Thermoresponsive in situ forming self-healing hydrogel dressings with pH/glucose dual responsive curcumin release for diabetic wound healing

Diabetic wounds often exhibit poor angiogenesis, infection, and prolonged inflammation, posing significant challenges for effective treatment. To address these issues, the thermoresponsive self-healing hydrogel dressings based on hydroxybutyl chitosan and 4-carboxyphenylboronic acid was developed for the delivery of curcumin. The hydrogel exhibited unique properties, including thermoresponsive sol-gel irreversibility, efficient self-healing, and pH/glucose responsive drug release. The irreversible gelation behavior was attributed to the formation of a strong dual crosslinking network involving hydrogen bonds and dynamic boronate ester interactions. Furthermore, the hydrogel dressings exhibited excellent self-healing properties and an injectable nature, making it suitable for in situ wound dressing applications. The pH/glucose dual-responsive release of curcumin was further verified, with accelerated release under acidic conditions and hyperglycemic environments, potentially benefiting diabetic wound treatment. The in vitro studies confirmed the hydrogel's antibacterial, antioxidant and anti-inflammatory activity and ability to promote cell migration and blood coagulation. The in vivo experiments further validate the hemostatic efficacy. This work presents a novel strategy for constructing self-healing, thermoresponsive hydrogel dressings with pH/glucose dual-responsive drug delivery capabilities for the effective management of chronic diabetic wounds.