Dual Dynamic Coordination-Driven Hydrogels Accelerate Infected Wound Healing by Enhancing Nerve Regeneration

Wound healing, a complex process involving hemostasis, inflammation, proliferation, and remodeling, is often hindered by factors like infection or a weakened immune response. Existing studies often neglect the crucial role of nerve regeneration. Our study introduces a novel hydrogel system using functionalized bisphosphonic acid grafted onto sodium alginate, combined with hyaluronic acid and metal ions (Fe 3+ and Zn 2+ ), to enhance wound healing in infectious environments. The interaction between bisphosphonates and Zn 2+ forms a secondary network that facilitates the release of Fe 3+ and Zn 2+ ions. This mechanism offers broad-spectrum antibacterial action and regulates the immune environment, promoting M2 macrophage polarization. Additionally, the hydrogel supports neurogenesis and angiogenesis, essential for complete tissue repair. Enhancing nerve regeneration restores neural function and accelerates wound healing. Its injectability, self-healing properties, and biocompatibility make this hydrogel a promising candidate for advanced wound dressings, potentially reducing healing time and improving infected wound management.