Dual-Supramolecularly Reinforced Quaternary Ammonium Hydrogel for Contact-Active Infected Wound Repair

Abstract Infected wound repair requires hydrogel dressings that maintain antibacterial contact at wet, exudative, and mechanically dynamic tissue interfaces. Quaternary ammonium hydrogels provide intrinsic contact-active antibacterial activity, yet their performance is often limited by insufficient wet adhesion, weak network stability, and poor self-healing. Here, we report a dual-supramolecularly reinforced antibacterial hydrogel, PDQE/PAGD-gel, constructed by integrating a quaternary ammonium bactericidal network with β-cyclodextrin-grafted poly(vinyl alcohol) reinforcement. In this design, quaternary ammonium groups provide membrane-disruptive contact bactericidal activity, while β-cyclodextrin-grafted poly(vinyl alcohol) reinforces the hydrated network through dual supramolecular interactions, including β-cyclodextrin–alkyl host–guest association and hydrogen bonding. Freeze–thaw-induced PVA crystalline domains further serve as physical cross-linking points to improve network stability. This integrated network preserves antibacterial cationic accessibility while improving wet-tissue attachment, mechanical recovery, and interfacial stability. PDQE/PAGD-gel exhibited a high equilibrium swelling ratio of 1052.2%, recovered mechanical integrity after damage, and achieved more than 99.5% contact bactericidal efficiency against Staphylococcus aureus and Escherichia coli within 140 min. It also showed low cytotoxicity, increased the L929 scratch closure rate to 65.4%, and maintained hemocompatibility with hemolysis below 4.0%. In a Staphylococcus aureus-infected full-thickness mouse wound model, PDQE/PAGD-gel reduced bacterial burden and accelerated wound closure to 94.4% by day 12, accompanied by enhanced re-epithelialization and collagen deposition. This work establishes a dual-supramolecular physical-reinforcement strategy for contact-active antibacterial hydrogels in infected wound repair.