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Biomaterials are synthetic compounds and composites that replace or assist missing or damaged tissue or organs. This review paper addresses Ca phosphate biomaterials that are used as aids to or substitutes for bones and teeth. The viewpoint taken is that of mineralogists and geochemists interested in (carbonated) hydroxylapatite, its range of compositions, the conditions under which it can be synthesized, and how it is used as a biomaterial either alone or in a composite. Somewhat counter-intuitively, the goal of most medical or materials science researchers in this field is to emulate the properties of bone and tooth, rather than the hierarchically complex materials themselves. The absence of a directive to mimic biological reality has permitted the development of a remarkable range of approaches to apatite synthesis and post-synthesis processing. Multiple means of synthesis are described from low-temperature aqueous precipitation, sol-gel processes, and mechanosynthesis to high-temperature solid-state reactions and sintering up to 1000 °C. The application of multiple analytical techniques to characterize these apatitic, frequently nanocrystalline materials is discussed. An online supplement 1 details the specific physical and chemical forms in which synthetic apatite and related Ca phosphate phases are used in biomaterials. The implications from this overview are the enhanced recognition of the structurally and chemically accommodating nature of the apatite phase, insight into the effects of synthesis techniques on the specific properties of minerals (specifically apatite), and the importance of surface chemistry of apatite nanocrystals. The wide range of synthesis techniques, types of analytical characterization, and applications to human health associated with apatite are a non-geological demonstration of the power of mineralogy.

Confirmation of structural H2O in apatites using 2H solid state NMR spectroscopy has been followed by the determination of the number of molecules of H2O per unit cell (MPUC) using thermal gravimetric analysis (TGA) in 10 series of carbonated apatites [CMApX; M10(PO4)6X2 = MApX] containing the divalent cations (M) calcium, strontium, barium, and lead, and monovalent anions (X) OH−, F−, and Cl−. For many of the series, the average MPUC ranges from ca. 1.5–2.5 and is independent of the concentration (wt%) of carbonate. For other series, the average MPUC is as low as ca. 0.8 or as high as ca. 4.0. We have found for six of the series, i.e., those in which carbonate predominantly (>90%) substitutes for phosphate that the average MPUC correlates with cation and anion atomic radii, with unit-cell axial lengths, and, especially, with our calculations of the void space available in the c -axis channels. We speculate that the volume of the channels in apatites affects the ability of H2O to occupy channel sites. In most low-temperature apatites of the type M10(PO4)6X2 that have been studied, carbonate prefers to substitute for phosphate (B-type substitution) rather than for monovalent anions in channel sites (A-type substitution), although computer simulations indicate that carbonate is more thermodynamically stable in the channel sites rather than the phosphate sites. In apatites with nearly total B-type carbonate substitution, there is no relationship between the number of molecules of H2O in the channels and the weight percent carbonate in the apatite. This lack of correlation would be expected when there is no competition within the channel between H2O and carbonate occupancy. In apatites with greater channel volumes, however, we infer that increased ease of carbonate incorporation in the channels also increases competition between H2O and carbonate. The originally incorporated amount of H2O is diminished to accommodate the thermodynamically favored carbonate ion substitution in the channels. We further speculate that these scenarios are most easily rationalized by incorporation of H2O early in the formation of nascent crystallites of apatites formed in aqueous solution, with carbonate entering the newly formed channels later and, in some cases, with difficulty.

