A pH/heating-driven curdlan-based complementary hydrogel for promoting full-thickness skin wound healing

Curdlan (CUR)-based hydrogels have shown promise for wound healing but suffer from poor flexibility, high brittleness, and limited drug-loading capacity. To overcome these limitations, a curdlan-based complementary hydrogel (CM Gel) was developed by integrating CUR with mangiferin (MF), a polyphenol capable of self-assembly. Non-covalent interactions between CUR and MF led to a stable and flexible network with improved mechanical properties and gelation under mildly acidic pH conditions (pH ∼6.5), which aligns with skin wound conditions. Furthermore, the hydrogel was loaded with dihydromyricetin (DMY), a natural antibacterial agent, using a solvent-free one-pot pH/heating-driven process to fabricate the enhanced comprehensive hydrogel properties D@CM Gel. Multispectral analysis suggested that MF, CUR, and DMY were transformed from the crystalline state to the amorphous state. In vitro studies confirmed its potent antibacterial activity against S. aureus and E. coli, strong antioxidant capacity, and effective biofilm inhibition capacity. In an S. aureus-infected full-thickness wound model, D@CM Gel significantly accelerated wound closure, reduced inflammation (TNF-α, IL-6), promoted collagen deposition and angiogenesis (VEGF, CD31, α-SMA), and outperformed commercial hydrogel dressings with excellent biocompatibility. These findings suggest that D@CM Gel is a promising and easily fabricated wound dressing with synergistic therapeutic functions for treating infected skin wounds.