A clinically guided photocurable hydrogel platform for antimicrobial peptide substitution in personalized wound infection therapy

The healing of infected skin wounds remains a major clinical challenge due to persistent bacterial contamination and prolonged inflammation. In this study, we report the development of a multifunctional, light-curable sodium alginate-based hydrogel by grafting antimicrobial peptides (AMPs) onto oxidized sodium alginate (OSA) via Schiff base reactions and incorporating silver nanoparticles (AgNPs). The dual-network hydrogel, formed by blending AMP@OSA with methacrylated alginate (AlgMA) and subsequent ultraviolet (UV) curing, exhibited a pH-responsive release behavior targeting the acidic microenvironment of infected wounds. In vitro studies demonstrated strong antibacterial activity against Staphylococcus aureus and Escherichia coli , significant inhibition of biofilm formation, and excellent biocompatibility, evidenced by minimal cytotoxicity and hemolysis. Treatment of a rat dorsal full-thickness infected wound model with the AMP-AgNPs@OSA hydrogel markedly accelerated wound closure, enhanced re-epithelialization, and promoted collagen deposition. Mechanistically, the hydrogel modulated the immune microenvironment by inducing macrophage polarization toward the anti-inflammatory M2 phenotype, thereby mitigating inflammatory responses and supporting tissue regeneration. These findings establish AMP-AgNPs@OSA hydrogel as a multifunctional dressing capable of simultaneously controlling infection and promoting wound repair, with strong potential for advanced clinical use in the management of infected skin defects. Moreover, the antimicrobial peptide component can be flexibly replaced with clinically appropriate antibiotics based on antimicrobial susceptibility testing, allowing personalized infection control and expanding the hydrogel’s translational relevance across diverse pathogens.