Thermosensitive Injectable Sacran-Based Hydrogel with Superbroad Hydrophobic Domains for Rigid Drug-Controlled...

Persistent bacterial infections and prolonged inflammation often complicate full-thickness skin wound healing, underscoring the limitations of current dressings and the overuse of antibiotics. Herein, we developed a novel injectable hydrogel for full-thickness wound repair. The hydrogel matrix is composed of sacran, a supergiant polysaccharide with broad hydrophobic domains and abundant hydroxyl groups. Thermosensitivity was conferred upon the matrix through the incorporation of poly(ethylene glycol)-block-poly(propylene glycol)-block-poly(ethylene glycol). Two rigid bioactive molecules, tannic acid (TA) and dipotassium glycyrrhizinate (DG), were co-loaded within the hydrogel. Their sustained release was achieved by the strong hydrophobic interactions inherent to sacran, which were further stabilized by hydrogen bonding. The synergistic drugs effectively modulate the wound microenvironment by exerting ∼100% antibacterial efficacy against both Gram-positive and Gram-negative bacteria, significant reactive oxygen species (ROS) scavenging (>94%2,2-diphenyl-1-picrylhydrazyl (DPPH) scavenging), suppression of pro-inflammatory cytokines (interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α)), and pro-angiogenic motion of angiogenesis and collagen deposition. In vivo studies confirmed accelerated wound closure, complete re-epithelialization, robust neovascularization, and appendage regeneration, significantly surpassing commercial Tegaderm performance. This multifunctional sacran-based injectable hydrogel emerges as a highly promising biomaterial, establishing a synergistic therapeutic strategy for complex skin injuries and advanced wound care.