A Sericin-Reinforced Poly(vinyl alcohol) Composite Hydrogel Integrating Sericin-Associated Silver Nanoparticles and Dual Growth Factors for Diabetic Wound Repair

Abstract Diabetic wound repair requires polymeric dressings that combine structural stability, swelling behavior, antibacterial activity, and biological support within a single material platform. Here, we report a sericin-reinforced poly(vinyl alcohol) (PVA) composite hydrogel incorporating silver nanoparticles formed in a sericin-containing matrix (Sericin-AgNPs) and the complementary growth factors hepatocyte growth factor (HGF) and keratinocyte growth factor-2 (KGF-2). The hydrogel was prepared through a freeze–thaw cross-linking strategy that generated a porous, elastic, and conformable polymer network while using sericin as a biocompatible matrix component that participates in the in situ formation of AgNPs. The selected SAP5 formulation exhibited a porosity of 62.02%, an equilibrium swelling ratio of 59.13%, and more than 70% mass retention after 28 days. In vitro assays showed that the Sericin-AgNPs provided broad-spectrum antibacterial activity, achieving nearly complete inhibition of E. coli and >90% inhibition of S. aureus at 50 mg/L, while maintaining high HaCaT cell viability at the selected working concentration. The resulting Sericin-AgNPs/PVA hydrogel incorporating HGF and KGF-2 (SAP-HK) supported keratinocyte proliferation and migration in vitro and did not induce a detectable pro-inflammatory response in RAW264.7 macrophages. In a full-thickness diabetic murine wound model, SAP-HK treatment achieved a wound healing rate of approximately 94% by day 14, compared with approximately 55–57% in the PBS and SAP groups, and was accompanied by qualitative histological features of epidermal regeneration, granulation tissue formation, and collagen deposition. Overall, SAP-HK provided antibacterial protection and growth-factor-associated regenerative support within a physically cross-linked composite dressing platform for diabetic wound repair.