Infection protection, immune regulation and epithelial regeneration trifunctional hydrogel for treatment of burn wounds

Severe burn wounds are characterized by epithelial disruption and persistent inflammation, which impede re-epithelialization and heighten susceptibility to bacterial colonization and invasion, thereby posing serious clinical risks. To address these challenges, we developed an innovative smart hydrogel (Ag-IMP-U@Cur), in which uridine (U) is incorporated as a backbone-forming component via reversible boronate ester bonds with phenylboronic acid, thereby endowing the hydrogel with dual functions of acidic microenvironment responsiveness and promotion of re-epithelialization. The Ag-IMP complex serves as a structural scaffold that reinforces the network stability, while the combination of Ag-IMP and Cur-loaded ZIF-8 (Cur-ZIF-8) imparts controlled-release, antibacterial, and anti-inflammatory properties. In vitro and in vivo studies demonstrate that this hydrogel markedly suppresses infection and inflammation while accelerating wound closure. Collectively, this work introduces an innovative strategy that integrates a nucleoside unit, metal ions, and a phytochemical into a responsive multifunctional hydrogel, offering a promising therapeutic avenue for severe burn injuries. • Integrates nucleoside-metal-herbal triad into a responsive multifunctional hydrogel. • Uridine, Ag–IMP, and ZIF-8@Cur function synergistically to provide antibacterial, anti-inflammatory, and epithelial-regenerative activities. • ZIF-8 enhances curcumin stability, enabling pH-responsive release triggered by inflammation in burn wound microenvironments. • The hydrogel promotes re-epithelialization and improves immune microenvironment remodeling during wound healing. • The multifunctional hydrogel accelerates burn wound closure and supports tissue reconstruction in vivo. ”