3D-printed bioceramic scaffolds with a Fe₃O₄/graphene oxide nanocomposite interface for hyperthermia therapy of bone tumor cells

Simultaneous therapy and regeneration of bone tumor-induced defects still remain to be a significant challenge. Conventional therapy strategy by implanting bone graft materials can regenerate the bone defects after surgery but cannot kill residual tumor cells. In this study, we successfully prepared a 3D-printed β-tricalcium phosphate bioceramic scaffold with surface modification of Fe₃O₄ nanoparticles/graphene oxide nanocomposite layers (named β-TCP-Fe-GO). The prepared β-TCP-Fe-GO scaffolds possess a highly ordered macroporous structure with triangle pore morphology and a pore size of around 300-500 μm. The struts of β-TCP-Fe-GO scaffolds were uniformly deposited with Fe₃O₄/GO sandwich-like composite layers in which nano-sized Fe₃O₄ particles were wrapped by GO sheets. The Fe₃O₄ content in the β-TCP-Fe-GO scaffolds can be effectively modulated by controlling the coating times; the final content of Fe₃O₄ in β-TCP-8Fe-GO scaffolds is no more than 1% after coating 8 times. Such low content of Fe₃O₄ in the scaffolds endows them with super paramagnetic behavior and hyperthermal effects. The temperature of the scaffolds can be modulated in the range 50-80 °C under an alternating magnetic field for 15 minutes by controlling the magnetic intensity and Fe₃O₄ content. The excellent hyperthermal effect of β-TCP-Fe-GO scaffolds induced more than 75% cell death for osteosarcoma cells (MG-63) in vitro. Furthermore, the β-TCP-Fe-GO scaffolds significantly enhanced alkaline phosphatase (ALP) activity and osteogenic gene expression, such as OPN, Runx2, OCN and BSP, of rabbit bone marrow stromal cells (rBMSCs) and significantly stimulated rBMSCs proliferation as compared to pure β-TCP scaffolds by the synergistic effect of GO and the released Fe ions. Therefore, the prepared β-TCP-Fe-GO scaffolds possess prominent magnetothermal ability and excellent bone-forming activity. This study is believed to pave the way for the design and fabrication of novel tissue engineering scaffolds in a combination of therapy and regeneration functions.