Fluorine substituted hydroxyapatite microspheres: Template-free hydrothermal synthesis and sustained fluoride-releasing properties

To avoid sudden release of fluoride, F-substituted hydroxyapatite (FHA) porous microspheres were prepared for the treatment of F-deficiency tissues. In the absence of any template-directing reagents, FHA microspheres with diameters of about 30 ?m were successfully fabricated via hydrothermal method with urea as homogeneous precipitant to regulate the nucleation, growth and self-assembly process. Urea concentration and hydrothermal temperature played an important role in the formation and regulation of spherical hydroxyapatite. The synthesized FHA microspheres with large specific surface area, large pore volume and complex porous structure were efficient for the adsorption and long-term stable release of ionic extracts. Concentration of F- ions in physiological salt solution was maintained in the range of the therapeutic window without exceeding the toxic threshold within 30 days. The ionic extracts of FHA porous microspheres promoted the proliferation of human osteoblast-like cells (MG-63). The fabricated FHA microspheres may be a potential candidate as bioactive fluoride-release carriers for the treatment of osteoporosis and bone defects.