Multifunctional composite magnetic particles combined with static magnetic field for treating infectious bone defects via SLC2A1-mediated HIF-1 and PI3K/AKT pathways

Infectious bone defects are a major challenge in orthopedics and stomatology, requiring strategies that eliminate bacteria and promote osteogenesis. Here, we developed a multifunctional composite magnetic particle system (F-Fe₃O₄) and demonstrate its synergistic combination with a static magnetic field (SMF) for treating infectious bone defects. In vitro, F-Fe₃O₄ demonstrated good biocompatibility with human bone marrow-derived mesenchymal stem cells (hBMSCs) and facilitated their proliferation, migration, and osteogenic differentiation, while inhibiting the growth of Escherichia coli, Staphylococcus aureus, and Enterococcus faecalis. With the application with SMF, the aforementioned effects are further enhanced. The in vivo studies in the rat model further revealed that F-Fe₃O₄ combined with SMF can reduce early infection, alleviate inflammation, and accelerate new bone formation. Mechanistically, RNA sequencing and verification experiments revealed that the combination therapy upregulated SLC2A1-mediated glucose uptake and activated HIF-1 and PI3K/AKT signaling pathways, thereby enhancing the osteogenic differentiation of hBMSCs. In conclusion, this study developed an efficient treatment approach for infectious bone defects by integrating F-Fe₃O₄ and SMF.