications. The porous TCP ceramic particulates, from Driskell and coworkers(27),for bone graft applications, included a larger dimension porosity region for bone ingrowth plus a smaller dimension microporosity within the primary structural regions of the ceramic. The microporosity was biodegradation of the TCP ceramic. Another aspect of the TCP-type bioceramics was the idea that the bioceramic biodegradation products would favorably influence the interfacial tissue responses. This idea was similar to the concepts of Hench and coworkers except that the BioGlass@ reaction products implant. This same general idea, of limited interactions over time(bioactivity), was also proposed by Doremus, Jarcho and coworkers(4, 22, 23)for a calcium phosphate ceramic that was eventually marketed as Durapatite @e, one form of calcium hydroxyapatite(CHAP). These investigators developed dense (nonporous) crystalline, small grain size, irregularly-shaped particulates of CHAP ceramics Laboratory animal experiments subsequently showed relatively stable particulates of durapatite in dog bones for follow-up times extending to eight years. Related studies also demonstrated regions of epitaxially-oriented bone and CHAP crystals located adjacently along implant interfaces. Multiple theories supported attachment(bonding ) to bone under functional implant conditions The overall idea of combining bioactive ceramics and macroporosity for tissue ingrowth was introduced and investigated for particulates as a component of bone grafting procedures.(3, 24, 34 36) One group synthesized polyphase(biphasic) mixtures of CHAP and TCP into single bioceramic particulate forms, based on the concept that partial biodegradation of the tCP phase would enhance short-and long-term implant applications for bone augmentation and replacement. a number of other ceramics were introduced and evaluated during this period ( 24)This extended to oxide ceramics of aluminum(alumina), zirconium(zirconia), and titanium(titania); complex polyphase spinels and related ceramics; polycrystalline carbon, carbon-silicon, graphites and diamond; metallic carbides and nitrides; and a number of glass-ceramic biomaterials( Ceravital@d., aw-ceramic @ e etc. ) An overall summary of the bioceramics investigated during this period have been provided in several references. (9, 15,21, 36, 38, 42, 47) In general, these early studies provided the basis for the introduction of a wide range of ccramic-based biomaterials for surgical implant applications. 1980 The overall concept for more optimal biocompatibility profiles moved during the 1980s from an emphasis on inert substrates to limited bioactivity and biointegration between the bioceramic surfac and the bone. Biointegration with bone was also proposed for titanium oxide surfaces on unalloyed (3) studies demonstrated that oxide surfaces of several types could achieve stable interfaces with bone for load bearing dental implant devices (6.20) op, NY d. E Leitz and Co., Germany Electric Glass Co. Ja
Bone Vol. 19, No. 1, Supplement J. E. Lemons July 1996:121S-1283 Ceramics: Past, present, and future 125s normal implant applications and the attachments were stable under normal functional loading conditions, the need for porosity and tissue ingrowth for attachment would be minimized. 1970-1980 The earlier studies of Klawitter and Hulbert on porous calcium aluminates(2f~25) demonstrated an interactive non-mineralized surface zone between the ingrown bone and ceramics. This region was explained by an abnormal pH (alkaline) region immediately adjacent to these particular ceramic surfaces. Graves, Bajpai, and coworkers(l*13*16) supported the concept of partially biodegradable ceramic subslrates based on various calcium aluminates. These were evaluated primarily as porous materials for bone grafting plus as a surface coating on prosthetic devices. A number of investigators’:18,19,26,27,33,35) proposed highly porous tricalcium phosphate (TCP) ceramics for the same type applications. The porous TCP ceramic particulates, from Driskell and coworkers(27), for bone graft applications, included a larger dimension porosity region for bone ingrowth plus a smaller dimension r&croporosity within the primary structural regions of the ceramic. The microporosity was deliberately included to enhance fluid penetration through the structure and subsequent time dependent biodegradation of the TCP ceramic. Another aspect of the TCP-type bioceramics was the idea that the bioceramic bjodegradation products would favorably influence the inter-facial tissue responses. This idea was simiJa.r to the concepts of Hench and coworkers except that the BioGlass@ reaction products and tissue responses were intended to be self-limiting with the bulk BioGlass@ retained as a stable implant. This same general idea, of limited interactions over time (bioactivity), was also proposed by Doremus, Jarcho and coworkers(4$22v23) for a calcium phosphate ceramic that was eventually marketed as Durapatite@ c , one form of calcium hydroxyapatite (CHAP). These investigators developed dense (nonporous) crystalline, small grain size, irregularly-shaped particulates of CHAP ceramics. Laboratory animal experiments subsequently showed relatively stable particulates of Durapatite@ in dog bones for follow-up times extending to eight years. Related studies also demonstrated regions of epitaxially-oriented bone and CHAP crystals located adjacently along implant interfaces. Multiple theories supported attachment (bonding) to bone under functional implant conditions. The overall idea of combining bioactive ceramics and macroporosity for tissue ingrowth was introduced and investigated for particulates as a component of bone grafting procedures.(3~24~34,36) One group synthesized polyphase (biphasic) mixtures of CHAP and TCP into single biocenunic particulate forms, based on the concept that partial biodegradation of the TCP phase would enhance short- and long-term implant applications for bone augmentation and replacement. A number of other ceramics were introduced and evaluated during this period.(24) This extended to: oxide ceramics of aluminum (alumina), zirconium (zirconia), and titanium (mania); complex polyphase spinells and related ceramics; polycrystalline carbon, carbon-silicon, graphites and diamond; metallic carbides and nitrides; and a number of glass-ceramic biomaterials (Ceravitalm. , AW-ceramic&. , etc.). An overall summary of the bioceramics investigated during this period have been provided in several references.(9,15,21,36,38.42,47) in general, these early studies provided the basis for the introduction of a wide range of ceramic-based biomaterials for surgical implant applications. 1980s The overall concept for more optimal biocompatibility profiles moved during the 1980s from an emphasis on inert substrates to limited bioactivity and biointegration between the bioceramic surface and the bone.. Biointegration with bone was also proposed for titanium oxide surfaces on unalloyed titanium (Ti) implants by Branemark and coworkers.@) Laboratory, laboratory animal, and clinical studies demonstrated that oxide surfaces of several types could achieve stable interfaces with bone for load bearing dental implant devices.@JO) C. Sterling W:inthrop, NY d. E. J_eitz and Co., Gerrnany e. Nippon Electric Glass Co., Japan