Carboxymethyl chitosan - sodium alginate dual-loaded drug nanofiber sheet promotes wound healing of diabetic skin

A CMCS-SA nanofiber biomembrane loaded with chlorogenic acid and astragalus polysaccharide was fabricated via electrospinning • The dual-active-loaded nanofiber biomembrane modulates oxidative stress and inflammatory response via NRF2/HO-1 signaling pathway • The nanofiber dressing accelerates diabetic wound repair by promoting collagen deposition and dermal tissue reconstruction • Natural-product-based electrospun nanofiber shows promising potential for diabetic wound healing application Background Chronic diabetic wounds are difficult to heal due to persistent oxidative stress, uncontrolled inflammation, cellular dysfunction, and impaired angiogenesis. Traditional dressings cannot actively regulate this complex microenvironment; thus, new active repair materials are urgently needed. Methods A dual-drug loaded nanofiber mat was constructed using carboxymethyl chitosan/sodium alginate (CMCS/SA) as the matrix, co -loaded with chlorogenic acid (CGA) and astragalus polysaccharide (APS) via electrospinning. Samples were characterized by SEM, etc. In vitro hemostatic, antibacterial, and cytocompatibility properties were evaluated. A full-thickness skin defect model in STZ-induced diabetic mice was used to evaluate healing efficacy. Mechanisms were explored using histology, immunofluorescence, Western blot, and flow cytometry. Results The nanofiber mat exhibited uniform structure, excellent hemostasis, water absorption, and antibacterial activity. In diabetic mice, it significantly accelerated wound closure, promoted granulation tissue formation, and enhanced re-epithelialization. Mechanistically, the material upregulated the NRF2/HO-1 pathway to eliminate ROS, inhibited NF-κB signaling to reduce TNF-α and IL-6, promoted macrophage polarization from M1 to M2, and enhanced angiogenesis and orderly collagen deposition. Conclusions This study successfully constructed a multifunctional nanofiber mat with synergistic effects of antioxidation, anti-inflammation, immune regulation, and tissue regeneration, providing a new strategy for diabetic wound treatment.