Polyphenol-Loaded ZnO–CuO Hydrogel with Enhanced Structural and Biological Properties for Advanced Wound Dressing Application

Abstract Chronic wounds are often characterized by persistent inflammation and oxidative stress, which impair fibroblast function, disrupt extracellular matrix formation, and delay tissue regeneration. Bioactive hydrogels that incorporate natural polyphenols and functional nanomaterials offer a promising strategy to accelerate healing through synergistic antioxidant and anti-inflammatory effects, creating a favorable microenvironment for tissue repair. Building on previous work with a ZnO–CuO nanocomposite–embedded PEG–chitosan hydrogel, this study developed a novel polyphenol-loaded ZnO–CuO polysaccharide hydrogel (CPZCH-X) for advanced wound dressing applications. Structural and chemo-mechanical characterization using FTIR, XRD, SEM, UV–Vis spectroscopy, and tensile testing confirmed successful polyphenol incorporation, resulting in improved structural integrity and mechanical stability. The functional assays showed favorable cytocompatibility, hemocompatibility, and wound closure activity, along with regulated inflammatory, oxidative, and repair biomarkers, demonstrating enhanced wound-healing potential. Overall, CPZCH-X is a multifunctional, polyphenol-enriched hydrogel with superior physicochemical and mechanical properties, showing strong potential as a bioactive wound dressing. Future in vivo studies are warranted to validate its therapeutic efficacy and clinical applicability in chronic wound management. Graphical Abstract