Aesthetic Silver-Doped Octacalcium Phosphate Powders Exhibiting Both Contact Antibacterial Ability and Low Cytotoxicity.

Since the introduction of biomaterials, infection has been a serious problem in clinical operations. Although several studies have introduced hybrid materials of calcium phosphate and Ag nanoparticles (NPs) that exhibit antibacterial activity, released Ag ions and Ag NPs are highly cytotoxic and the materials require complex fabrication techniques such as laser irradiation. In this study, we introduce a simple one-pot synthesis method based on crystal-engineering techniques to prepare Ag-substituted octacalcium phosphate (OCP-Ag) powder that simultaneously exhibits antibacterial activity, little change in color, and low cytotoxicity, thereby overcoming the shortcomings of calcium phosphate as a biomaterial. We used AgNO-containing (NH)HPO aqueous solutions as reaction solutions in which Ag forms soluble complex [Ag(NH)] ions that are stable at Ag concentrations less than ∼30 mmol/L. Hydrolysis of soluble calcium phosphate in this solution led to pure OCP-Ag when the Ag concentration was less than ∼30 mmol/L. Crystallographic analysis showed that Ag substituted at the 5 PO-conjugated sites and was uniformly distributed. When the concentration of Ag in the reaction solution was varied, the Ag content of the OCP-Ag could be controlled. The obtained OCP-Ag exhibited little color change or Ag release when immersed in various media; however, it exhibited contact antibacterial ability toward resident oral bacteria. The prepared OCP-Ag showed no substantial cytotoxicity toward undifferentiated and differentiated MC3T3-E1 cells in assays. Notably, when the Ag content in OCP-Ag was optimized (Ag: ∼1 at %), it simultaneously exhibited contact antibacterial ability, little color change, and low cytotoxicity.