Université Clermont Auvergne, CNRS, SIGMA Clermont, ICCF, F-63000 Clermont-Ferrand, France.
Université de Pau et des Pays de l'Adour, IPREM CNRS UMR 5254, Helioparc Pau Pyrénées, 2 Avenue de Président Angot, F-64053 Pau Cedex 9, France.
Acta Biomater. 2018 Jan;65:462-474. doi: 10.1016/j.actbio.2017.10.028. Epub 2017 Oct 21.
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(PO)(OH)) and β-TCP (Ca(PO)). The two phases present two different doping mechanisms. Incorporation into the β-TCP structure is achieved at around 700 °C thanks to a substitution mechanism leading to the Cu-doped CaCu(PO) 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 °C (CaCu(PO)(OH)O with x < 0.1). Above 1100 °C, the same interstitial mechanism leads to the formation of a Cu-rich HAp mixed-valence phase (CaCuCu(PO)(OH)O with x + y ∼ 0.5). The formation of both high-temperature Cu-doped α-TCP and Cu(PO) phases above 1100 °C induces a transformation into the Cu-rich HAp phase on cooling. The linear OCuO oxocuprate entity was confirmed by EXAFS spectroscopy, and the mixed Cu/Cu valence was evidenced by XPS analyses. Ionic releases (Cu/Cu, Ca, PO 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.
Biphasic Calcium Phosphates (BCP) are bioceramics composed of hydroxyapatite (HAp, Ca(PO)(OH)) and beta-Tricalium Phosphate (β-TCP, Ca(PO)). Because their chemical and mineral composition closely resembles that of the mineral component of bone, they are potentially interesting candidates for bone repair surgery. Doping can advantageously be used to improve their biological behaviors; however, it is important to describe the doping mechanism of BCP thoroughly in order to fully appraise the benefit of the doping process. The present paper scrutinizes in detail the incorporation of copper cation in order to correctly interpret the behavior of the Cu-doped bioceramic in biological fluid. The understanding of the copper doping mechanism, related to doping mechanism of others 3d-metal cations, makes it possible to explain the rates and kinetic of release of the dopant in biological medium. Finally, the knowledge of the behavior of the copper doped ceramic in biological environment allowed the tuning of its cytotoxicity properties. The present study resulted on pre-treated ceramic disks which have been evaluated as promising biocompatible ceramic for bone substitute and/or prosthesis coating: good adherence of bone marrow cells with good cell viability.
本研究深入探讨了双相磷酸钙（BCP）的铜掺杂机制及其离子释放行为，以阐明这些生物陶瓷的细胞毒性特征。BCP 由羟基磷灰石（Ca(PO)(OH)）和 β-磷酸三钙（β-TCP，Ca(PO)）组成。这两种相具有两种不同的掺杂机制。在大约 700°C 时，通过取代机制将铜掺入 β-TCP 结构中，从而形成 Cu 掺杂的 CaCu(PO)化合物。在 HAp 结构中的掺入是通过间隙机制实现的，该机制仅限于温度低于 1100°C 的贫铜 HAp 相（CaCu(PO)(OH)O，其中 x < 0.1）。在 1100°C 以上，相同的间隙机制导致形成富 Cu 的 HAp 混合价相（CaCuCu(PO)(OH)O，其中 x + y ≈ 0.5）。在 1100°C 以上，高温下形成的 Cu 掺杂的 α-TCP 和 Cu(PO)相在冷却时会转化为富 Cu 的 HAp 相。通过 EXAFS 光谱证实了线性 OCuO 氧铜酸盐实体，并且通过 XPS 分析证明了混合 Cu/Cu 价态。在水和模拟体液中对合成陶瓷进行了离子释放（Cu/Cu、Ca、PO 和 OH）研究，以建立生物应用前的预处理。最后，评估了预处理磁盘的细胞毒性，结果证实，Cu 掺杂的 BCP 样品是有前途的骨替代物和/或假体涂层的生物陶瓷。
双相磷酸钙（BCP）是由羟基磷灰石（HAp，Ca(PO)(OH)）和 β-磷酸三钙（β-TCP，Ca(PO)）组成的生物陶瓷。由于它们的化学成分和矿物组成与骨的矿物质成分非常相似，因此它们是骨修复手术的潜在候选材料。掺杂可以有利地用于改善其生物学行为；然而，为了充分评估掺杂过程的益处，彻底描述 BCP 的掺杂机制非常重要。本文详细研究了铜阳离子的掺入，以便正确解释掺杂生物陶瓷在生物流体中的行为。对铜掺杂机制的理解，与其他 3d 金属阳离子的掺杂机制有关，使得可以解释掺杂剂在生物介质中的释放速率和动力学。最后，了解了铜掺杂陶瓷在生物环境中的行为，从而可以调整其细胞毒性特性。本研究结果是对预处理陶瓷盘的评估，这些陶瓷盘已被评估为有前途的骨替代物和/或假体涂层的生物相容性陶瓷：骨髓细胞的粘附性良好，细胞活力良好。
