Tailoring Injectable Chitosan-Cellulose Quaternary Hydrogels Through Room-Temperature Diels-Alder for Accelerating Wound Healing.

Abstract

The development of injectable hydrogel wound dressings with inherent antibacterial and antioxidant properties for treating full-thickness skin injuries represents one of the most promising solutions in clinical care. In this study, a series of injectable hydrogels with tunable gelation times is designed and prepared through the Diels-Alder (DA) reaction between diene-functionalized quaternary cellulose and maleimide-grafted quaternary chitosan. The high degree of substitution of diene and maleimide groups on these polysaccharides enables the formation of highly crosslinked hydrogels. By fine-tuning the structure of the dienes, the gelation time can be reduced to 4 min at 37 ^°C. Both precursors and hydrogels showed strong antibacterial activity with killing efficacies >98% against E. coli and S. aureus. Meanwhile, the encapsulation of epigallocatechin gallate (EGCG, a green tea derivative) endowed the hydrogel with strong antioxidant performance. Moreover, the hydrogel exhibited good biocompatibility with 100% cell viability for NIH3T3 cells. In vivo wound healing assessment in a mouse full-thickness skin defect model revealed that the optimum hydrogel exhibited significant collagen deposition and vascularization, as well as remarkable regenerative wound healing performance, demonstrating its great potential as a bio-based wound dressing for improving wound healing.