Multifunctional magnetocaloric bone cement with a time-varying alkaline microenvironment for sequential bacterial inhibition, angiogenesis and osteogenesis

Abstract

Repairing infected bone defects remains a severe challenge due to antibiotic abuse and recurrence. Hence, we modified magnetocaloric Fe₃O₄ nanoparticles and added them to magnesium calcium phosphate bone cement (MCPC) to fabricate multifunctional magnetic composites for sequential bacterial inhibition, angiogenesis and osteogenesis. Nevertheless, high doses of Mg ions and Fe ions were released from MCPC, which adversely affected osteogenesis. Thus, Fe₃O₄ was modified using gelatin according to the emulsification crosslinking method, which exhibited a controllable magnetocaloric effect and degradation behavior, and favorable anti-bacterial ability under the action of an alternating magnetic field (AMF). In the early stage, the residual MgO created a local strong alkaline microenvironment by hydrolysis, which inhibited the function and activity of S. aureus and E. coli. At the later stage, the MCPC composites were controllably degraded under the function of gelatin and maintained a long-term local slight alkaline microenvironment that promoted the osteogenic differentiation and mineralization of BMSCs. In vivo subcutaneous implantation experiments further indicated that MCPC composites showed good biocompatibility and facilitated angiogenesis, presenting a promising future in magnetic materials design and infectious bone defect repair.