Electrical Stimulation and Cellular Behaviors in Electric Field in Biomedical Research

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.

Keywords: biophysical stimuli; conductive polymer; electrical stimulation; electrode; in vitro.

Figure 1

(A) EF between two electrodes immersed in cell culture, in which the electrodes may take different forms such as L and against the bottom to make the EF more uniform; (B) Using salt bridges between electrodes to avoid the diffusion of electrochemical reaction products into culture medium; (C) Working electrodes as a cell culture substrate in a three-electrode system, where the working electrode can be a metal, a glass slide coated with indium tin oxide, or a conducting polymer.

Figure 2

Conductive substrate mediated ES where the cells are cultured on the substrate and exposed to the potential gradient on substrate surface.

Figure 3

Cells and PPy or its composite served as electrodes and substrates used for electrical stimulation. PPy sheets or PPy membranes synthesized by electrochemical/chemical methods present higher conductivity compared to the PPy composites. (PCL: polycaprolactone, PLLA: poly-L-lactide, PDLA: poly-D-L-lactide).

Figure 4

Two designs offering noninvasive ES. (A) ES through EMF, where a cell culture plate is placed inside a Helmholtz coil in parallel to the direction of MF, or in perpendicular to the direction of MF between two Helmholtz coils; (B) ES through capacitive coupling where a culture plate is sandwiched between two paralleled plates (note: the distance between plates and culture should be minimum to reduce resistance).