Multifunctional ZnO nanoflower-integrated supramolecular dual-network hydrogel to remodel regeneration microenvironment for infected wound healing

Infected wounds present a formidable clinical challenge, in which persistent bacterial colonization, excessive oxidative stress, and dysregulated inflammation converge to impair tissue regeneration. Here, we developed ZNFs@GA/GelMA, a multifunctional supramolecular dual-network hydrogel for infected wound therapy. The ZNFs@GA/GelMA hydrogel dressing system was constructed by integrating glycyrrhizic acid (GA), zinc oxide nanoflowers (ZNFs), and gelatin methacryloyl (GelMA). In this design, GA-driven supramolecular self-assembly first forms an injectable and defect-adaptive physical network, followed by photoinitiated GelMA polymerization to generate a structurally stable dual-network for conformal wound coverage. The incorporated ZNFs endowed the hydrogel with efficient antibacterial activity against methicillin-resistant S. aureus (MRSA) and E. coli . In vitro , ZNFs@GA/GelMA decreased reactive oxygen species (ROS) levels, shifting macrophage polarization toward an anti-inflammatory state. In vivo studies demonstrated that ZNFs@GA/GelMA effectively reduced bacterial burden and inflammatory responses, promoted angiogenesis and extracellular matrix remodeling, and accelerated infected wound closure. Overall, ZNFs@GA/GelMA provides a promising multifunctional dressing strategy for the management of infected wounds.