Synergic Effect of Sr2+ and Mg2+ on the Stabilization of Amorphous Calcium Phosphate

Amorphous calcium phosphate (ACP) is a metastable precursor phase for bone formation, and it can transform into the thermodynamic stable mineral phase, hydroxyapatite (HAP, the main inorganic phase in bone), under physiological conditions. In a biological system, it has been documented that Mg2+ can effectively stabilize ACP to ensure a regulation of biomineralization kinetics. In this study, we investigate the effect of another alkaline earth metal ion, Sr2+, on ACP stabilization. Although Sr2+ plays an important role in bone formation, its mechanism is poorly understood. We find that Sr2+ itself has less stabilization effect on ACP in comparison with Mg2+. However, the presence of Sr2+ can significantly enhance the stabilization of Mg2+ on ACP due to a synergic effect. The chemical analysis reveals more Mg2+ should be excluded from ACP to initiate the crystallization of HAP when Sr2+ ions coexist in the amorphous phase. This change results in additional energy barriers for the solid phase transformation to provide a better stabilization effect on ACP, which benefit bone formation. This finding highlights the process of dopant ion exclusion in ACP and its control, which enriches our understanding on the bioinspired regulation of crystallization by using the cooperation of multiple ions.