A multifunctional self-initiated photo-crosslinking insect chitosan hydrogel loaded with ZIF-8@Ga-EGCG for promoting healing of MRSA-infected diabetic wounds

Diabetic wounds represent one of the most prevalent complications in patients with diabetes mellitus. Elevated reactive oxygen species (ROS), bacterial infections, persistent inflammation, and impaired angiogenesis collectively contribute to delayed diabetic wound healing. In this study, a multifunctional, injectable, photoinitiator-free, photocrosslinkable hydrogel (G/Z@M) based on insect-derived chitosan was developed. The hydrogel system incorporated lipoic acid (LA), which possesses photopolymerization capability and potent antioxidant activity, to modify quaternized chitosan (QMCS). Through self-initiated photo-crosslinking of QMCS-LA, the hydrogel's three-dimensional network was constructed. Simultaneously, the ZIF-8@MPN nanocomposite was constructed by coating ZIF-8 with a metal-polyphenol network (MPN) functional coating formed through the coordination of epigallocatechin gallate (EGCG) with Ga 3+ . This nanocomposite was then loaded onto the QMCS-LA network. Both in vitro and in vivo experiments demonstrated that the G/Z@M hydrogel possesses great biocompatibility, antibacterial, anti-inflammatory, antioxidant, and pro-angiogenic activities, effectively promoting the healing of full-thickness skin defect wounds in MRSA-infected diabetic rats. In conclusion, the G/Z@M hydrogel presents an innovative therapeutic approach for diabetic infected wounds by simultaneously regulating oxidative stress, bacterial infection, persistent inflammation, and impaired angiogenesis.