Multifunctional self-healing hydrogels for chronic wound repair: Design, mechanisms, and applications

Chronic wounds arise from a multifactorial interplay involving persistent hyperglycemia, recurrent infection, tissue ischemia, and sustained inflammation, which collectively disrupt cellular metabolic homeostasis, impair angiogenesis and extracellular matrix remodeling, ultimately leading to impaired healing progression. Multifunctional self-healing hydrogels have become promising biomaterials to solve these problems due to their excellent biocompatibility, self-healing ability and multiple functional properties. These hydrogels can autonomously restore their structure and function after injury, thus maintaining the therapeutic effect of the wound site. In addition, they exhibit multifunctional properties, including antimicrobial activity, adhesion, hemostasis, anti-inflammatory and antioxidant effects, drug delivery, promotion of angiogenesis and nerve repair, electrical conductivity, and monitoring capabilities, resulting in significantly improved wound healing outcomes. In this paper, the healing process and current status of chronic wounds are first discussed, and then the latest progress in the preparation mechanism, functional properties and mechanical properties of multifunctional self-healing hydrogels is studied. The application of these hydrogels in chronic wound healing is critically analyzed, with a focus on their self-healing mechanisms and functional properties，and it is worth emphasizing the first comprehensive analysis of the hydrogels' function in neurovascular regeneration. In addition, the design related to clinical translation is also discussed. Future research directions are proposed, including the development of smart hydrogels and the exploration of new biomaterials to provide more innovative and effective solutions for chronic wound management. Overall, multifunctional self-healing hydrogels represent a transformative approach to chronic wound healing with great potential for clinical applications.