Peptide-coordinated silver nanoassemblies: a multifunctional hydrogel platform for infected diabetic wound healing

Diabetic chronic wounds remain a major clinical challenge due to persistent infection, excessive inflammation, and impaired tissue regeneration. Herein, we report a multifunctional peptide-based antibacterial hydrogel (PAHG) for treating infected wounds, constructed through the incorporation of Cys-Arg-NH₂ (CR)-Ag nanoassemblies into a bioactive matrix. In this design, the CR dipeptide enables in situ reduction and stable coordination of silver ions, yielding CR-Ag nanoassemblies with controlled silver release and enhanced biocompatibility. Co-assembly of this antibacterial component with chitosan, gelatin, collagen, and epidermal growth factor (EGF) affords a three-dimensional hydrogel network that provides a moist wound microenvironment, structural support, and sustained release of pro-regenerative cues. The resulting PAHG system exhibits excellent antibacterial activity against Escherichia coli and methicillin-resistant Staphylococcus aureus, with inhibition efficiencies exceeding 80%, while maintaining high cytocompatibility with human skin fibroblasts (∼150% viability). In a diabetic infected wound model, PAHG significantly accelerates wound healing, achieving nearly complete closure within 12 days, accompanied by enhanced collagen deposition and no noticeable histopathological abnormalities in major organs. By integrating molecularly engineered antibacterial nanoassemblies with rationally designed multicomponent hydrogels, this work provides a promising strategy for the development of bio-based antimicrobial materials and chronic wound dressings.