Bioceramics: From Concept to Clinic Larry L. Hench* Department of Materials Science and Engineering, University of Florida, Gainesville, Florida 3261 1 Ceramics used for the repair and re- mechanical reliability under load is construction of diseased or damaged still needed. [Key words: bioceramics, parts of the musculo-skeletal sys- structure, dental ceramics, interfaces, tem, termed bioceramics, may be bio- mechanics.] inert (alumina, zirconia), resorbable (tricalcium phosphate), bioactive (hy- droxyapatite, bioactive glasses, and glass-ceramics), or porous for tissue 1. Introduction ingrowth (hydroxyapatite-coated met- MANYmillennia ago, the discovery of als, alumina). Applications include re- human kind that fire would irreversibly placements for hips, knees, teeth, transform clay into ceramic pottery led tendons, and ligaments and repair for eventually to an agrarian society and periodontal disease, maxillofacial re- an enormous improvement in the qual- construction, augmentation and stabi- ity and length of life. Within the last lization of the jaw bone, spinal fusion, four decades another revolution has and bone fillers after tumor surgery. occurred in the use of ceramics to im- Carbon coatings are thromboresistant prove the quality of life. This revolution and are used for prosthetic heart is the innovative use of specially de- valves. The mechanisms of tissue signed ceramics for the repair and re- bonding to bioactive ceramics are be- construction of diseased or damaged ginning to be understood, which can parts of the body. Ceramics used for result in the molecular design of bio- this purpose are termed bioceramics. ceramics for interfacial bonding with Bioceramics can be single crystals hard and soft tissues. Composites are (sapphire), polycrystalline (alumina or being developed with high toughness hydroxyapatite (HA)), glass (Bio- and elastic modulus match with bone. glass@*),glass-ceramics (Ceravital@+ Therapeutic treatment of cancer has or A/W glass-ceramic), or composites been achieved by localized delivery of (stainless-steel-fiber-reinforced Bio- radioactive isotopes via glass beads. glass@ or polyethylene-hydroxyapatite Development of standard test methods (PE-HA)). for prediction of long-term (20-year) Ceramics and glasses have been used for a long time in the health-care R E Newnham-contributing editor industry for eye glasses, diagnostic in- struments, chemical ware, thermome- Manuscript No. 196865 Received March 3, 1991; ters, tissue culture flasks, and fiber approved April 23, 1991. optics for endoscopy. Insoluble porous Supported by U.S. Air Force Office of Scientific Research under Contract No F496290-88-C-0073. glasses have been used as carriers for The conducted research was reviewed and ap enzymes, antibodies. and antigens proved by the University of Florida Institutional since they have several advantages, Animal Care and Use Committee to ensure that notably resistance to microbial attack, the research procedures adhered to the standards set forth in the Guide for the Care and Use of pH changes, solvent conditions, tem- Laboratory Animals (NIH Publication 85-23) as perature, and packing under the high promulgated by the Committee on Care and Use pressure which is required for rapid of Laboratory Animals of the Institute of Labora- tory Animal Resources. Commission on Life Sci- ences, National Research Council. *University of Florida, Gainesville, FL %rnber, American Ceramic Society. 'Leitz Gmbh, Wetrlar. FRG 1487 1488 Journal of the American Ceramic Society - Hench Vol. 74, No. 7 flow.' Ceramics are also widely used in formation of an interfacial bond of im- dentistry as restorative materials, gold plants with bone (Fig. l(b)).4Figure l(b) porcelain crowns, glass-filled ionomer will be discussed in more detail in Sec- cements, dentures, etc. In these appli- tion VIII. cations they are called dental ceram- The relative level of reactivity of an ics as discussed by Preston.' implant influences the thickness of the This review is devoted to the use of interfacial zone or layer between the bioceramics as implants to repair material and tissue. Analysis of failure parts of the body, usually the hard tis- of implant materials during the last sues of the musculo-skeletal system, 20 years generally shows failure origi- such as bones or teeth, although a nating from the biomaterial-tissue in- brief review of the use of carbon coat- terfa~e.