Peptide-Zinc Nanoflower Hydrogel for Diabetic Wound Healing
Refractory diabetic wounds are chronic healing disorders characterized by a complex pathological microenvironment involving excessive oxidative stress, persistent inflammation, bacterial infection, and impaired angiogenesis. Existing functional nanobiomaterials often exhibit rapid release and limited therapeutic functionality, resulting in insufficient retention at wound sites and inadequate regulation of the different stages of wound healing. To address these limitations, we developed a composite hydrogel incorporating organic-inorganic peptide-zinc nanoflowers for sustained local delivery. The nanoflowers were formed through the co-assembly of Zn²⁺ with azide-functionalized FP2 (N₃-ERGVVSIKGV) and subsequently covalently immobilized within a click-crosslinked hyaluronic acid network via strain-promoted azide-alkyne cycloaddition. The hierarchical nanoflower architecture, covalent immobilization, and hydrogel network confinement collectively prolonged local retention and enabled sustained release of the bioactive components. The resulting hydrogel regulated the diabetic wound microenvironment through antibacterial, antioxidant, anti-inflammatory, and pro-angiogenic activities, thereby promoting tissue regeneration and accelerating wound closure. These findings demonstrate a multifunctional sustained-delivery strategy for the treatment of complex diabetic wounds.