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

Sugiura, Yuki; Obika, Hideki; Horie, Masanori; Niitsu, Kodai; Makita, Yoji

[Image: see text] 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 P5 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.