Pulsed Electrical Stimulation Benefits Wound Healing by Activating Skin Fibroblasts Through the TGFβ1/ERK/NF-κB Axis

Background: Dermal fibroblasts activated by conductive polymer-mediated electrical stimulation (ES) have shown myofibroblast characteristics that favor wound healing. However, the signaling pathway related to this phenotype switch remains unclear, and the in vivo survival of the electrically activated cells has never been studied.

Methods: Primary human skin fibroblasts were exposed to pulsed-ES mediated through polypyrrole (PPy) coated fabrics. The expression of α-smooth muscle actin (α-SMA) and the signaling pathways were investigated by ELISA, Western blot and specific inhibition test, and immunocytochemistry staining as well as qRT-PCR analysis. In vivo implantation was performed in a mouse model to clarify the cell fate or contractile phenotype maintenance following ES stimulation.

Results: We demonstrated the upregulation of TGFβ1 and phosph-ERK, and the NF-κB nuclear enrichment in the ES-activated cells. The ES-activated fibroblasts retained high level of α-smooth muscle actin expression even after prolonged subculture. Subcutaneous implantation for 15 days revealed more human myofibroblasts in the experimental groups.

Conclusions: These findings demonstrate for the first time the involvement of the TGFβ1/ERK/NF-κB signaling pathway in ES-activated fibroblasts. The ES induced phenotype switch proves stable in subculture and in animal, pointing potential application in wound healing.

General Significance: Reveal of how ES activates cells and the implication of ES activated cells in wound healing.