Effect of Ag-doped hydroxyapatite as a bone filler for inflamed bone defects

Silver (Ag)-doped hydroxyapatite (HAp) agglomerates containing 0.15%, 1.5% and 4.3% mole % of silver among total cations, respectively, were evaluated in vitro and in vivo to explore their potential application as a bone filler with antibacterial properties. The 0.15% Ag-doped HAp was mildly cytotoxic, whereas the 1.5% and 4.3% Ag-doped HAps were moderately cytotoxic in the standard agar overlay cytotoxicity assay. The in vivo test was carried out by implanting Ag-HAps in artificial,bone defects at the periapical area of both mandibular 1(st) molar of rats and no remarkable cytotoxicity was found unlike what was observed in the in vitro data. All of the implanted Ag-doped HAp particles, regardless of their Ag contents, allowed appropriated cellular proliferation and favorable bone repair without remarkable inflammatory reaction through 3 week healing periods, in spite of the mild delay in organization of fibrin and inflammatory reaction with the 4.3% Ag-doped HAp at the early healing phase. They supported well new bone formation with osteointegrative and osteoconductive properties. The results suggest that HAps doped with Ag up to 4.3% of total cations can be applied for repair of infection-associated bony defects.