Hydroxyproline-Modified Chitosan-Based Hydrogel Dressing Incorporated with Epigallocatechin-3-Gallate Promotes Wound Healing Through Immunomodulation

Immunoregulation is an emerging treatment strategy to promote wound healing by modulating the local immune system at the wound site. In this study, an extracellular matrix biomimetic and polysaccharide-based hydrogel was engineered to regulate the wound immune environment through Michael-type addition between maleimidyl pullulan and chitosan modified with hydroxyproline. The proposed hydrogel exhibited favorable injectable and self-healing properties, which facilitated the full coverage of irregularly shaped wounds. A natural polyphenol, epigallocatechin-3-gallate (EGCG), was incorporated into hydrogels, which thereby exhibited excellent biocompatibility, good reactive oxygen species (ROS) scavenging ability, anti-inflammatory activity, and antibacterial properties against S. aureus and E. coli. Furthermore, evaluations of a full-thickness skin defect mice model showed that the hydrogel with EGCG effectively alleviated the inflammatory response by reducing pro-inflammatory cellular infiltration and down-regulating the inflammatory cytokine TNF-α, while up-regulating anti-inflammatory cytokine IL-10. Notably, a faster wound healing rate was also achieved by the better promotion effect of the hydrogel on increasing the formation of re-epithelialization, granulation tissue generation, collagen deposition, and angiogenesis. Therefore, our immunoregulatory strategy showed great potential in the design of biomaterials for wound management.