Injectable, antibacterial, ROS scavenging and pro-angiogenic hydrogel adhesives promote chronic wound healing in diabetes via synergistic release of NMN and Mg2+

Diabetic wound care continues a significant clinical problem due to the complex wound microenvironment characterized by excessive ROS, bacterial infection, persistent inflammation, impaired NAD+ biosynthesis, and angiopathy. Particularly, scavenging ROS, enhancing NAD+ levels and promoting angiogenesis are critical for improving diabetic wound healing. This study presents a novel in situ injectable hydrogel based on poly(glycerol sebacate)–co-poly(ethylene glycol)-g-catechol prepolymer (PEGSD) and quaternized chitosan (QCS), which is further loaded with nicotinamide mononucleotide (NMN) and Mg2+ (QP/NMN/Mg2+) and catalytically cross-linked by a mild horseradish peroxidase (HRP)/H2O2 system for type II diabetic wound healing. The hydrogel shows multifunctional properties including excellent biocompatibility, tissue adhesion, rapid hemostasis, antibacterial activity, ROS scavenging and angiogenesis promotion. The electrostatic and coordination interactions ensure the prolonged release of NMN and Mg2+. Specifically, as an NAD+ precursor, the addition of NMN further alleviates oxidative stress and rescues angiogenic capacity. Moreover, the presence of Mg2+ enhances the antibacterial activity of hydrogel against S. aureus. The results demonstrate the synergy of NMN and Mg2+ in hydrogel significantly promotes HUVEC proliferation and tube formation, fibroblast migration, and greatly accelerates diabetic wound healing, presenting a feasible strategy for chronic diabetic wound repair.