Improvement of Human Keratinocyte Migration by a Redox Active Bioelectric Dressing

Jaideep Banerjee,Prerna Suri,Christopher J Chang,Bryan C Dickinson,Chandan K Sen,Emily K Sequin,Karen Bellman,Sashwati Roy,Savita Khanna,Vish V Subramaniam,Piya Das Ghatak

doi:10.1371/journal.pone.0089239

Abstract

Exogenous application of an electric field can direct cell migration and improve wound healing; however clinical application of the therapy remains elusive due to lack of a suitable device and hence, limitations in understanding the molecular mechanisms. Here we report on a novel FDA approved redox-active Ag/Zn bioelectric dressing (BED) which generates electric fields. To develop a mechanistic understanding of how the BED may potentially influence wound re-epithelialization, we direct emphasis on understanding the influence of BED on human keratinocyte cell migration. Mapping of the electrical field generated by BED led to the observation that BED increases keratinocyte migration by three mechanisms: (i) generating hydrogen peroxide, known to be a potent driver of redox signaling, (ii) phosphorylation of redox-sensitive IGF1R directly implicated in cell migration, and (iii) reduction of protein thiols and increase in integrinαv expression, both of which are known to be drivers of cell migration. BED also increased keratinocyte mitochondrial membrane potential consistent with its ability to fuel an energy demanding migration process. Electric fields generated by a Ag/Zn BED can cross-talk with keratinocytes via redox-dependent processes improving keratinocyte migration, a critical event in wound re-epithelialization.

Highlights

The presence of electric fields and natural direct currents, in the vicinity of regenerating limbs, driven by so-called ‘skin batteries’, is essential for normal regeneration, and their reversal induces degeneration [1,2]
Electric fields have been reported to direct cell migration in many different cell types [11,13,14], activate signaling pathways such as cdc42p, Rho/Rac, PI3K/PTEN and phosphatidylinositol (PIP) [11,15,16,17], activation of epithelial sodium channels [18], cellular electrotaxis of macrophages [19,20], neutrophils [19,21] and fibroblasts
We provide the first evidence characterizing a novel FDA approved silver-zinc coupled bioelectric dressing (BED) which is currently being used in clinical wound care

Summary

Introduction

The presence of electric fields and natural direct currents, in the vicinity of regenerating limbs, driven by so-called ‘skin batteries’, is essential for normal regeneration, and their reversal induces degeneration [1,2]. We provide the first evidence characterizing a novel FDA approved silver-zinc coupled bioelectric dressing (BED) which is currently being used in clinical wound care. The advantage of this device is that it is wireless and has no need for an external power source, can be cut to the size of the wound and conforms to irregular surfaces and provides an electrical field in the range of the physiologic fields [33,34] found at healing wound edges. To develop a mechanistic understanding of how the BED may potentially influence wound re-epithelialization, a key event in wound healing, we directed emphasis on understanding the influence of BED on human keratinocyte cell migration

Methods

Results

Conclusion