Environmentally activatable hydrogel for spatiotemporally programmed nitric oxide delivery for diabetic wound healing

Nitric oxide (NO) plays a central role in wound healing, by regulating vascular homeostasis, inflammation, and antimicrobial effects. However, chronic diabetic wounds are difficult to heal due to the hyperglycemic microenvironment, which reduces endogenous NO production. Therefore, developing intelligent dressings capable of spatiotemporally programmed NO delivery holds great promise in promoting diabetic wound healing. Herein, we engineered an environmentally activatable hydrogel that enabled on-demand NO release for diabetic wound healing. The CS-SNAP hydrogel was achieved by covalent grafting of NO donor (S-nitroso-N-acetylpenicillamine, SNAP) onto the matrix of carboxymethyl chitosan methacryloyl (CMCSMA), and by subsequent fast photopolymerization during only 10 s. The CS-SNAP hydrogel enabled sustained release of NO over 300 min by simply modulating ambient light and temperature. When applied to diabetic wounds, not only did the CS-SNAP hydrogel exhibit effective antibacterial activity, but it also showed good angiogenic ability and promoted M1-to-M2 polarization of macrophages. Together, this environmentally activatable platform demonstrates great potential to shorten the inflammatory phase of diabetic wounds, prevent bacterial colonization, and accelerates diabetic wound healing.