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 0 nanoparticles (NPs) that exhibit antibacterial activity, released Ag + ions and Ag 0 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 3 -containing (NH 4 ) 2 HPO 4 aqueous solutions as reaction solutions in which Ag + forms soluble complex [Ag(NH 3 ) 2 ] + 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 P 5 PO 4 -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.