H-silicene nanosheets as a novel therapeutic approach for disuse muscle atrophy by modulating macrophage polarization.

Disuse muscle atrophy (DMA) is characterized by progressive loss of muscle mass and strength, often accompanied by inflammation and macrophage imbalance. Here, we introduce hydrogenated silicene nanosheets (H-silicene) as a novel nanotherapeutic strategy to mitigate DMA through modulating macrophage polarization. H-silicene exhibited good biocompatibility and sustained hydrogen release. In vitro, H-silicene suppressed LPS-induced M1 macrophage activation while promoting M2 polarization, and alleviated myotube atrophy in co-culture assays. In a murine immobilization model, intramuscular H-silicene administration significantly mitigated muscle wasting, reduced fibrosis, and improved functional outcomes. Immunofluorescence staining confirmed a decrease in iNOS Methods: H-silicene nanosheets were synthesized from CaSi Results: H-silicene exhibited low cytotoxicity and dose-dependently suppressed LPS-induced M1 polarization while enhancing M2 polarization. It reduced proinflammatory cytokines and preserved C2C12 myotube morphology in co-culture models. In vivo, H-silicene improved muscle fiber area, reduced collagen deposition, restored grip strength , and improved rotarod performance in DMA mice. Immunostaining confirmed reduced iNOS Conclusion: This study demonstrates that H-silicene alleviates disuse-induced muscle atrophy by promoting the transition from pro-inflammatory M1 macrophages to anti-inflammatory M2 macrophages and remodeling the local immune microenvironment, making it a promising nanotherapeutic for muscle-wasting disorders.