A GelMA hydrogel co-loaded with resveratrol, 18-β-glycyrrhetinic acid, and berberine for the combination therapy of infected wounds

OBJECTIVES: To develop a gelatin methacrylate hydrogel dressing loaded with traditional Chinese medicine active components-resveratrol (RES), 18-β-glycyrrhetinic acid (GA), and berberine (BBR)-for the treatment of infected wounds, aiming to enhance wound healing through their anti-inflammatory, antibacterial, and antioxidant properties. METHODS: Methacrylamidated gelatin was synthesized from gelatin and methacrylic anhydride and used to load RES, GA, and BBR. The wound-healing and anti-infective effects were evaluated in a mouse model with full-thickness dorsal skin defects. Histological evaluation was performed via hematoxylin and eosin staining to assess re-epithelialization and hair follicle regeneration. KEY FINDINGS: Gelatin methacrylate hydrogel dressings loaded with RES, 18-GA, or BBR alone showed therapeutic effects in clearing infection and promoting healing. Gelatin methacrylate hydrogel dressings co-loaded with RES, GA, and BBR achieved a wound closure rate of 77.92% by Day 12. The triple-loaded dressing demonstrated higher infection clearance, more continuous epidermis, and increased hair follicle regeneration compared with single-component dressings. CONCLUSIONS: Gelatin methacrylate hydrogel dressings co-loaded with RES, GA, and BBR exhibit superior potential in promoting the healing of infected wounds, as evidenced by enhanced wound closure, infection clearance, and skin structure regeneration in vivo.