Shellac nanoparticle based intelligent drug-delivery composite sponge for hemostasis and healing of diabetic wounds

Diabetic chronic wounds pose significant challenges to clinical treatment due to persistent inflammation, impaired angiogenesis, and high infection risk. In this study, we developed an intelligent composite sponge (NSCG) by incorporating naringenin (NGN) loaded shellac nanoparticles (N-SNPs) into a chitosan-gelatin (CG) hydrogel via freeze drying. Physicochemical characterization confirmed that NSCG possesses a porous structure with favorable hydrophilicity, mechanical flexibility, and pH-responsive drug release behavior, and can rapidly release NGN under simulating the pathological microenvironment of infected and inflamed chronic diabetic wounds (pH 8.5). In vitro assays demonstrated that NSCG exhibits strong antioxidant activity, broad spectrum antibacterial efficacy against Staphylococcus aureus (19 mm inhibition zone) and Escherichia coli (21 mm), and excellent hemostatic performance (low blood coagulation index, high red blood cell adhesion, and efficient blood absorption). In vivo evaluations validated its rapid hemostatic capacity in liver and femoral artery hemorrhage models (hemostasis time < 40 s) and excellent biocompatibility with complete degradation within 14 days. In the diabetic mouse wound model, NSCG significantly accelerated wound closure by promoting granulation tissue formation, collagen deposition, and angiogenesis (enhanced CD31 and VEGF expression), while suppressing inflammatory factors (TNF-α and IL-6). These results indicate that NSCG integrates rapid hemostasis, pH-responsive drug release, antioxidant, antibacterial, and biocompatible properties, making it a promising multifunctional dressing for diabetic wound repair and providing a novel strategy for chronic wound management.