Tunicate cellulose nanocrystals strengthened injectable stretchable hydrogel as multi-responsive enhanced antibacterial wound dressing for promoting diabetic wound healing

Abstract

The intricate microenvironment of diabetic wounds characterized by hyperglycemia, intense oxidative stress, persistent bacterial infection and complex pH fluctuations hinders the healing process. Herein, an injectable multifunctional hydrogel (QPT_x) was developed, which exhibited excellent mechanical performance and triple responsiveness to pH, temperature, and glucose due to dynamic covalent cross-linking involving dynamic Schiff base bonds and phenylboronate esters with phenylboronic-modified quaternized chitosan (QCS-PBA), polydopamine coated tunicate cellulose crystals (PDA_n@TCNCs) and polyvinyl alcohol (PVA). Furthermore, the hydrogels can incorporate insulin (INS) drugs to adapt to the complex and variable wound environment in diabetic patients for on-demand drug release that promote diabetic wound healing. Based on various excellent properties of the colloidal materials, the hydrogels were evaluated for self-healing, rheological and mechanical properties, in vitro insulin response to pH/temperature/glucose release, antibacterial, antioxidant, tissue adhesion, coagulation, hemostasis in vivo and in vitro, and biocompatibility and biodegradability. By introducing PDA_n@TCNCs particles, the hydrogel has photothermal antibacterial activity, enhanced adhesion and oxidation resistance. We further demonstrated that these hydrogel dressings significantly improved the healing process compared to commercial dressings (Tegaderm™) in full-layer skin defect models. All indicated that the glucose-responsive QPT_x hydrogel platform has great potential for treating diabetic wounds.