ECM-mimetic silk fibroin/GelMA hydrogel integrating manganese dioxide nanozymes and sustained nitric oxide release for sequential immunomodulation and healing of chronic infected wounds.

BACKGROUND

Chronic infected diabetic wounds are difficult to heal because bacterial colonisation, oxidative stress, hypoxia, and prolonged inflammation disrupt normal repair. This study developed a multifunctional extracellular matrix (ECM)-mimetic hydrogel to control infection, regulate the wound microenvironment, and promote tissue regeneration.

METHODS

A photocrosslinked silk fibroin/gelatine methacryloyl (SF/GelMA) hydrogel incorporating hollow δ-MnO₂ nanozymes and the nitric oxide donor S-nitrosoglutathione (GSNO) was developed as the NO-GSNO@MnO₂/SF-GelMA platform. Physicochemical, mechanical, nitric oxide release, oxygen generation, and antibacterial properties were characterised. Cytocompatibility, intracellular ROS scavenging, macrophage polarisation, endothelial tube formation, and angiogenesis were evaluated. Therapeutic efficacy was assessed in an MRSA-infected diabetic full-thickness wound model.

RESULTS

The hydrogel formed a stable porous network with improved mechanical properties and biocompatibility. Under acidic conditions, it provided controlled nitric oxide release, while MnO₂ nanozymes converted hydrogen peroxide into oxygen, reducing oxidative stress and hypoxia. The platform showed potent antibacterial activity against Escherichia coli and methicillin-resistant Staphylococcus aureus (MRSA), promoted M2 macrophage polarisation, enhanced endothelial tube formation, and stimulated neovascularization. In vivo, it accelerated wound healing, achieving 96.8 ± 1.4% wound closure after 14 days, with improved collagen remodelling, reduced inflammation, and enhanced vascular maturation.

CONCLUSION

The NO-GSNO@MnO₂/SF-GelMA hydrogel integrates antimicrobial, oxygen-generating, ROS-scavenging, and immunomodulatory functions into a single platform, providing a multifunctional strategy for chronic infected diabetic wound repair.