Sprayable NIR/pH-responsive NSC/PF127 hydrogel loaded with MoO₂, ciprofloxacin, and FGF-2 for enhanced antibacterial and pro-regenerative infected wound healing

Abstract

Abstract Infected wounds represent a significant clinical burden owing to persistent infection, excessive inflammation, and impaired tissue regeneration. To overcome these limitations, we developed a sprayable N-succinyl chitosan/Pluronic F127 (NSC/PF127) hydrogel incorporating MoO₂ nanoparticles, ciprofloxacin, and fibroblast growth factor-2 (FGF-2). At body temperature, the hydrogel rapidly transitions from a solution to a gel and responds to both pH changes and near-infrared (NIR) irradiation. MoO₂ exhibits NIR-mediated photothermal activity, while CIP and FGF-2 are released in a sustained and pH-dependent manner, thereby maintaining antibacterial efficacy and growth factor bioactivity. In vitro studies demonstrated excellent cytocompatibility and significantly enhanced fibroblast and keratinocyte migration. The combined photothermal effect and antibiotic therapy effectively suppressed bacterial growth and disrupted established biofilms. In a rat model of Staphylococcus aureus-infected full-thickness wounds, the hydrogel composite significantly accelerated healing, reduced inflammation, promoted collagen deposition and angiogenesis, and enhanced tissue regeneration. Biochemical and gene expression analyses further indicated reduced oxidative stress and improved tissue regeneration. This multifunctional, sprayable hydrogel combines targeted antibacterial action with sustained pro-regenerative signaling, offering a promising strategy for further preclinical investigations of infected wound management.