Multifunctional conductive hydrogel integrating exosome delivery and electrical stimulation for enhanced diabetic...

Diabetic wound healing is severely hampered by persistent inflammation, vascular dysfunction, infection risk, and oxidative stress. To overcome these challenges, we developed a multifunctional conductive hydrogel platform (Gel@Exo-ES). This system integrates exosomes derived from adipose-derived mesenchymal stem cells into a dynamic hydrogel network formed by cross-linking quaternized chitosan-polyaniline (QCS-PANI) with oxidized dextran (ODex). The resulting hydrogel exhibits good injectability, pH-responsive degradability, high antibacterial activity and conductivity. When combined with electrical stimulation, the Gel@Exo-ES significantly enhanced the proliferation, migration, and differentiation of fibroblasts (NIH-3T3), endothelial cells (HUVECs), and macrophages (Raw 264.7) in vitro. This synergy is attributed to the biocompatible hydrogel matrix, electrical stimulation-activated pro-healing signaling, and exosome-mediated bioactive cue delivery. In a diabetic rat model, the Gel@Exo-ES markedly accelerated wound closure by recruiting macrophages, upregulating IL-10 to drive M2 polarization, and thereby alleviating inflammation. The treatment concurrently enhanced re-epithelialization, collagen deposition, and angiogenesis. These findings demonstrate that the combined strategy of exosome-loaded conductive hydrogel and electrical stimulation presents a highly promising therapeutic platform for diabetic wound repair.