Automated Electrical Stimulation Therapy Accelerates Re-Epithelialization in a Three-Dimensional In Vitro Human Skin Wound Model

Authors:
Open Access
Publisher website
Google Scholar
Abstract
Objective: Electrical Stimulation Therapy (EST) shows promise for the purpose of accelerating wound healing, but the right electrical stimulation parameters and its mode of action remain unclear. We aim to evaluate the effect of a new EST clinical device on epidermal repair using an in vitro human skin wound model. Approach: We scaled-up a well-established 3D De-Epidermized Dermis-Human Skin Equivalent (DED-HSE) wound model to fit a clinically used device that delivers pre-programmed microcurrent EST. The impact of EST on re-epithelialization of 4-mm circular epidermal wounds was assessed after 4 and 7 days of treatment, using metabolic activity assay, immunohistochemistry (IHC) staining, and RNA in situ hybridization. Results: EST was successfully applied to the wounded in vitro skin model. Large DED-HSEs retained good cell viability for up to 7 days of EST treatment. Excisional wounds subjected to EST for 4 days consistently exhibited faster closure (mean 65.8%, n=9) compared to untreated wounds (mean 49.7%, n=9) (p<0.05). Wounds exposed to EST exhibited significantly longer epithelial tongues (re-epithelialization mean 50.3%, n=9) than untreated wounds (mean 26.2%, n=9) (p<0.001), suggesting faster keratinocyte migration and proliferation. Increased MMP1 transcription (p<0.05) in ES-treated periwound suggests a mechanism for enhanced keratinocyte migration. IHC staining showed advanced epidermal proliferation (p63) and differentiation (K10) in EST-exposed wounds (n=15), as well as stronger attachment of the newly formed epidermis into the dermis compared to untreated controls (n=15) (p<0.001). Innovation: We present a novel approach to assess an EST clinical device designed to stimulate wound healing. Using a scaled-up 3D human skin wound model, we could demonstrate the positive effect of EST on epithelial cell responses and shed light on possible mechanism. Conclusion: Our study provides experimental evidence that microcurrent therapy accelerates wound closure and improves the quantity and quality of re-epithelialization.

This publication has 58 references indexed in Scilit: