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

Abstract 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-Fe 3 O 4 ) and demonstrate its synergistic combination with a static magnetic field (SMF) for treating infectious bone defects. In vitro, F-Fe 3 O 4 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-Fe 3 O 4 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-Fe 3 O 4 and SMF.