Eradication of Wound Biofilms by Electrical Stimulation - Antibiofilm Agents: From Diagnosis to Treatment and Prevention - page 420

3.3 In Vivo Studies Examining Electrical Stimulation

and Wound Healing

In vivo studies on the effects on ES on cell migration have discovered significant
benefits: a study by Eberardt et al. found a 24 % increase in neutrophils from human
wounds stimulated by exogenous ES currents (Eberhart and Korytowski 1986 ),
while a study by Mertz et al. ( 1993 ) on epidermal cell migration in response to ES
demonstrated 20 % greater wound epithelialization in an ovine model. Several
models have been proposed as to how ES aids cell migration in vivo by
galvanotaxis. Movement of proteins embedded in the plasma membrane may
occur when cells are exposed to an electric field; for example, epidermal growth
factor receptors have been shown to move to the cathode side of keratinocytes in a
LIDC electric field (Fang et al. 1999 ). Other affected regions that ES may stimulate
to initiate galvanotaxis include membrane depolarizations due to calcium ion flow
(Bedlack et al. 1992 ), changes in cell form and cytoskeleton (Soong et al. 1990 ;
Onuma and Hui 1985 , 1986 ; Luther et al. 1983 ), and protein kinase activity (Baker
and Peng 1993 ; Peng et al. 1993 ). Weak electric fields used for galvanotaxis of cells
in culture or clinically used currents for enhancement of healing of chronic wounds
may replicate the natural electric fields found in mammalian wounds (Nishimura
et al. 1996 ; Sheridan et al. 1996 ). These differential galvanic effects should be used
to plan the therapeutic treatment based on selection of the anode or cathode at
various time points for the greatest ES benefit. Although the effect of ESTHR can
be explained to some extent by stimulating host cells, there appear to be other
mechanisms important to enhance wound healing. The remainder of this chapter
will focus on the three primary forms of ESTHR, first including relevant clinical
studies and then examining studies on the specified electrical stimulation and
bacterial biofilms.

4 Low-Intensity Direct Current Background

Direct current (DC) (sometimes referred to as galvanic or continuous current) is a
form of electrical current which constantly flows in only one direction
(monophasic) and is generated by thermocouples, batteries, and solar cells. LIDC
refers to the continuous form of DC (Fig. 1A ) and is applied at intensities ranging
from 20 A to 32 mA (Feedar et al. 1991 ). LIDC was the first form of electrotherapy

explored as a wound care adjunctive therapy (Carey and Lepley 1962 ) and, not
surprisingly, remains as the most commonly researched low-intensity current
(Balakatounis and Angoules 2008 ). In 1962 LIDC was explored in an animal
wound model and was found to enhance wound healing and stimulate the immune
response (Carey and Lepley 1962 ). Shortly thereafter, clinical trials further dem-
onstrated LIDC's potency to significantly enhance wound healing.

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