In-situ doping of a conductive hydrogel with low protein absorption and bacterial adhesion for electrical stimulation of chronic wounds.

Electrical stimulation (ES) via electrodes is promising for treating chronic wounds, but this electrode-based strategy is unable to stimulate the whole wound area and the therapeutic outcome may be compromised. In this study, a conductive poly(2-hydroxyethyl methacrylate) (polyHEMA)/polypyrrole (PPY) hydrogel was developed, and 3-sulfopropyl methacrylate was covalently incorporated in the hydrogel's network to in-situ dope the PPY and maintain the hydrogel's conductivity in the weak alkaline physiological environment. The obtained hydrogel was superior to the commercial Hydrosorb® dressing for preventing bacterial adhesion and protein absorption, and this is helpful to reduce the possibilities of infection and secondary damage during dressing replacement. The in vitro scratch assay demonstrates that ES through the hydrogel enhanced fibroblast migration, and this enhancement effect remained even after the ES was ended. The in vivo assay using diabetic rats shows that when ES was conducted with this polyHEMA/PPY hydrogel, the healing rate was faster than that achieved by the electrode-based ES strategy. Therefore, this polyHEMA/PPY hydrogel shows a great potential for developing the next generation of ES treatment for chronic wounds. STATEMENT OF SIGNIFICANCE: Electrical stimulation (ES) via separated electrodes is promising for treating chronic wounds, but this electrode-based strategy is unable to stimulate the whole wound area, compromising the therapeutic outcome. Herein, a hydrogel was developed with stable electrical conductivity in the physiological environment and strong resistance to protein absorption and bacterial adhesion. The in vitro and in vivo tests proved that ES applied through the flexible and conductive hydrogel that covered the wound was superior to ES through electrodes for promoting the healing of the chronic wound. This hydrogel-based ES strategy combines the advantages of ES and hydrogel dressing and will pave the way for the next generation of ES treatment for chronic wounds.