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This study aimed at evaluating the cytotoxicity of experimental fluoride-doped hydroxy-calcium-phosphates and their bioactivity in converting them into hydroxy/fluoro‐apatite. Experimental fluoride-doped hydroxy-calcium-phosphates were formulated by using a 1:1 molar ratio of beta-tricalcium phosphate (α-TCP) and monocalcium phosphate monohydrate (MCPM), doped with calcium hydroxide (10 wt%) and calcium and sodium fluoride salts (1:1 molar ratio) at different concentration of (VSG5F%; VSG10F%; VSG20F%) (Patent: WO2019243592). A fluoride-free (VSG) hydroxy-calcium-phosphate was also formulated and used as a control material. Each powder was immersion in SBF (24 h, 2 and 4 weeks) and submitted to the following analysis to evaluate their bioactivity in inducing apatite-like formation: a) vibrational analysis FTRI-ATR; b) X-ray diffraction; c) TEM-EDX-XRD. Cumulative fluoride release (ppm) was performed for up to 2 months. Each powder was immersed in SBF for 24 h and placed into a hDPSCs (200 mg/mL) medium (ISO/EN 10993-12). Serial dilutions of extracts were prepared (1:1-to-1:200) and their cytotoxicity was analyzed using a MTT [3-(4,5- dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay (initial density of 5 ×103), (incubation 24 h, 48 h, 72 h). Cells on tissue culture plates with a medium were used as a control. The results were statistically analyzed by means of analysis of variance (ANOVA) and Tukey's multiple comparison test (α= 0.05). After 2 weeks of storage in SBF, VSG10F and VSG20F were totally converted into crystals of hydroxy/fluoro-apatite. VSG20F still presented unreacted fluoride after 4 weeks of storage, which was continuously released and accumulated in the media. All the powders showed a significant toxicity at all time points at dilution of 1:1. VSG0F and VSG20F showed a significant toxicity after 24 h (dilutions 1:5), but after 72 h a significant increase in cell proliferation was observed in all the SVGF powders. At 1:10, VSG20F showed the greatest toxicity, while at 1:20, VSG10F and VSG20F showed a reduction of cell viability of only 3% and 13% respectively (48 h). At lower dilutions (1:20, 1:100 and 1:200) no powders showed significant toxicity compared to the control, but an increase in cell proliferation was observed at 72 h with VSG5F and VSG10F. The experimental fluoride-doped hydroxy-calcium-phosphates tested in this study may be potentially used for the remineralization of dentine and enamel thanks to their ability to convert into hydroxy/fluoro‐apatite crystals. As a result of their remarkable biocompatibility and to their ability to induce cell proliferation in some specific conditions, the experimental fluoride-doped hydroxy-calcium-phosphates tested in this study could also be employed for the formulation of pulp-protection materials. [ABSTRACT FROM AUTHOR]