Biomedical applications of electrical stimulation

Abstract

This review provides a comprehensive overview on the biomedical applications of electrical stimulation (EStim). EStim has a wide range of direct effects on both biomolecules and cells. These effects have been exploited to facilitate proliferation and functional development of engineered tissue constructs for regenerative medicine applications. They have also been tested or used in clinics for pain mitigation, muscle rehabilitation, the treatment of motor/consciousness disorders, wound healing, and drug delivery. However, the research on fundamental mechanism of cellular response to EStim has fell behind its applications, which has hindered the full exploitation of the clinical potential of EStim. Moreover, despite the positive outcome from the in vitro and animal studies testing the efficacy of EStim, existing clinical trials failed to establish strong, conclusive supports for the therapeutic efficacy of EStim for most of the clinical applications mentioned above. Two potential directions of future research to improve the clinical utility of EStim are presented, including the optimization and standardization of the stimulation protocol and the development of more tissue-matching devices.

Osmolarity-independent electrical cues guide rapid response to injury in zebrafish epidermis

“…Electric currents have been measured emanating from wounds in human skin, and human skin and nasal epithelium both maintain a TEP, suggesting that electric fields may be relevant for wound healing in humans (Foulds and Barker, 1983;Knowles et al, 1981;Reid et al, 2007). Electric stimulation has been explored numerous times in clinical treatments for wounds and ulcers, but the lack of a detailed understanding of the mechanism by which electric fields influence cell behavior has limited progress (Gentzkow et al, 1991;Zhao et al, 2020). Our direct observation of actin polarization in response to electric fields in vivo at rapid timescales of 5-10 minutes bridges the gap between detailed mechanistic studies in cell culture and functional studies in tissues, and suggests that zebrafish are an ideal model system to further interrogate how cells respond to electric fields in physiological contexts.…”

Osmolarity-independent electrical cues guide rapid response to injury in zebrafish epidermis

“…Complementary to our electrical perturbation experiments in vivo, electric fields have been directly measured in many tissues during regeneration on long timescales (hours and days), and the guiding effects of electric fields on cells in culture have been investigated at short timescales (tens of minutes) (Allen et al, 2013;Iglesia and Vanable, 1998;Li et al, 2012;Nawata, 2001;Zhao et al, 2006). Electric stimulation has been explored numerous times in clinical treatments for wounds and ulcers, but the lack of a detailed understanding of the mechanism by which electric fields influence cell behavior has limited progress (Gentzkow et al, 1991;Zhao et al, 2020). Our direct observation of actin polarization in response to electric fields in vivo at rapid timescales of 5-10 minutes bridges the gap between detailed mechanistic studies in cell culture and functional studies in tissues, and suggests that zebrafish are an ideal model system to further interrogate how cells respond to electric fields in physiological contexts.…”

Analysis of the Differential Gene and Protein Expression Profiles of Corneal Epithelial Cells Stimulated with Alternating Current Electric Fields

“…The human corneal epithelium contains an active Na + /K + -ATPase transport system, with an inward flow of sodium ions and active outward transport of Cl − ions across the stroma and epithelium, establishing a trans-epithelial potential difference. Wounding disrupts this potential difference and consequently leads to the flow of Na + and K + into the wound from the surrounding tissue, generating a laterally orientated physiological EF that can direct orientation and migration of corneal epithelial cells and enhance the epithelial wound healing rate by controlling the division axis in epithelial cells [6,7].…”

“…However, in certain cell types, the application of DC EFs has been shown to negatively affect cell viability and proliferation when compared to alternating current (AC) EFs [18,19], suggesting cell survival benefits of AC EFs [20]. Furthermore, it is known that the exposure of cells to AC EFs significantly enhances intracellular calcium signaling and also alters various cellular functions [7,21,22]. DC is the continuous unidirectional flow of charged particles, which results in electrode polarity.…”