Good hydration and cell-biological performances of superparamagnetic calcium phosphate cement with concentration-dependent osteogenesis and angiogenesis induced by ferric iron

The multifunctionality of calcium phosphate cement (CPC) can be achieved via co-doping with different metallic ions. Magnetism and hyperthermia have been proposed as potential therapeutic methods in bone healing and anti-osteosarcoma treatment. Iron-doping in biomaterials has been confirmed to meet the clinical requirements for these treatments. Herein, superparamagnetic iron-doped CPC (Fe-CPC) showed improved injectability and compressive strength, increased negative surface charge and accelerated hydration with increasing Fe3+ concentration. The superparamagnetism of Fe-CPC was confirmed through vibrating sample magnetometer (VSM) analysis. Mouse bone marrow stromal cells (mBMSCs) cultured on Fe-CPC disks exhibited better attachment morphology and proliferation, and had an enhancement of osteogenic-related gene expression. Moreover, a series of extracts with different concentrations of Fe3+ in cell culture medium were leaching-prepared to simulate the Fe3+-containing liquid environment around the magnetic biomaterials. The performances of mBMSCs and human umbilical vein endothelial cells (HUVECs) cultured in Fe3+-extracts showed increased proliferation rate in a certain amount of Fe3+. Osteogenesis and angiogenesis induced by Fe3+ were observed, but cytotoxicity in mBMSCs appeared when the concentration of Fe3+ was beyond a critical value. Fe-CPC is supposed to have prospective applications in bone remodeling through the combination of self-setting in situ, injectability, superparamagnetism, osteogenesis, angiogenesis, and osteoconductivity.