Controlling neural cell behavior with electric field stimulation across a conductive substrate
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Electrical stimulation of tissues induces cell alignment, directed migration, extended processes, differentiation, and proliferation, but the mechanisms involved remain largely unknown. To reveal effects of electric fields (EF) through the media on cell behavior, voltage (7.45 – 22 V), current density (36 – 106 mA/cm2), duration (2 – 24 hrs), and alternating currents (AC, 2 – 1000 Hz) were varied independently when exposed to cell cultures. It was determined that current density and duration are the primary attribute Schwann cells respond to when an EF is applied through the media. This implies that the number of charges moving across the cell surface may play a key role in EF-induced changes in cell behavior. Identical conditions were used to stimulate cells grown on the surface of a conductive substrate to examine if a scaffold can provide structural and EF cues. The effects of an EF through the substrate were examined by placing a protein gel on the surface during stimulation and observing the morphology of subsequent cell cultures and the physical topology of the gel. EFs were shown to create Ca2+ redistribution across gels and subtle changes in collagen I fibril banding. Stimulated gels were able to induce perpendicular Schwann cell alignment on newly seeded cultures days after initial EF exposure, and the cell response decreased when seeded at longer times, indicating the effects of EF on the matrix environment has a relaxation time. These findings were then integrated into a biodegradable, electrically conductive polypyrrole-poly-ε-caprolactone polymer developed by collaborators. Dorsal root ganglia placed in matrix gels on top of conducting polymer exhibited significantly longer axons when stimulated with DC and AC signals. The overall results demonstrate that EFs have a significant effect on the extracellular environment. The broad implication of this data grants researchers with the ability to physically and metabolically control cell behavior with EFs, including improved wound healing or reduced cancer metastasis.