Substitution of carbonate has long been recognized in both synthetic and natural biologically and geologically precipitated forms of hydroxylapatite. Although the predominant substitution mechanism in all of the calcium members of the apatite group formed below 100 °C is substitution of carbonate for phosphate (B-type), small amounts of A-type substitution of carbonate in the channel sites also occur. The present study focuses on the effect of cation size on the type of substitution of carbonate in members of the apatite group. The barium and lead members offer a larger channel site, which potentially could stabilize A-type substitution. A series of carbonated barium and lead fluorapatites were synthesized in aqueous solution and characterized by powder X-ray diffraction, and infrared and Raman spectroscopy. Carbonate content was determined by combustion analysis. Unit-cell parameters derived from X-ray diffraction showed that, as carbonate content increased, the a -axis length decreased and the c -axis increased slightly for carbonated barium fluorapatites (CBaApF), whereas the lengths of both the a - and c -axes increased for CPbApF. The co-occurrence of two sets of peaks in the ν3 carbonate region of the infrared spectra of lead and barium carbonated apatites are strongly suggestive of both A- and B-type carbonate substitution. This interpretation is supported by Rietveld analysis of X-ray powder diffraction data, which confirms the presence of significant, but not dominant, A-type substituted carbonate ions. The variation in cell parameters as a function of carbonate substitution mode is discussed, and it is shown that B-type carbonate substitution need not be accompanied by a decrease in the a -axis in all apatites. The greater amount of A-type carbonate substitution in barium and lead fluorapatites compared to the their calcium homologs can be attributed to: (1) the less negative enthalpies of hydration of the barium and lead ions relative to that of calcium, and/or (2) the greater amount of space available for the relatively large carbonate ions in the channels defined by these large cations. Thus, the substitution modes can be controlled by either thermodynamic or kinetic considerations.

Carbonate-substituted hydroxylapatite is the inorganic component in bone. The nanometer size of bone crystallites and their interweaving with subequal volumes of collagen fibrils make the chemical analysis of the bone mineral extremely difficult. The few chemical analyses that are available commonly were made on ashed bone, which, in addition to mineral, also includes chemical residues of collagen. For the present study, we chose the rostrum of the whale Mesoplodon densirostris. Its mineral content of up to 96 wt% makes it an ideal material for pursuing the chemistry of bioapatite within bone. Both bulk (X-ray fluorescence, thermogravimetry, and carbon analysis) and point analyses and element mapping (electron microprobe) were applied to this densest of bone materials. Its bioapatite has an average carbonate content of ~8 wt% and an average Ca/P atomic ratio of 1.7. The rostrum shows extremely low-concentration trace elements (Al, Si, Fe, Ti and Sr) and some minor elements (K and Cl) as in typical bone materials. Homogeneity of elemental distribution is demonstrated in typical mineral-dominated areas within the rostrum sections except around a few vascular holes and vessels. The very good correlation between electron microprobe point analyses and the XRF bulk analyses of the rostrum indicate the latter to be a useful chemical model of bone mineral. The bulk analysis shows that the bioapatite in the rostrum has an average composition of (Ca8.40Mg0.20Na0.54)[(PO4)4.87(CO3)1.13] (OH)0.87.

Despite numerous analytical studies, the exact nature of the mineral component of bone is not yet totally defined, even though it is recognized as a type of carbonated hydroxylapatite. The present study addresses the hydration state of bone mineral through Raman spectroscopic and thermogravimetric analysis of 56 samples of carbonated apatite containing from 1 to 17 wt% CO 3 , synthesized in H 2 O or D 2 O. Focus is on the relation between the concentration of molecular water (as distinguished from hydroxyl ions) and the concentration of carbonate in the apatite. Raman spectra confirm the presence of molecular water as part of the crystalline structure in all the aqueously precipitated carbonated apatites. TGA results quantitatively document that, regardless of the concentration of carbonate in the structure, all hydroxylapatites contain ~3 wt% of structurally incorporated water in addition to multiple wt% adsorbed water. We spectroscopically confirmed that natural bone mineral also contains structurally incorporated molecular H 2 O based on independent analyses of bone by means of spectral stripping (subtracting the spectrum of collagen from that of bone) and chemical stripping (chemically removing the collagen content of bone prior to analysis). Taken together, the above data support a model in which water molecules densely populate the apatite channels regardless of the abundance of hydroxyl vacancies. We hypothesize that water molecules keep the apatite channels stable even when 80% of the hydroxyl sites are vacant (typical in bone), hinder carbonate ions from substituting for hydroxyl ions in the channels, and help regulate chemical access to the channels (e.g., ion exchange, entry of small molecules). Our results show that bone apatite is not a “flawed hydroxylapatite,” but instead a definable mineralogical entity, a combined hydrated-hydroxylated calcium phosphate phase of the form Ca 10−x [(PO 4 ) 6−x (CO 3 ) x ](OH) 2−x ·nH 2 O, where n ~ 1.5. Water is therefore not an accidental, but rather an essential, component of bone mineral and other natural and synthetic low-temperature carbonated apatite phases.

