Neural responses to electrical stimulation in 2D and 3D in vitro environments

Electrical stimulation (ES) to manipulate the central (CNS) and peripheral nervous system (PNS) has been explored for decades, recently gaining momentum as bioelectronic medicine advances. The application of ES in vitro to modulate a variety of cellular functions, including regenerative potential, migration, and stem cell fate, are being explored to aid neural degeneration, dysfunction, and injury. This review describes the materials and approaches for the application of ES to the PNS and CNS microenvironments, towards an improved understanding of how ES can be harnessed for beneficial clinical applications. Emphasized are some recent advances in ES, including conductive polymers, methods of charge transfer, impact on neural cells, and a brief overview of alternative methodologies for cellular targeting including magneto, ultrasonic, and optogenetic stimulation. This review will examine how heterogenous cell populations, including neurons, glia, and neural stem cells respond to a wide range of conductive 2D and 3D substrates, stimulation regimes, known mechanisms of response, and how cellular sources impact the response to ES.