Magnesium Phosphate Composite Hydrogel Dressing Promotes Diabetic Wound Repair Through Anti-Inflammatory, Antioxidant, Angiogenic, and Metabolic Regulatory Mechanisms.

Abstract

Chronic non-healing diabetic wounds pose a significant clinical challenge, attributed to a pathogenic microenvironment characterized by persistent inflammation, excessive accumulation of reactive oxygen species, impaired angiogenesis, and mitochondrial dysfunction. Herein, we reported a novel multifunctional hydrogel dressing aimed at promoting diabetic wound healing through the synergistic action of anti-inflammatory, antioxidant, angiogenic, and metabolic regulatory mechanisms. First, nicotinamide mononucleotide (NMN)-templated magnesium phosphate nanoparticles (NMP NPs) were synthesized through a biomimetic mineralization strategy. Subsequently, the NMP NPs were incorporated into a double-network hydrogel that formed by dynamic Schiff base crosslinking and photocuring of methacrylated gelatin and oxidized dextran, resulting in a multifunctional composite hydrogel (NMP/GO) with tissue adhesion properties and multiple biological activities. The NMP/GO hydrogel dressing slowly releases Mg2+ ions and NMN within the diabetic microenvironment, where Mg2+ modulates inflammatory responses and promotes angiogenesis, while NMN restores redox balance and ameliorates mitochondrial dysfunction. Owing to this synergistic effect, the NMP/GO hydrogel dressing significantly promotes diabetic wound healing by reducing inflammation, mitigating oxidative stress, restoring mitochondrial function, and enhancing angiogenic potential. Consequently, the NMP/GO hydrogel dressing presents a promising therapeutic strategy for advanced diabetic wound management with high translational potential.