Development of bioresorbable porous sintered apatities as bone substitutes

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The usefulness of sintered carbonate apatites (CAp) as bone substitutes were investigated in vitro and in vivo. For in vitro evaluation, we used a rat bone marrow cell culture. In this cell culture, we also used sintered hydroxyapatite (HAp), β-tricalcium phosphate ( β-TCP), magnesium-containing β-TCP (Mgβ-TCP) and Hap(70wt%)-Mg, β-TCP(30wt%) substrates for comparison and the adhesion, proliferation, and differentiation of osteoblastic cells on these substrates including standard plastic culture plate substrates were investigated. At 7-day culture, parameters such as the number of cells adhered, DNA contents, alkaline phosphatase activity, calcium and phosphate contents originating from the calcified nodules were significantly higher with Cap substrates than with the plastic culture plate substrates. No great significant differences were noted among Hap, β-TCP, Mg β-TCP, Hap-Mg β-TCP and Cap in the parameters, though β-TCP tended to show smallest alkaline phosphatese activity with the … More number of cells being almost the same with the other calcium phosphatase activity with the number of cells being almost the same with the other calcuim phosphate substrates. At 14-day culture, the parameters with the plastic culture plate substrates tended to become close to those of the calcuim phosphate substrates including CAp substrates. Neverless, SEM micrographs clearly suggested that osteoblasitc cells appeared much more active and more proliferated on CAp, HAp, HAp-Mgβ-TCP substrates than on plastic plate, β-TCP and Mgβ-TCP substrates. For the latter three substrates, the calcium and phosphate contents of calcified nudules formed during culture were found to be smaller.For in vivo evaluation, sintered carbonate apatites in porous form with each particle size being in the range of 300-500μm (coarse particles) and less than 200μm (fine particles) were implanted in rat skull defects. Micro-focus X-ray computed tomography showed that bone hardly formed in the defects filled with no materials at least till 3 weeks after implantation but in the defects filled with the materials bone formed by two weeks. Staining of sectioned specimens by TRAP showed that there were many TRAP-positive cells around the resorbing material, suggesting that the resorption of the sintered carbonate apatite particles is, in part, similar to osteoclastic bone resorption. At 4, 6 and 8 weeks after implantation, the new bone contained osteoclastic and was a mineralized and dense as the host bone. These findings suggest that sintered carbonate apatites would be useful as bioresorbable bone substitutes. Less