Superstretchable and Tough Physical Cross-Linking Hydrogels with Dual pH and Temperature Responsiveness for In Vivo Treatment of Staphylococcus aureus-Infected Wounds

Developing a single hydrogel with comprehensive wound healing functions is challenging. We developed a composite hydrogel wound dressing with thermal and pH responsiveness, demonstrating antibacterial and biocompatible properties in rats with Staphylococcus aureus-infected wounds. Sodium alginate cross-linked by Ca²⁺ served as the continuous phase, while thermosensitive poly(isopropylacrylamide), laponite, lecithin, gelatin, and antibacterial ZIF-8 supported by tannic acid-induced Ag nanoparticles formed the dispersed phase. This hydrogel exhibits impressive mechanical properties, including >3100% breaking elongation and 0.5 MJ/m³ toughness, able to withstand 56 times its own weight, highlighting its ductility and ability to prevent structural damage in animal models. It also demonstrates excellent thermoresponsive self-contraction and tissue adhesion, promoting wound closure. Biochemically, it supports wound healing with temperature-dependent drug release, anti-infection, and antioxidation properties. In vivo studies on S. aureus-infected skin defects show accelerated wound closure, increased granulation tissue thickness, collagen deposition, and vascularization, demonstrating its potential as an effective wound dressing.