Composite Hydrogel Using Methacrylated Silk Fibroin and Mercaptolated Hyaluronic Acid with Encapsulating Zinc-Quercetin Nanozyme

Given the urgent need to regulate oxidative stress microenvironments in chronic wound healing, hydrogel dressings that simultaneously integrate antioxidant, antibacterial, mechanically adaptive, and biocompatible properties are highly desirable. In this study, a natural polymer-based composite hydrogel dressing loaded with zinc-quercetin nanozyme (Zn-Q) was designed. The gel skeleton was constructed via a dual network of photocrosslinked methacrylated silk fibroin (SilMA) and mercaptolated hyaluronic acid (HA-SH) via thiol-ene click chemistry, with the catalase (CAT)-like Zn-Q nanozyme encapsulated in situ within the network, thereby achieving synergy between chemical crosslinking and dynamic metal-polyphenol coordination. Systematic characterization revealed that Zn-Q nanozyme adopted a stable octahedral coordination configuration, and its continuous porous structure exposed abundant catalytically active sites. The composite hydrogels exhibited a highly interconnected, three-dimensional (3D) porous morphology, with swelling ratios that increased significantly with Zn-Q nanozyme content (up to around 1082%). Rheological and mechanical tests demonstrated that although incorporating the nanozyme reduced the storage modulus, the reversible physical crosslinks formed via hydrogen bonding and coordination interactions endowed the material with excellent tensile toughness and energy-dissipation capacity, exhibiting typical Mullins softening behavior. Functional evaluation showed that Zn-Q nanozyme conferred superior free radical scavenging capability to the hydrogels and exerted dose-dependent inhibition against both Staphylococcus aureus and Escherichia coli. Furthermore, the hydrogels exhibited favorable adhesion to various wet organs and heterogeneous material surfaces, with hemolysis rates below 5% and cell viability exceeding 100% after 3 days of culturing with fibroblasts, confirming their excellent hemocompatibility and cytocompatibility. This study provides an experimental basis for developing a new type of wound repair materials that integrate antioxidant, anti-infective, and mechanically adaptive properties, holding significant application potential in oxidative stress-related tissue repair fields.