Electrical stimulation (ES) has long been used as an alternative clinical treatment and an effective approach to modulate cellular behaviours. In this work we investigated the effects of ES on human skin fibroblast activity, myofibroblast transdifferentiation and the consequence on wound healing. Normal human fibroblasts were seeded on heparin-bioactivated PPy/PLLA conductive membranes, cultured for 24 h, and then exposed to ES of 50 or 200 mV/mm for 2, 4, or 6 h. Following ES, the cells were either subjected to various analyses or re-seeded to investigate their healing capacity. Our findings show that ES had no cytotoxic effect on the fibroblasts, as demonstrated by the similar LDH activity levels in the ES-exposed and non-exposed cultures, and by the comparable cell viability under both conditions. Furthermore, the number of viable fibroblasts was higher following exposure to 6 h of ES than in the non-exposed culture. This enhanced cell growth was likely due to the ES up-regulated secretion of FGF-1 and FGF-2. In an in vitro scratch-wound assay where cell monolayer was used as a healing model, the electrically stimulated dermal fibroblasts migrated faster following exposure to ES and recorded a high contractile behaviour toward the collagen gel matrix. This enhanced contraction was supported by the high level of α-smooth muscle actin expressed by the fibroblasts following exposure to ES, indicating the characteristics of myofibroblasts. Remarkably, the modulation of fibroblast growth continued long after ES. In conclusion, this work demonstrates for the first time that exposure to ES promoted skin fibroblast growth and migration, increased growth factor secretion, and promoted fibroblast to myofibroblast transdifferentiation, thus promoting wound healing.

Research on the cellular response to electrical stimulation (ES) and its mechanisms focusing on potential clinic applications has been quietly intensified recently. However, the unconventional nature of this methodology has fertilized a great variety of techniques that make the interpretation and comparison of experimental outcomes complicated. This work reviews more than a hundred publications identified mostly from Medline, categorizes the techniques, and comments on their merits and weaknesses. Electrode-based ES, conductive substrate-mediated ES, and noninvasive stimulation are the three principal categories used in biomedical research and clinic. ES has been found to enhance cell proliferation, growth, migration, and stem cell differentiation, showing an important potential in manipulating cellular activities in both normal and pathological conditions. However, inappropriate parameters or setup can have negative effects. The complexity of the delivered electric signals depends on how they are generated and in what form. It is also difficult to equate one set of parameters with another. Mechanistic studies are rare and badly needed. Even so, ES in combination with advanced materials and nanotechnology is developing a strong footing in biomedical research and regenerative medicine.