Improvement of Human Keratinocyte Migration by a Redox Active Bioelectric Dressing

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.

Analytical Solutions to the Steady State Poisson-Nernst-Planck Equations in Electrobiochemical Systems

“…Such a situation can arise for example under open circuit conditions in a battery (Torabi & Aliakbar, 2012;Venkatraman & Van Zee, 2007), or in a 1-D analog of a bioelectric dressing in contact with water or wound exudate (Banerjee et al, 2014). Furthermore, suppose that there is a constant generation of species n at one of the electrodes, such as the generation of OHions at the oxide surface of a silver oxide electrode (Torabi & Aliakbar, 2012).…”

“…In the present case of a bioelectric dressing however, φ ref is taken to be specified, e.g. the open circuit potential difference across the silver oxide and zinc dots in the bioelectric dressing is on the order of 0.1 V (Banerjee et al, 2014) …”

“…When the dressing contacts wound exudate, redox reactions occur at the electrode surfaces that result in potential differences between silver and zinc dots (Banerjee et al, 2014). This results in an applied electric field distribution that drives electrotaxis and accelerates wound closure.…”

“…Despite the fact that these equations have been well known and studied for over a century, they remain of current interest because of applications ranging from batteries (Torabi & Aliakbar, 2012;Venkatraman & Van Zee, 2007), bioelectric dressings used in wound healing (Banerjee et al, 2014), diffusion of charged species through ion channels in cell membranes and ion selective membranes (Coalson & Kurnikova, 2005;Fíla & Bouzek, 2003), electro-osmosis in micro and nano-channel systems (Hrdlička, Červenka, Přibyl, & Šnita, 2010), transport of charge carriers in semiconductors (Markowich, 1986), ionic current rectification through charged micro and nano channels (Chein & Chung, 2013) to as diverse a field as deterioration of reinforced concrete structures due to diffusion and attack by the chloride ion (K. Krabbenhøft, & J. Krabbenhøft, 2008). In their most general form (unsteady, 3-D), the PNP equations are usually solved numerically.…”

“…2;2015 for the diffusivity inferred from migration experiments because of neglect of the need for quasi-neutrality (K. Krabbenhøft, & J. Krabbenhøft, 2008). In this paper, we consider a benchmark problem pertaining to electrobiochemical systems, specifically bioelectric dressings used in wound healing (Banerjee et al, 2014), which involve the two-species, steady-state PNP equations in 1-D and 2D. Approximate solutions to these equations are obtained using order of magnitude analysis and the singular perturbation method for the 2-D case.…”