~,~When a biomaterial is nearly ings for replacement of heart valves is inert (type 1 in Table I1 and Fig. 1) and Table I. Types of Implant-Tissue also included. Dozens of ceramic com- the interface is not chemically or bio- logically bonded, there is relative Response positions have been tested;',3 however, few have achieved human clinical ap- movement and progressive develop- If the material is toxic, the surrounding plication. It is now known that clinical ment of a nonadherent fibrous capsule tissue dies. success requires the simultaneous in both soft and hard tissues. Move- If the material is nontoxic and bio- achievement of a stable interface with ment at the biomaterial-tissue inter- logically inactive (nearly inert), a connective tissue and a match of the face eventually leads to deterioration in fibrous tissue of variable thickness mechanical behavior of the implant with function of the implant or the tissue at forms. the tissue to be replaced. the interface or both. The thickness of If the material is nontoxic and bio- the nonadherent capsule varies greatly II. Twes-. of Bioceramics-Tissue depending upon both material (Fig. 2) logically active (bioactive), an inter- Attachment facial bond forms. and extent of relative motion. The mechanism of tissue attachment The fibrous tissue at the interface with dense, medical-grade alumina im- the surrounding tissue replaces it. response at the implant interface.' No plants can be very Consequently, material implanted in living tissues is as discussed later, if alumina implants inert; all materials elicit a response are implanted with a very tight me- from living tissues. The four types of re- chanical fit and are loaded primarily in sponse (Table I) allow different means compression, they are successful clini- of achieving attachment of prostheses cally. In contrast, if a type 1, nearly to the musculo-skeletal system. Table II inert, implant is loaded such that inter- summarizes the attachment mecha- facial movement can occur, the fibrous nisms, with examples. capsule can become several hundred A comparison of the relative chemi- micrometers thick and the implant cal activity of these different types of loosens quickly. Loosening invariably bioceramics is given in Fig. 1. The leads to clinical failure, for a variety of relative reactivity shown in Fig. I(a) reasons, including fracture of the im- correlates very closely with the rate of plant or the bone adjacent to the implant. Bone at an interface with Table II. Types of Bioceramics a type 1, nearly inert, implant is very -Tissue Attachment and Bioceramic Classification often structurally weak because of Type of disease, localized death of bone (es- bioceramic Type of attachment Example pecially if so-called bone cement, 1 Dense, nonporous, nearly inert Al2O3 (single crystal and poly(methy1 methacrylate (PMMA) is ceramics attach by bone polycrystalline) used), or stress shielding when the growth into surface higher elastic modulus of the implant irregularities by cementing prevents the bone from being loaded the device into the tissues, properly. or by press fitting into a The concept behind nearly inert, defect (termed morphologi- microporous bioceramics (type 2 in cal fixation). Table II and Fig. 1) is the ingrowth of 2 For porous inert implants A1203 (porous polycrystalline) tissue into pores on the surface or bone ingrowth occurs, Hydroxyapatite-coated porous throughout the implant, as originated by which mechanically metals Hulbert et aL3 many years ago. The in- attaches the bone to the creased interfacial area between the material (termed biological implant and the tissues results in an fixation). increased inertial resistance to move- 3 Dense, nonporous, surface- Bioactive glasses ment of the device in the tissue. The reactive ceramics, glasses, Bioactive glass-ceramics interface is established by the living and glass-ceramics attach Hydroxyapatite tissue in the pores. Figure 3 shows liv- directly by chemical ing bone grown into the pores of an bonding with the bone alumina bioceramic. This method of (termed bioactive fixation). attachment is often termed biological 4 Dense, nonporous (or porous), Calcium sulfate (plaster of Paris) fixation. It is capable of withstanding resorbable ceramics are Tricalcium phosphate more complex stress states than type 1 designed to be slowly Calcium phosphate salts implants, which achieve only morpho- replaced by bone. logical fixation." The limitation associ- ated with type 2 porous implants, however, is that, for the tissue to remain July 1991 Bioceramics: From Concept to Clinic 1489 viable and healthy, it is necessary for which have evolved over millions of the pores to be greater than 100 to years. Complications in the develop- 150 pm in diameter (Fig. 2). The large ment of resorbable bioceramics are interfacial area required for the porosity (1) maintenance of strength and the is due to the need to provide a blood stability of the interface during the supply to the ingrown connective tissue. degradation period and replace- Vascular tissue does not appear in ment by the natural host tissue and pores which measure less than 100 pm. (2) matching resorption rates to the If micromovement occurs at the inter- repair rates of body tissues (Fig. I(a))> face of a porous implant, tissue is which themselves vary enor mousl y. damaged, the blood supply may be cut Some dissolve too rapidly and some off, tissues die, inflammation ensues, too slowly. Because large quantities of and the interfacial stability can be de- material may be replaced, it is also es- stroyed. When the material is a metal, sential that a resorbable biomaterial the large increase in surface area can consists only of metabolically accept- provide a focus for corrosion of the im- able substances.