Ultra-stretchable hydrogel with selenium-doped polypyrrole nanowires enhances wound healing via microenvironment reconstruction and immunomodulation.

Hydrogel dressings have emerged as versatile platforms for wound management. However, the clinical performance of the hydrogel remains limited by insufficient mechanical robustness at joints, where repetitive deformation can compromise structural integrity and delay healing. To address these challenges, a nanocomposite dressing (GD@Bet-NWs) was fabricated by integrating gelatin methacrylate anhydride-grafted with dopamine hydrochloride (GelMA-DA), oxidized Tremella fuciformis polysaccharide (OTFP), carboxymethyl chitosan (CMC), polyvinyl alcohol (PVA), and borax. The hydrogel matrix was further augmented by incorporating selenium-functionalized polydopamine-polypyrrole (Se@PDA-PPy) nanowires (NWs) and Betulin (Bet)- encapsulated Pluronic F127 micelles (BetF127). The incorporation of Se@PDA-PPy NWs endowed the hydrogel with robust mechanical strength, adhesion, and exceptional antibacterial (> 98%) and ROS/RNS-scavenging (> 98%) potential. Encapsulation of Bet into Pluronic F127 micelles significantly improved its aqueous solubility and stability while alleviating pharmacokinetic limitations. In a full-thickness wound model, GD@Bet-NWs promoted re-epithelialization and collagen deposition, achieving 99% wound closure within 14 days. Immunohistochemical and immunofluorescence analyses revealed reduced levels of inflammatory cytokines and increased M2 macrophage polarization. Gene expression profiling further demonstrated the upregulation of immunomodulatory and tissue-regenerative genes, along with the downregulation of pro-inflammatory pathways. Consequently, the GD@Bet-NWs hydrogel dressing holds significant potential as an advanced wound-healing platform.