Biological apatite, i.e., the major component of teeth and bones, is a widely available source of nanocrystalline apatite. More information is needed about its chemical reactivity in the environment. In the present study, wafers of cross-sectioned dentin and enamel from a modern horse tooth were soaked in phosphate-buffered solutions with NaF concentrations ranging from 0.01 to 2 molar for periods of up to 14 days at about 19.5 °C. The samples were removed at intervals and analyzed by Raman microprobe spectroscopy. Additional, real-time, in-situ Raman spectroscopic analyses were made on some samples during their fluoridation reaction, using an immersible probe. All spectra were deconvolved and their spectral components analyzed for band position, width, and area. Spectral modeling indicates that fluoridation occurred by a kinetically controlled dissolution-reprecipitation process—bioapatite grains partially dissolved and released Ca and P to the F-bearing solution, which caused essentially end-member fluorapatite to nucleate and precipitate, gradually replacing some of the original bioapatite. The replacement process, i.e., fluoridation of the sample, progresses due to the difference in solubility between bioapatite and (highly insoluble) fluorapatite. The bioapatite in (more soluble) dentin reacted much faster and to a much greater extent than that in (less soluble) enamel. These results have implications for paleoenvironmental reconstruction based on the geochemistry of fossil teeth, heavy-metal remediation in soils and water through addition of phosphate phases, and the recommended methods for dental fluoridation in humans.

Medical questions surrounding the toxicity of "silica" and other silicon-containing materials introduced into the body can be answered only through use of microanalytical techniques that provide chemical and structural analyses of microscopic and submicroscopic particles. A useful approach to the study of minerals and other foreign substances associated with silicone breast implants is to use polarized-light optical microscopy to pinpoint the materials of interest in the tissue and to follow that observation with analysis by Raman spectroscopy. Silicone breast implants contain both the organic polymer silicone and particles of amorphous silica. We studied the breast tissue from six women who had silicone breast implants and from three controls who never had implants to address questions about post-implant alteration, such as to "crystalline SiO 2 ." Optical analysis of the mammary tissue sections revealed a variety of birefringent and non-birefringent, non-cellular materials. Raman spectroscopic analyses of those substances identified many similar materials in tissue from women with and without silicone implants: calcite, apatite, starch, lipid, and beta -carotene. We also spectroscopically identified silicone (only in breast tissue from patients recognized to have had ruptured implants) and paraffin (only in one sample that had been embedded in paraffin and subsequently "deparaffinized"). In tissue sections of 5 mu m thickness (standard thickness of pathology sections), it is impossible to detect optically the birefringence of quartz (or any other form of crystalline SiO 2 ), even though it may be possible to image such thin crystalline SiO 2 grains in polarized light due to light-scattering phenomena. Moreover, neither crystalline nor amorphous silica was identified by Raman spectroscopy in the tissue sections. Review of the pathology literature on such materials-based issues as silicosis and calcification revealed some misapplication of the optical microscopy term "birefringence" and misleading identifications of minerals in tissue sections. Our conclusion is that useful collaborations can be developed between (1) pathologists who observe foreign materials in tissue sections and understand the medical context of their findings and (2) mineralogists who routinely use optical, chemical, and structural analyses to characterize micrometer-sized crystalline materials and who understand materials properties.