Biomimetic preparation of trace element-codoped calcium phosphate for promoting osteoporotic bone defect repair

Specific implants to speedily regenerate critical-sized osteoporotic bone defects (COBDs) are a major clinical need. However, little progress in methods focusing on biological repair has been reported. We developed a biomimetic mineralization method to prepare trace element-codoped calcium phosphate (CaP) particles via hydrothermal treatment of modified simulated body fluid (SBF) with the addition of binary to quaternary trace elements. The morphology, structure, and composition of the particles were characterized by a combination of SEM, TEM, XRD, and FTIR measurements. The quantitative analysis shows that the dopant contents in the solid phase can be regulated by the trace ion concentrations in the aqueous medium. The conditioned cell culture medium from the quaternary Mg/Zn/Sr/Si-co-doped CaP (qCaP) could significantly enhance cell activity and osteogenic differentiation of ovariectomized rat-derived bone marrow mesenchymal stem cells. After injecting the qCaP-loaded chitosan/hyaluronic acid hydrogel into the COBDs, histology and computed tomography scanning revealed that the new bone regeneration was significantly enhanced, and the quantity of mature bone was substantially increased in the rats implanted with qCaP 12 weeks post-operatively in comparison with the defects filled with the CaP obtained from SBF. These results suggest that the biomimetic mineralization of the trace ion-added SBF allows the preparation of highly bioactive trace element-codoped CaP biomaterials and these materials are potential candidates for the biological repair of COBDs.