Body temperature-induced adhesive hyaluronate/gelatin-based hybrid hydrogel dressing for promoting skin regeneration

Skin wound management faces significant clinical challenges, including continuous bacterial infection and inflammation. Therefore, developing removable hydrogel dressings with intrinsic multifunctional properties is highly desirable. In this study, a body temperature-induced adhesive and removable hydrogel was designed to treat skin defect wounds. The HA/Gel-R-Ag hybrid gel was prepared by incorporating a silver ion-crosslinked sulfhydryl hyaluronate/gelatin-based polymeric gel network into a supramolecular rhein gel network, thereby significantly enhancing its mechanical properties. Temperature-responsive gelatin chains give the hybrid gel reversible tissue adhesiveness and detachment, thus avoiding secondary injury to wounds when changing the hydrogels. The hybrid gel exhibited excellent bactericidal ability owing to the antibacterial capacity of the silver ions and rhein. Moreover, both HA and rhein endowed the hybrid gel with immunoregulatory effects by promoting macrophage polarization from pro-inflammatory M1 phenotype to anti-inflammatory M2 phenotype. In a full-thickness skin defect mouse mode, this porous, degradable, and biocompatible HA/Gel-R-Ag hybrid gel boosted skin regeneration by inhibiting inflammation and promoting collagen deposition and angiogenesis. It is thus a simple method for widening the application range of mechanically weak rhein gels and providing a promising wound dressing material with multiple intrinsic functions for treating skin wounds.