Endogenous Bioelectrics in Development, Cancer, and Regeneration: Drugs and Bioelectronic Devices as Electroceuticals for Regenerative Medicine

Abstract

A major frontier in the post-genomic era is the investigation of the control of coordinated growth and three-dimensional form. Dynamic remodeling of complex organs in regulative embryogenesis, regeneration, and cancer reveals that cells and tissues make decisions that implement complex anatomical outcomes. It is now essential to understand not only the genetics that specifies cellular hardware but also the physiological software that implements tissue-level plasticity and robust morphogenesis. Here, we review recent discoveries about the endogenous mechanisms of bioelectrical communication among non-neural cells that enables them to cooperate in vivo. We discuss important advances in bioelectronics, as well as computational and pharmacological tools that are enabling the taming of biophysical controls toward applications in regenerative medicine and synthetic bioengineering.

Organic Bioelectronics: Using Highly Conjugated Polymers to Interface with Biomolecules, Cells, and Tissues in the Human Body

“…The emergent behavior of this nonlinear feedback system is complex and still being understood. [ 49,50 ] For the interested, we recommend a number of reviews for a more in‐depth discussion of the current state of understanding of these mechanisms. [ 48,51,52 ]…”

“…Developing new bioelectric gradient models and scaffolds can potentially support studies into the role of bioelectricity and influence fundamental development behaviors. [ 48,49 ]…”

Role of Bioelectricity During Cell Proliferation in Different Cell Types

“…Bioelectricity originates at the cell membrane from a constant imbalance in charge between the intra-and extracellular compartments, caused by the passage of ions (Na + , K + , Ca 2+ , Cl − , etc..) through different types of ion pumps and channels. The different distribution of these ions on either side of the cell membrane results in intra-and extracellular voltage differences, known as membrane potential or V mem (Levin et al, 2019). Such a balance is maintained via passive and active ion transport through various ion channels and transporters located within the membrane (Sundelacruz et al, 2009).…”

“…V mem is expressed relative to the extracellular environment so that a cell is "depolarized" when its V mem is less negative, while a cell is "hyperpolarized" when its V mem is more negative (Cervera et al, 2016;Erndt-Marino and Mariah, 2016). Accordingly, V mem values of rapidly proliferating embryonic and tumor cells, generally have high "depolarized" V mem values, whereas nonproliferating, terminally differentiated somatic cells, such as, skeletal muscle cells, neurons and fibroblasts typically have low "hyperpolarized" V mem values as shown in Figure 1 (Binggeli and Weinstein, 1986;Chernet and Levin, 2013;Levin et al, 2019;Sundelacruz et al, 2019).…”

“…through different types of ion pumps and channels. The different distribution of these ions on either side of the cell membrane results in intra- and extra-cellular voltage differences, known as membrane potential or V mem (Levin et al, 2019 ). Such a balance is maintained via passive and active ion transport through various ion channels and transporters located within the membrane (Sundelacruz et al, 2009 ).…”