John P. LeGeros

Biphasic calcium phosphate bioceramics: preparation, properties and applications

Biphasic calcium phosphate (BCP) bioceramics belong to a group of bone substitute biomaterials that consist of an intimate mixture of hydroxyapatite (HA), Ca10(PO4)6(OH)2, and beta-tricalcium phosphate (β-TCP), Ca3(PO4)2, of varying HA/β-TCP ratios. BCP is obtained when a synthetic or biologic calcium-deficient apatite is sintered at temperatures at and above 700 °C. Calcium deficiency depends on the method of preparation (precipitation, hydrolysis or mechanical mixture) including reaction pH and temperature. The HA/β-TCP ratio is determined by the calcium deficiency of the unsintered apatite (the higher the deficiency, the lower the ratio) and the sintering temperature. Properties of BCP bioceramics relating to their medical applications include: macroporosity, microporosity, compressive strength, bioreactivity (associated with formation of carbonate hydroxyapatite on ceramic surfaces in vitro and in vivo), dissolution, and osteoconductivity. Due to the preferential dissolution of the β-TCP component, the bioreactivity is inversely proportional to the HA/β-TCP ratio. Hence, the bioreactivity of BCP bioceramics can be controled by manipulating the composition (HA/β-TCP ratio) and/or the crystallinity of the BCP. Currently, BCP bioceramics is recommended for use as an alternative or additive to autogeneous bone for orthopedic and dental applications. It is available in the form of particulates, blocks, customized designs for specific applications and as an injectible biomaterial in a polymer carrier. BCP ceramic can be used also as grit-blasting abrasive for grit-blasting to modify implant substrate surfaces. Exploratory studies demonstrate the potential uses of BCP ceramic as scaffold for tissue engineering, drug delivery system and carrier of growth factors.

Apatite crystallites: effects of carbonate on morphology.

Carbonate is a substituent in the apatite structure; when present, it limits the size of the growing apatite crystals and so influences their shape that they grow more equiaxed than needle-like. The tendency for carbonate apatites to be equiaxed is related to the nature of the chemical bonds formed in the crystal. The interference of carbonate with the good crystallization of apatite, and its weakening effect on the bonds in the structure, increase the dissolution rate and the solubility, thereby presumably contributing to the susceptibility to caries of dental apatites containing carbonate.

Two types of carbonate substitution in the apatite structure.

Um die Art des Karbonateinbaues in die Apatitstruktur zu klären, wurden zwei Typen von synthetischen Karbonatapatiten untersucht: solche, die sich in wässrigen Medien bildeten, und andere, die bei hohen Temperaturen und unter Ausschluss von Wasser entstanden.

Phosphate Minerals in Human Tissues

The mineralized or calcified tissues in biological systems are composed of two phases: organic and inorganic or mineral phases. In the invertebrates (e.g., echinoderms, mollusks, arthropods, etc.), the inorganic phase is usually calcium carbonate, CaCO3, predominantly in the form of either calcite or aragonite or both. In the invertebrates, the inorganic phase consists of one or more types of phosphate minerals (predominantly calcium phosphates) depending on the nature of calcification, i.e., normal (e.g., bones and teeth) or abnormal or pathological (e.g., dental calculi, salivary and urinary stones, soft tissue calcifications, etc.). In several pathologically calcified tissues, the mineral is non-phosphatic, such as calcium oxalates (whewellite and weddellite), sodium urates, uric acid, cysteine.

Simultaneous incorporation of carbonate and fluoride in synthetic apatites: Effect on crystallographic and physico-chemical properties.

The mineral in bone is an impure hydroxyapatite, with carbonate as the chief minor substituent. Fluoride has been shown to stimulate osteoblastic activity and inhibit osteoclastic resorption in vitro. CO(3)- and F-substituted apatite (CFA) has been considered as potential bone graft material for orthopedic and dental applications. The objective of this study was to determine the effects of simultaneously incorporated CO(3) and F on the crystallographic physico-chemical properties of apatite. The results showed that increasing CO(3) and Na content in apatites with relatively constant F concentration caused a decrease in crystallite size and an increase in the extent of calcium release; increasing F content in apatites with relatively constant CO(3) concentration caused an increase in crystallite size and a decrease in the extent of Ca release. These findings suggest that CFAs as bone graft materials of desired solubility can be prepared by manipulating the relative concentrations of CO(3) and F incorporated in the apatite.

Synergistic Effects of Magnesium and Carbonate on Properties of Biological and Synthetic Apatites

Magnesium (Mg) and carbonate (CO3) are minor elements associated with enamel, dentin and bone apatite. The purpose of this study was to determine the effect of Mg and CO3 on some properties of synthetic apatites to gain insights on their effects on biological apatites. Biological apatites from human enamel and dentin and from bovine bone and synthetic apatites with/without Mg or CO3 were characterized using x-ray diffraction, infrared absorption, thermogravimetry and chemical analyses. Dissolution in acidic buffer was also determined. Results from this study demonstrated: (1) the synergistic effects of Mg and CO3 on reducing the crystallinity and increasing the extent of dissolution of synthetic apatites; (2) dentin and bone, compared to enamel apatite contained higher levels of Mg and CO3; had lower crystallinity and higher extent of dissolution. The lower crystallinity and higher extent of dissolution of dentin and bone compared to enamel apatite may be partly attributed to their higher Mg and CO3 concentrations.

Spectral Properties of Carbonate in Carbonate-Containing Apatites

A study of the infrared absorption spectra of carbonate — containing synthetic and biological apatites is reviewed. The implications of the results for the nature of the incorporation of the CO3 2- ion into biological apatites is discussed.

