Drug-Loaded Passive Cooling Hydrogels for Synergistic Thermal and Anti-Inflammatory Regulation of Skin Wounds.

Chronic inflammation and inflammation-associated local microenvironmental imbalance are critical barriers to effective wound healing, while conventional dressings remain functionally limited. Here, we developed a drug-loaded passive cooling nanocomposite hydrogel that can simultaneously regulate the physical temperature and biochemical wound microenvironment. The hydrogel is constructed from a poly(vinyl alcohol)-sorbitol network incorporating sulfated cellulose nanocrystals, silica nanoparticles, and salidroside, a potent anti-inflammatory phytochemical, achieving both exceptional passive cooling with a temperature drop of 6.2°C compared to non-covered control under sunlight and the sustained release of salidroside. In vitro, the hydrogel exhibits time-dependent antibacterial efficacy over 97% bacterial inhibition and effectively suppresses inflammation. In a murine full-thickness wound model, the hydrogel promoted local cooling and accelerated wound closure, achieving near-complete healing by day 11, earlier than the phosphate-buffered saline control. Histological analyses confirm attenuated inflammation and enhanced tissue remodeling, as evidenced by suppressed TNF-α expression and CD68 macrophage infiltration, increased α-SMA myofibroblasts, and organized collagen deposition. This work introduces a cooling-and-curing strategy, where material enables physical cooling and localized drug delivery to operate synergistically to disrupt the inflammatory cycle, offering a transformative platform for intelligent wound management.