Self-Adaptive Allantoin@ZIF8 Nanocomposite Hydrogel with Resveratrol Synergy for MRSA-Infected Wound Regeneration

Infected wounds present a formidable challenge to healing due to their complex pathological microenvironment, whereas conventional dressings are often functionally limited and ill-suited to adapt to dynamic wound changes. In this study, based on allantoin-loaded ZIF8 nanoparticles (Alla@ZIF8) and methacrylated quaternary ammonium carboxymethyl chitosan/resveratrol composite hydrogels (RMQCC), we designed and developed an adaptive multifunctional hydrogel system (Alla@ZIF8-Gel). This nanocomposite hydrogel exhibited multiple intelligent features, including pH-responsiveness and morphological adaptability. The quaternary ammonium carboxymethyl chitosan imparted well biocompatibility and robust antimicrobial properties. Electrostatic interactions and hydrogen bonds endowed hydrogels with excellent injectability and self-healing capabilities. The ZIF8 nanoparticles enabled the intelligent, on-demand release of allantoin, thereby promoting tissue regeneration. Resveratrol conferred potent antioxidant, anti-inflammatory, and immunomodulatory effects. The Alla@ZIF8-Gel dynamically modulated drug release kinetics in response to the wound microenvironment, synergistically delivering antibacterial, antioxidant, anti-inflammatory, and tissue-regenerative functions. Both in vitro and in vivo experimental results demonstrated that this adaptive hydrogel markedly accelerated the healing of MRSA-infected wounds, suppressed bacterial proliferation, alleviated oxidative damage and inflammatory responses, and enhanced collagen deposition, re-epithelialization, and neovascularization. This work provides a novel design paradigm for the development of intelligent, multifunctional therapeutic materials for infected wound management, with significant translational potential for clinical application.