Multi-functional nanozyme-integrated astragalus polysaccharide hydrogel for targeted phased therapy in diabetic wound healing

Abstract

Diabetic wounds (DW) are characterized by excessive oxidative stress, chronic inflammation, hypoxia, impaired angiogenesis, weakened antioxidant defenses, and disrupted collagen remodeling, all of which delay healing and compromise tissue integrity. To address these challenges, we developed a biodegradable multifunctional hydrogel dressing (Fe/Ce@APS Gel) comprised of astragalus polysaccharide (APS), polyvinyl alcohol (PVA), and borax, functionalized with multi-enzyme mimetic nanozyme iron-modified ceria nanoparticles (Fe/CeNP-PEG). This Fe/Ce@APS Gel demonstrates potent anti-inflammatory, antioxidant, oxygenation, and pro-angiogenic properties, supporting wound healing across all stages. In the initial bleeding phase, the dressing accelerates blood clotting, promoting rapid wound stabilization. During the inflammatory phage, Fe/CeNP-PEG and APS effectively reduces excess reactive oxygen species (ROS) generates oxygen, modulates macrophage polarization, and mitigates inflammatory responses. In the proliferative phase, APS enhances cell proliferation, stimulates angiogenesis, and accelerates granulation tissue formation, supporting tissue repair. Finally, in the remodeling phase, Fe/Ce@APS Gel aids in tissue architecture reconstruction, strengthening wound integrity. Mechanistically, Fe/Ce@APS Gel facilitates DW healing by inhibiting the NLRP3/NF-κB signaling pathway, thereby reducing inflammation. The synergistic effects of APS and Fe/CeNP-PEG underscore the potential of Fe/Ce@APS Gel as a promising therapeutic dressing for DW treatment.