Calcium phosphate grafting materials are typically thought of as generic, commodity materials. However, their chemistry and physical properties are highly complex and have significant implications for their biological functioning.

All calcium phosphates are calcium salts of phosphoric acid meaning they are made by reacting an acid (phosphoric acid) with a base (calcium compound). The most common calcium phosphate is a mineral; apatite; which is an ionic crystalline material that is found in natural geological deposits. Apatites are the only water stable calcium phosphate salts. Since bone is formed in a water based environment it is no surprise that the mineral portion of bone is an apatite mineral (hydroxyapatite, HA). When apatites crystalize they incorporate not only calcium, but also a wide variety of other metals in various combinations and ratios. Body fluids are rich in trace minerals, so bone apatite is not a pure calcium phosphate either, it incorporates traces of other metals including magnesium, zinc, strontium, silicon, etc., as well as counter ions to the “free” metals other than hydroxide; fluorine and carbonate being the most common.

The trace ion profile of hydroxyapatite can have significant effects on its physical and biological properties. One of the most obvious is the substitution of fluorine for hydroxide. Teeth are made of hydroxyapatite and fluoride treatment reduces the solubility of the apatite significantly enough to practically eliminate cavity formation.

Other ionic substitutions such as carbonate for phosphate or hydroxide, or other metals for calcium, are generally regarded as being more favorable to bone growth. The reasons are not fully understood but one theory is that since bone apatite naturally incorporates these ions from body fluids, bone forming cells evolved with these substituted apatites so that similar ion profiles in synthetic materials will make them more acceptable to the body. Another reason might be that foreign ions disrupt the apatite crystal structure so that it dissolves (remodels) more readily. It is also possible that foreign ions help the apatite to better bind proteins that are involved in the bone formation process.

Synthetic apatite is usually sintered, meaning it is heated to a high temperature (around 1100⁰C) so that the individual apatite crystals fuse, grow larger, and interlock, providing mechanical strength. Without sintering, apatite is just a hard to handle micron sized powder. Sintering allows apatite to be made into useful forms such as simulated, ground cancellous bone, for example. However, natural bone is obviously not sintered. Its strength comes from a networked collagen substrate that carries the micron sized apatite crystals. Thus, the micro structure of synthetic apatite is much different from bone; synthetic apatite is a fused, relatively low porosity structure while bone is a highly porous composite of collagen and micro apatite crystals. So specifying synthetic hydroxyapatite (HA) as a bone grafting material because bone contains hydroxyapatite is not the best solution even though it initially appears logical.

Actually, synthetic calcium phosphates other than HA are better bone grafting materials. For example, tricalcium phosphate (TCP) has now become the most widely used synthetic calcium phosphate graft material. TCP is very similar to HA except that TCP is not stable in water. Thus, after implantation, the surface of a TCP graft soon transforms to water stable HA. The newly formed apatite surface is biological apatite, such as is naturally found in bone, and results in a more biocompatible graft.

This is just one example of a calcium phosphate application. The possibilities for customization are virtually unlimited; such as modifying micro-porosity and/or surface properties, incorporating different trace element profiles, changing the sintering conditions, or even producing self-setting calcium phosphate cements based on the metastable materials alpha TCP or tetracalcium phosphate. These variations can, for example, affect the graft remodeling rate, the initial healing rate, the resistance of the graft to dissolution in the presence of inflammation, the suitability of the graft as a carrier for added stem cells, peptides or proteins, the suitability of the graft for incorporation into composite materials with polymers or collagen, and the graft surgical handling properties.