Multifunctional Thiolated Hyaluronic Acid-graft-PEDOT Dressing With Antifouling, On-Demand Drug Delivery and Electrical Stimulation for Wound Healing.

Recent advances in electro-responsive wound dressings have enabled on-demand drug delivery or electrical stimulation (ES) to accelerate healing; however, integrating both functions within a single platform remains challenging. Here, we report a multifunctional dressing based on a conductive, porous substrate comprising a thiolated hyaluronic acid (THA)-grafted PEDOT copolymer, P(EDOT-co-EDOT-g-THA). The material is fabricated by copolymerizing 3,4-ethylenedioxythiophene (EDOT) and S-((2,3-dihydrothieno[3,4-b][1,4]dioxin-2-yl)methyl)ethanethioate (EDOT-SAc) on flexible Au-coated electrospun PCL fiber mats, followed by electrochemical activation to generate thiols for THA conjugation. The conjugated THA can be released in a controlled manner via reductive cleavage of disulfide bonds (-0.8 V vs. Ag/AgCl). THA incorporation enhances hydrophilicity and conductivity, while forming a hydrated antifouling interface that resists protein adsorption and cell adhesion. In vitro studies using NIH 3T3 fibroblasts show that electrochemically released THA retains bioactivity, promoting cell proliferation, migration, and wound closure comparable to free THA. Furthermore, sequential THA release and ES induce reversible cell detachment without cytotoxicity and enhance intercellular F-actin polymerization. Collectively, this platform functions as a dynamic biointerface integrating antifouling capability, controlled biomolecule delivery, and electrical stimulation, highlighting its potential as a multifunctional wound dressing for advanced therapeutic applications.