Calcium Phosphate Bioceramics: Past, Present and Future

Calcium phosphate (CaP) bioceramics in different forms (blocks, gr anules, cements, implant coatings, composite component), from different origin (natural, bi ological or synthetic) and varying composition are commercially available for use in dentistr y and medicine. This paper briefly reviews the preparation, properties and past, present and potential future appli cations of CaP. Introduction Calcium phosphate compounds are abundant in nature and in living systems. Dif ferent types of calcium phosphate (CaP) phases play dominant and significant role in bi ological systems [1]. Carbonate hydroxy apatite (CHA) of varying crystallinity (refl ecting size and perfection) and concentration of minor elements (e.g. carbonate and magnesium) constitut e the mineral phases of teeth and bones [1,2]. Fluor-carbonate apatites are found in fish enameloids [3]. While only one type of calcium phosphate (CHA) are found in normal calcifications ( e amel, dentin, cementum, bone), different types of calcium phosphates are found to co-exist in abnor mal pathological calcifications in human (e.g., kidney stones, soft tissue calcificat ions –heart, lung, joint cartilage, dental calculus) [1,4,5]. It is not surprising therefore that CaP would be considered as a potential biomaterial. What is surprising is that it was not until 1920 that t he first successful use of a calcium phosphate compound (unspecified) for bone repair was reported [6] and more than fifty years later that the first dental application of a calcium phosphate (erroneously described as ‘tricalcium phosphate’) in surgically created periodontal defects [7] and the use of dense hydroxyapatite (HA) cylinders for immediate tooth root replacement [8] were reported. C ommercialization of synthetic calcium hydroxyapatite (HA) dental and medical applications occurre d in the 1980’s, largely through the pioneering efforts of Jarcho [9], de Groot [10] and Aoki [11]. The preparation and use of apatite derived from coral, coralline HA, bovine bone were reported later [12-17]. In the Proceedings of the 8 th International Symposium on Ceramics in Medicine, the editors reported that the percentage articles relating to HA and other CaP cer amics presented between the 1st and 8 th Bioceramic conferences (from 1988 to 1995) ranged from 40 to 70% [18]. From 1995 to 2002 (Bioceramics 9 to 14), the percentage HA and CaP articles rela ting to their preparation, properties and applications averaged 50%. Most of the articles presented in Bioce rami s conferences held before 1990 focused on basic and clinical studies using HA or beta-trica lcium phosphate ( β-TCP), as blocks, granules or implant coatings. Recent articles have include d oth r CaP ceramics in addition to HA and β-TCP (Table 1), namely, biphasic calcium phosphates (BCP), unsintered apatite (calcium deficient apatite, CDA), CaP (HA or β-TCP)/polymer composites, calcium phosphate cements (CPC) consisting of mixtures of different CaP pha ses or of calcium phosphate and other calcium compounds, e.g., α-TCP, tetracalcium phosphate, (TTCP), monocalcium phosphate monohydrate, (MCPM), amorphous calcium phosphate (ACP), dicalcium phos phate dihydrate (DCPD), dicalcium phosphate anhydrous (DCPA), and octacalcium phosphate (OCP ). This paper gives a brief review of calcium phosphate ceramics the ir preparation properties, past, present and potential future applications. Key Engineering Materials Online: 2003-05-15 ISSN: 1662-9795, Vols. 240-242, pp 3-10 doi:10.4028/www.scientific.net/KEM.240-242.3

Three-dimensional finite element analyses of four designs of a high-strength silicon nitride implant.

&NA; The effects of implant shape and size on the stress distribution around high‐strength silicon nitride implants under vertical and oblique forces were determined using a three‐dimensional finite element analysis. Finite element models were designed using as a basis the serial sections of the mandible. Using Auto‐CAD software, the model simulated the placement of implants in the molar region of the left mandible. Results of the analyses demonstrated that mainly the implant root shape and the directions of bite forces influence the stress distributions in the supporting bone around each implant. Implant size is a lesser factor. The serrated implants presented a larger surface area to the bone than either the cylindrical or tapered implants, which resulted in lower compressive stress around the serrated implants. With in creasing implant diameter and length, compressive stress decreased. The mean compressive stress distribution on the serrated implants was more flat (platykurtic) than on either the cylindrical or tapered implants. Results of studies on two load directions (vertical and oblique) showed that, in either case, the compressive stress in the cortical bone around the neck of the implant was higher than in the cancellous bone along the length of the implant. The most extreme principal compressive stress was found with oblique force. This study provides the first information on the relationship between shape of the silicon nitride implant and stress on the supporting bone. (Implant Dent 2000;9:53‐60)

Mg-Substituted Tricalcium Phosphates: Formation and Properties

This study aimed to investigate the formation and properties of mag nesium (Mg)substituted tricalcium phosphate, β-TCMP, its properties and potential as biomaterial for bone repair. β-TCMPs were prepared and characterized using x-ray diffraction, FT-IR and SEM. Dissolution properties were determined in acidic buffer. β-TCMP discs were implanted in surgically created holes in femoral and tibial diaphyses of rabbits. Results demonstrated that the formation of β-TCMP and Mg incorporation in β-TCMP were dependent on reaction pH, temperature and solution Mg/Ca ratios. Sintere d β-TCMP was significantly less soluble than β-TCP. Implanted unsintered β-TCMP showed osteoconductive properties associated with new bone formation. This study suggests that β-TCMP (sintered or unsintered), alone or in combination with other calcium phosphates, may be useful as biomaterials for bone repair and maybe useful in cases where s low r biodegradation than that of β-TCP is desired.