Fluorine-substituted hydroxyapatite (FHA) has attracted much attention and increasingly investigated as clinical restoration materials in recent years due to the extensive findings of partially fluoridated hydroxyapatite in bone and teeth and, also, favorable effect of fluoride on bone ingrowth. In this study FHA powders were synthesized by solid-state reaction via mechanical alloying (MA) method and sol-gel route, with a chemical composition of Ca 10 (PO 4 ) 6 OH 2-x F x, with x = 0.0, 0.5, 1.0, 1.5 and 2.0. The MA process was done under different conditions (I-V) in order investigating the effect of MA parameters on the syntheses and characterize of produced nanopowders. The synthesized powder was characterized using X-ray diffraction (XRD), Transmission electron microscopy (TEM), Fourier transform infrared (FTIR) spectroscopy and ICP-OES analysis to evaluate phase composition, morphology and particle size, functional chemical group and purity of products, respectively. The in vitro test was performed by immersion of powders in Kokubo's SBF medium up to 4 week. The changes of pH of the SBF medium were measured at pre-determined time intervals using a pH meter. The calcium and phosphorous ions concentrations of SBF medium were determined using ICP-OES analysis. The apatite formation on the surface of the samples as consequence of the dissolution and precipitation process of calcium phosphate was investigated by scanning electron microscopy (SEM). FTIR results combined with the X-ray diffraction exhibited single phase of homogeneous FHA with carbonate peaks in the FTIR spectrum after 6 hr under the best MA conditions (condition III). TEM results showed that obtained powder after 6hr of milling under the condition III was compost of FHA nanoparticles (35-65 nm). In vitro test illustrated that dissolution rate of FHA decreased as a result of increasing fluorine content of FHA powders. Moreover the larger quantity of tiny nucleus was observed on surface of fluorapatite samples with respect to other samples. However, the quantity of precipitated bone-like apatite crystals on the surface of samples decreased as fluorine content increased.
