Zinc-containing tricalcium phosphate and related materials for promoting bone formation

Abstract

Calcium phosphate is a suitable carrier of zinc, an essential element that has stimulatory effects on bone formation in vitro and in vivo as well as an inhibitory effect on osteoclastic bone resorption in vitro. The highest zinc content is attained in β-tricalcium phosphate, where the zinc content reaches 6 wt%. Both rat and human bone marrow cells (BMCs) cultured on zinc-containing β-tricalcium phosphate and hydroxyapatite composite ceramics differentiated more than BMCs cultured on zinc-free composite ceramics in the presence of β-glycerophosphate and dexamethasone. The acceptable dose of zinc was higher for human BMCs than for rat BMCs. The solubility of ZnTCP, which contains a nontoxic level of zinc, decreased to 52–92% that of pure TCP in the pH range of 5.0–7.4. However, the resorbed volume of ZnTCP was much lower than that expected from the in vitro solubility of ZnTCP, becoming as low as 26–20% that of TCP, which indicates that the reduction in the resorbability of ZnTCP would be attributable principally to its lowered cellular activation property relative to that associated with pure TCP. Probably due to the lowered cellular activation property associated with ZnTCP, bone loss at the bone-implant interface was significantly arrested in the long-term implantation of ZnTCP/HAP. The intramuscular injection of ZnTCP powder is effective in increasing bone mineral density in the vicinity of the injected site in osteopenic animals. All these findings suggest that zinc-containing calcium phosphate is a biomaterial that promotes bone formation.