A glucose-triggered self-reinforcing hydrogel based on carboxymethyl chitosan/oxidized hyaluronic acid/borax for delivering nano-selenium and dynamic diabetic wound management

Despite the advances in multifunctional hydrogels for diabetic wound healing, their mismatch with the dynamic healing process and inability to eliminate excess glucose still limit therapeutic efficacy. Herein, we propose a small molecule competition strategy for developing a glucose-triggered self-reinforcing hydrogel dressing with glucose scavenging functions. The hydrogels are based on carboxymethyl chitosan/oxidized hyaluronic acid polymer network, which realizes rapid in situ gelation through Schiff base reaction. The dynamic competition of Schiff base bonds with borax gives the hydrogel excellent self-healing properties and the ability to adapt to the shape of wound. Significantly, the hydrogels also can absorb excess glucose from the wound environment, thus reducing the apoptosis. Meanwhile, the absorbed glucose triggers the self-reinforced behavior of the hydrogel by weakening the competition of borax for the Schiff base bond, which contributes to its continuous adhesion to the wound site. Additionally, the hydrogel showed excellent antibacterial, antioxidant capacity by loading selenium nanoparticles. The animal experiments have revealed that it reprogrammed macrophages through JAK/ STAT pathway to reverse the inflammatory storm and promote angiogenesis and wound healing in diabetic wounds. In conclusion, this study provides new insights into the development of self-reinforcing hydrogels based on polysaccharide in diabetic wound healing.