Abstract
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.
Highlights
After Italian physician Luigi Galvani first noticed the leg movement of brain-dead frogs following an exposure to electricity, the electrical properties of tissues and cells have been extensively studied, leading to the formation and maturity of the entire domain of electrophysiology
The proliferation and morphology of human carcinoma cells MKN45 cultured on the surface of a platinum-coated plastic plate electrode were altered depending on the applied potential [36], with the cell proliferation halted when the potential was above 0.4 V vs. the reference electrode Ag/AgCl
Duty cycles of 10%, 30%, 50%, 80%, and 100% (DC) were used. They found that the electromagnetic field (EMF) generated by narrow (10%) pulses significantly reduced the number of the neurite bearing cells and the number of neurites extended along the direction of the EMF, but increased the average length of the neurites
Summary
After Italian physician Luigi Galvani first noticed the leg movement of brain-dead frogs following an exposure to electricity, the electrical properties of tissues and cells have been extensively studied, leading to the formation and maturity of the entire domain of electrophysiology. While electrophysiology is a highly developed area with a long history, electroactivity as an intrinsic property of human tissues and an important phenomenon in tissue regeneration and wound healing has not been widely recognized among material scientists. This is clearly testified by the reported biomaterials that are mostly insulators, and by the large absence of electricity as a tool in regenerative medicine. As all players in this recognition process, including ECM, solvent molecules, antibodies, and antigen-presenting entities, are sensitive to electric field (EF), owing to the charges and polar groups in their molecules, the distribution and movement of these players, among other properties, can be manipulated or influenced by either endogenous or exogenous EF, theoretically at least, leading to the electrical modulation of cellular interactions. As we feel methods are the key to perform such studies, this review is organized according to the experimental setups and the materials used to mediate ES
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