Cu-doping of calcium phosphate bioceramics: From mechanism to the control of cytotoxicity

In this study, the Cu-doping mechanism of Biphasic Calcium Phosphate (BCP) was thoroughly investigated, as was its ionic release behavior, in order to elucidate cytotoxicity features of these bioceramics. BCP are. composed of hydroxyapatite (Ca-10(PO4)(6)(OH)(2)) and beta-TCP (Ca-3(PO4)(2)). The two phases present two different doping mechanisms. Incorporation into the beta-TCP structure is achieved at around 700 degrees C thanks to a substitution mechanism leading to the Cu-doped Ca3-xCux(PO4)(2) compound. Incorporation into the HAp structure is achieved thanks to an interstitial mechanism that is limited to a Cu-poor HAp phase for temperatures below 1100 degrees C (Ca10Cux(PO4)(6)(OH)(2-2x)O-2x, with x <0.1). Above 1100 degrees C, the same interstitial mechanism leads to the formation of a Cu-rich HAp mixed-valence phase (Ca10Cux2+Cuy+(PO4)(6)(OH)(2-2x-y)O2x+y with x + y similar to 0.5). The formation of both high-temperature Cu-doped alpha-TCP and Cu-3(PO4)(2) phases above 1100 degrees C induces a transformation into the Cu-rich HAp phase on cooling. The linear O-Cu-O oxocuprate entity was confirmed by EXAFS spectroscopy, and the mixed Cu+/Cu2+ valence was evidenced by XPS analyses. Ionic releases (Cu+/Cu2+, Ca2+, PO42- and OH-) in water and in simulated body media were investigated on as-synthesized ceramics to establish a pretreatment before biological applications. Finally the cytotoxicity of pretreated disks was evaluated, and results confirm that Cu-doped BCP samples are promising bioceramics for bone substitutes and/or prosthesis coatings. (C) 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.