“Pulsed Asymmetric Biphasic Electrical Fields Accelerate Peripheral Nerve Regeneration into Split Thickness, Skin Graft Donor Sites”

Background: 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 electric fields (EFs) 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. Methods: Split-thickness skin harvests were collected from four Thy1-GFP rats, with each rat receiving two harvests. Following this, rats received electrical stimulation on one of their wounds for five days using ACB waveforms. After euthanasia, the harvest sites were collected, and fluorescence levels were quantified using ImageJ software. Split-thickness skin harvests were collected from four Long-Evans rats that were stimulated for five days using ACB waveforms. Equivalent wound resistance was characterized to quantify the rate of wound healing. Results: Increased peripheral nerve regeneration was observed in the split-thickness skin harvest sites of the stimulated group compared to control. Impedance measurements showed significantly increased impedance in wounds that underwent stimulation compared to sham controls, suggesting accelerated wound healing in the stimulated group. Conclusion: Our work suggests a potential non-invasive strategy, translatable to humans, for enhancing healing of split-thickness skin harvest sites that could minimize associated morbidity.