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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. [ABSTRACT FROM AUTHOR]

One of the major benefits of a conductive PPy-based substrate is that the mediated electrical stimulation (ES) can be a stimulating factor to promote tissue regeneration. We cultured osteoblast-like Saos-2 cells on a conductive substrate made of biodegradable polylactide (95 wt%) and electrically conducting polypyrrole bioactivated with heparin (PPy/HE) (5 wt%). Using multi-well electrical cell culture plates, the effect of multiple ESs on osteoblast mineralization was investigated at various culture times. As ascertained by ARS, CPC and XPS analyses, the ES was able to promote osteoblast adhesion and growth, resulting in significantly higher calcium and phosphate content in the mineral deposition of the electrically stimulated membranes. Morphology, Ca/P ratio and crystalline structure demonstrated that the minerals on the conductive substrate surface were similar to those found on typical hydroxyapatite. ES also significantly upregulated the expression of the osteoblast-specific markers ALP, BMP2, Runx2 and OC. ES through a synthetic conductive polymer substrate therefore represents a vital option to promote bone regeneration. [ABSTRACT FROM AUTHOR]

Electrically conductive biodegradable composites are useful in biomedical engineering to mediate electrical interactions between cells and electrical components. Because conductive polymers are often subjected to progressive oxidative deterioration and dedoping, their electrical stability in aqueous environment is, therefore, critical. We used cyclic voltammetry (CV) to investigate the electroactivity and stability of conductive membranes made of only 5% conductive polypyrrole (PPy) particles blended with 95% insulating polylactide (PLLA). During 1000 CV scans, the electroactivity of the composite membranes revealed a period of initial activation, followed by a relatively stable period and subsequent slow deterioration process. PPy membranes doped with heparin, a cell-adhesive polysaccharide and polyanion, displayed electrical stability superior to that of PPy membranes doped with chlorine anions. The latter, however, recorded a higher initial electroactivity during the first ca. 150 scans. XPS analysis showed that the deterioration of the electroactivity was likely due to the oxidation of the PPy. ATR-FT-IR and SEM were also used to characterize the materials. The PLLA/PPy membranes were thus electroactive and maximum electroactivity was achieved through an activation process. The heparin-doped PPy composite was electrically stable and may, thus, be used for multiple long-term electrical stimulations. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

A correction to the article "Accelerated osteoblast mineralization on a conductive substrate by multiple electrical stimulation," that was published online on May 13, 2011 is presented.