A Multifunctional Ionic Hydrogel with Antibacterial, Antioxidant, and Pro-regenerative Properties for Diabetic Wound Healing

Abstract Diabetic wounds usually face persistent challenges from bacterial colonization, disorganized microenvironment, and accompanied by a prolonged delay in tissue repair. Herein, we developed a multifunctional ionic hydrogel (GBPLB) constructed by benzyl isothiocyanate (BITC)-grafted gelatin and polyvinyl alcohol-ionic liquid network to achieve efficient repair of infected wound healing. Leveraging the cationic antimicrobial activity of the ionic liquid and the rapid release of BITC via the low-pH-responsive cleavage of Schiff base bonds, this hydrogel demonstrates exceptional antimicrobial efficacy against E. coli, S. aureus, and MRSA. Furthermore, as the BITC grafted onto the biodegradable gelatin is released slowly, it remodels the microenvironment through sustained antimicrobial, antioxidant and anti-inflammatory effects. The in vivo experiments also showed that GBPLB hydrogel dressing not only rapidly stopped the bleeding of arterial in mouse tail amputation models but also significantly accelerated wound healing in a full-thickness skin wound model. Furthermore, RNA-seq results revealed the upregulation of multiple signaling pathways related to wound repairing. This ionic hydrogel is not only useful for diabetic wounds but also potentially applicable to other diseases with microenvironment disorder, offering a significant impact on the field of tissue regeneration.