A smart CO-releasing MnSiO(3)-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 MnSiO(3)-Fe(3)(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 Fe(3)(CO)(12) within MnSiO(3) 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.