Genipin-crosslinked chitosan/PVA/silk fibroin hydrogel nanocomposites incorporating silver-quercetin for controlled release and skin wound regeneration

The development of multifunctional hydrogel nanocomposites has attracted significant interest for advanced wound-healing applications. In this study, silver/quercetin (SQ) nanocomposites at different concentrations (0.4, 0.6, 0.8, and 1.0%) were successfully incorporated into genipin-crosslinked chitosan/poly (vinyl alcohol)/silk fibroin hydrogels (SQH). The structural and physicochemical properties of SQ and SQH were systematically characterized using X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FT-IR), UV–visible spectroscopy, and field-emission scanning electron microscopy (FE-SEM). The SQH films exhibited favourable swelling behaviour, enhanced mechanical strength, improved thermal stability, and effective moisture regulation. The tensile strength increased markedly from 0.86 MPa for the neat hydrogel to 12.34 MPa for SQH films, while the water vapour transmission rate (WVTR) decreased from 2249.67 to 631.50 g m −2 day −1 with increasing SQ content, indicating improved barrier properties suitable for wound dressings. Antibacterial activity was assessed against Staphylococcus epidermidis and Proteus mirabilis using the agar well diffusion method. A progressive increase in inhibition zone diameter with increasing SQ concentration was observed, suggesting enhanced antibacterial efficacy of the SQ-loaded hydrogel. Drug release studies confirmed sustained and controlled quercetin release, with the 0.4% SQH formulation best fitting the Korsmeyer-Peppas model (R 2 = 0.9672). MTT assays using NIH-3 T3 fibroblast cells showed excellent cytocompatibility, while in vitro wound-scratch assays demonstrated enhanced cell migration with approximately 95% wound closure after 72 h. Molecular docking studies with the wound-healing-related protein 3SHI revealed strong binding affinity (− 8.50 kcal/mol), supporting the bioactive role of quercetin. Overall, SQ-loaded genipin-crosslinked hydrogels represent a promising multifunctional platform for wound-healing applications.