An Injectable, Conductive PEDOT:PSS-Doped Hydrogel Combined with Electrical Stimulation for Full-Thickness Wound-Healing Enhancement

The persistent nonhealing of wounds constitutes a formidable clinical predicament. While electrical stimulation (ES) has exhibited substantial potential in expediting wound reparative processes, the development of conductive wound dressings integrating shape adaptability, biocompatibility, and stable electrical performance in a synergistic manner remains rather constrained. In this study, an injectable conductive hydrogel (GMCS@PP), based on gelatin methacryloyl (GelMA) and carboxymethyl chitosan (CMCS), with the introduction of poly(3,4-ethylenedioxythiophene): polystyrenesulfonate (PEDOT:PSS), was successfully developed. The hydrogel exhibited excellent injectability, good stretchability (∼84%), compressibility (∼50%), alongside an electrical conductivity analogous to that of native skin (∼1.14 × 10 –3 S m –1 ). The effective facilitation of fibroblast proliferation and migration by the conductive hydrogel under exogenous electrical stimulation (EES) was demonstrated via in vitro experimental investigations. The in vivo experiment was conducted using a full-thickness skin defect model. The combinatorial therapy of the hydrogel and EES significantly accelerated wound closure. Histological analyses revealed a coordinated healing process, characterized by a shortened inflammatory phase via the downregulation of TNF-α, enhanced cellular proliferation associated with increased PCNA expression, and promoted granulation tissue maturation. Furthermore, denser collagen deposition and a more developed functional vascular network, as indicated by CD31 and α-SMA expression, were observed. Overall, this study demonstrates that the PEDOT:PSS-based composite hydrogel functions as an effective electrically active wound dressing and elucidates its multifaceted mechanisms in accelerating tissue regeneration through the coordinated regulation of inflammation resolution, cell proliferation, and angiogenesis. This work proposed a promising strategy and bioelectro platform for the exploration of electronic-based wound management systems.