Electrochemically stimulating developments in bioelectronic medicine

Abstract

Cellular homeostasis is in part controlled by biological generated electrical activity. By interfacing biology with electronic devices this electrical activity can be modulated to actuate cellular behaviour. There are current limitations in merging electronics with biology sufficiently well to target and sense specific electrically active components of cells. By addressing this limitation, researchers give rise to new capabilities for facilitating the two-way transduction signalling mechanisms between the electronic and cellular components. This is required to allow significant advancement of bioelectronic technology which offers new ways of treating and diagnosing diseases. Most of the progress that has been achieved to date in developing bioelectronic therapeutics stimulate neural communication, which ultimately orchestrates organ function back to a healthy state. Some devices used in therapeutics include cochlear and retinal implants and vagus nerve stimulators. However, all cells can be impacted by electrical inputs which gives rise to the opportunity to broaden the use of bioelectronic medicine for treating disease. Electronic actuation of non-excitable cells has been shown to lead to 'programmed' cell behaviour via application of electronic input which alter key biological processes. A neglected form of cellular electrical communication which has not yet been considered when developing bioelectronic therapeutics is faradaic currents. These are generated during redox reactions. A precedent of electrochemical technology being used to modulate these reactions, thereby controlling cell behaviour, has already been set. In this mini review we highlight the current state of the art of electronic routes to modulating cell behaviour and identify new ways in which electrochemistry could be used to contribute to the new field of bioelectronic medicine.

Keywords: Bioelectrochemistry; Bioelectronic interfaces; Cellular signalling; Nanobioelectronics.

Fig. 1

Bulk ion vs faradaic conductance across the cell plasma membrane. Ionic currents are produced by the movement of charges across the membrane through the ionic channels, whereas faradaic currents are produced by the movement of electrons between electrochemical mediators

Fig. 2

Schematic representation of a bioelectronic approach at targeting the vagus nerve to control inflammation. Vagus nerve signalling interacts with the splenic nerve that reaches splenic T cells that produce acetylcholine, which reduces inflammation

Fig. 3

Different biological functions can be triggered by the application of electric fields and these include actuating cell movement, modulating the cell cycle which benefits wound healing and tissue regeneration. Currents can polarise a) single cells and b) tissues. Black arrows indicate the direction of the electrical currents whereas red arrows indicate the direction of the resulting polarised behaviour (Chang and Minc 2014)

Fig. 4

Transduction of signals on a bioelectrochemical system. An electronic input in the form of potential modulates the redox state of naturally occurring electrochemical mediators, from an inactive state to an active state or vice versa, and are communicated to a cellular system triggering biological response (Tschirhart et al. 2017)