Pulsed Asymmetric Biphasic Electrical Fields Accelerate Peripheral Nerve Regeneration into Split-Thickness Skin Graft Donor Sites.

Abstract

Split-thickness skin grafts are an effective therapy for treating large skin wounds; however, patients may experience chronic pain and dysesthesia from poor regeneration of sensory nerves into the harvest site. Endogenous and exogenous electrical fields are known to direct axon regeneration and support epithelial wound healing. This study aimed to demonstrate the efficacy of a novel therapeutic electrical stimulation protocol, asymmetric charge-balanced (ACB) waveforms, to aid in peripheral nerve regeneration and wound healing. Split-thickness skin harvests were collected from 4 Thy1-GFP rats, with each rat receiving 2 harvests. After this, rats received electrical stimulation on 1 of their wounds for 5 days using ACB waveforms. After the animals were killed, the harvest sites were collected, and fluorescence levels were quantified using ImageJ software. Split-thickness skin harvests were collected from 4 Long-Evans rats that were stimulated for 5 days using ACB waveforms. Equivalent wound resistance was characterized to quantify the rate of wound healing. Increased peripheral nerve regeneration was observed in the split-thickness skin harvest sites of the stimulated group compared with the control group. Impedance measurements showed significantly increased impedance in wounds that underwent stimulation compared with sham controls, suggesting accelerated wound healing in the stimulated group. The authors' work suggests a potential noninvasive strategy, translatable to humans, for enhancing healing of split-thickness skin harvest sites that could minimize associated morbidity. This study shows that pulsed asymmetric biphasic electrical fields regenerate peripheral nerves and accelerate wound healing in split-thickness skin graft donor sites, offering a promising approach to reduce chronic pain, hyperesthesia, and pruritus, while restoring normal sensation to patients.