Ginsenoside Rg5 nanomedicine composited hydrogel with metabolic regulation and immunomodulation properties for tunneling diabetic wounds therapy

Diabetic wounds behaved delayed healing mainly due to impaired metabolism, dysregulated inflammation, and unique tunneling morphology. Herein, a customized nanocomposite hydrogel for diabetic wounds therapy was designed, demonstrating injectability, shape-adaptivity, and mechanical durability that adapt to the tunneling wound morphology. The hydrogel performed controlled drug release for metabolic regulation and immunomodulatory under topical administration. This hydrogel consists of oxidized anredera cordifolia polysaccharide (OACS), adipic dihydrazide grafted collagen fiber (CF-ADH), and ginsenoside Rg5 loaded polyethyleneimine grafted F127 nanoparticles (F127-PEI@Rg5 NPs). Triple dynamic bonds contributed to the fast cross-linking reconstitution during shape-remodeling, including the acylhydrazone and amine bonds formed from CF-ADH and F127-PEI@Rg5 NPs with OACS, and the electrostatic interactions between the inherent carboxyl groups and protonated amino groups in the materials. The nanolization and two-step loading of Rg5 leaded to improved bioavailability and prolonged drug action time. As a result, this hydrogel exhibited expected regulation for key enzymes in glycolysis, and relieved insulin resistance, thus providing an adequate energy supply for tissue remolding. Additionally, it increased macrophages number and promoted macrophages polarization, thus breaking the prolonged inflammation of diabetic wounds. In vivo experiments showed that the healing period was shortened by 34%, suggesting a promising dressing for diabetic wounds.