A smart CO-releasing MnSiO3-based hydrogel enhances diabetic wound healing through NIR-triggered antibacterial, anti-inflammatory, and pro-regenerative mechanisms

Diabetes is a growing global health concern often associated with chronic wounds characterized by persistent infection, excessive inflammation, and impaired angiogenesis. To address these challenges, we developed a multifunctional hydrogel MnSiO₃-Fe₃(CO)₁₂/ICG@PF127 (MF/ICG@PF127) that combines photothermal and photodynamic antibacterial effects, controlled carbon monoxide (CO) release, and immunomodulatory activity to promote diabetic wound healing. This hydrogel was constructed by encapsulating Fe₃(CO)₁₂ within MnSiO₃ nanoparticles (MF) and co-assembling with indocyanine green (ICG) into a thermosensitive Pluronic F127 matrix (Poly(ethylene oxide)-block-poly(propylene oxide)-block-poly(ethylene oxide)), forming a near-infrared (NIR)-responsive platform. In vitro, MF/ICG@PF127 exhibited excellent biocompatibility, potent antibacterial activity under NIR irradiation, and effective suppression of inflammatory cytokines (IL-6, iNOS, IL-1β). It also enhanced fibroblast and endothelial cell migration and tube formation. In vivo, NIR-activated MF/ICG@PF127 significantly accelerated wound closure and tissue regeneration in diabetic mice. Immunofluorescence showed enhanced M2 macrophage polarization and reduced inflammation. Transcriptomic analysis revealed activation of the Wnt/β-catenin signaling pathway and upregulation of angiogenic (VEGFR2) and proliferative markers (Cyclin D1, c-Myc). These synergistic effects highlight MF/ICG@PF127 hydrogel as a promising strategy for remodeling the diabetic wound microenvironment and facilitating chronic wound repair.