Mineralization Pathways of Amorphous Calcium Phosphate in the Presence of Fluoride

Amorphous calcium phosphate (ACP) has been widely reported as a metastable precursor during the mineralization of calcium phosphates in bone and enamel. Although the influence of fluoride on the crystallization of hydroxyapatite (HAP) has been extensively investigated, the mineralization pathways of ACP in the presence of fluoride are not fully understood. Here, using a combination of in situ monitoring and ex situ characterizations, we show that fluoride exhibits little effect on the formation and particle size of ACP nanospheres from a supersaturated calcium phosphate solution. However, the stability of ACP increases with increasing concentration of free fluoride ions in solution. We show that the aggregation of ACP nanospheres into larger spheres is an important step during ACP crystallization, which drives the nucleation of plate-like nanocrystals on the surface of ACP nanospheres and induces subsequent crystallization of ACP via a dissolution-recrystallization pathway. In the presence of fluoride, the aggregation of ACP nanospheres and the nucleation of crystalline phases are retarded, thus stabilizing the amorphous phase. In addition, fluoride promotes the formation rod-like crystals on the surface of ACP nanospheres, which grow both outward from solution ions and inward from ACP nanospheres. These results significantly improve our understanding of the mineralization pathways of ACP and explain the inhibitory effect of fluoride during ACP crystallization.