Electrical Stimulation of Wound Healing: A Review of Animal Experimental Evidence

Abstract

Significance: Electrical stimulation (ES) is a therapeutic intervention that may help specialists facilitate wound healing rates. The purpose of this section is to compile the available animal research regarding the effectiveness of ES on the injury potential, healing rate, cellular and molecular proliferation, mechanical properties, and survival rate of skin flaps. Recent Advances: Regardless of the type of ES current and polarity used, most of the animal experimental evidence suggests that application of ES can facilitate wound healing. However, treatment time should be sufficiently long to attain good mechanical strength of regenerated tissue, because tensile strength is not consistent with augmented collagen deposition. ES improves the survival rate and skin blood flow of animal flaps, but clinical studies are needed to substantiate the findings from these animal experiments. Critical Issues: Impaired or delayed healing is a major clinical problem that can lead to wound chronicity. ES with various strategies has been used to facilitate the healing process, but many aspects remain controversial. Despite much research, no consensus exists regarding the detailed effects of ES on wound healing. Nevertheless, ES has been approved by the Center for Medicare and Medicine Services for reimbursement of the treatment of some chronic ulcers. Future Directions: Exogenous ES may promote the directional migration of cells and signaling molecules via electrotaxis; however, its underlying mechanism is still poorly understood. Future studies that further elucidate the mechanisms regulating electrotaxis will be necessary to optimize the use of ES in different wound states.

Giti Torkaman, PhD

Figure 1.

Block diagram of differential amplifier equipment to measure differential skin surface potential. Two surface electrodes (EL 1 and EL 2) are placed on the wound site and near skin intact area; these electrodes can be movable at specific locations. A single fixed reference electrode (Ref) is placed on the intact skin away from the two recording electrodes. Differential skin surface potential measuring technique is a non-invasive method to record endogenous potential without using any inserted electrodes.

Figure 2.

The value of skin potential before, immediately after incision, and during healing period in a guinea pig full-thickness wound. Control: without electrical stimulation (ES) application, anodal and cathodal: with application of ES (was recorded by author).

Figure 3.

Various waveforms of pulsed ES that are used in animal studies, including (A) high voltage, (B) monophasic, (C) balanced biphasic, (D) unbalanced biphasic, and (E) biphasic sine wave or alternative current.

Figure 4.

Proposed mechanisms of ES on mast cells in wound healing process.

Figure 5.

Schematic illustration showing the effect of ES on wound closure.

Figure 6.

Light micrograph (hematoxylin and eosin, 100×) of full-thickness wound in guinea pig 7 days after incision: left, control; middle, cathodal ES; right, anodal ES. Cathodal and anodal direct current (DC) ES (sensory intensity) was applied for 1 h per day, every other day, for 7 days. The number of fibroblasts (dark fusiform cells, F) was significantly higher in cathodal ES group compared with control group. (Unpublished data were recorded by author.)

Figure 7.

A schematic illustration of stress–strain curve to measure the mechanical strength of wound site. Ultimate stress is force/cross-section area, and strain is percent of tissue deformation.

Figure 8.

Schematic illustration shows the effect of ES on the mechanical strength of wounds.

Figure 9.

Effective elements to increase the blood flow and flap viability after the application of ES. Release of some vasodilating neuropeptides such as substance P (SP) calcitonin gene-related peptide (CGRP), and vasoactive intestinal polypeptide (VIP), or the release of opioids, especially after low-frequency ES may be effective to increase blood flow and flap viability. In addition, muscle pumping may increase blood flow when stimulation is performed at the motor level.