Abstract

Angiogenesis is critical for wound healing. Insufficient angiogenesis can result in impaired wound healing and chronic wound formation. Electrical stimulation (ES) has been shown to enhance angiogenesis. We previously showed that ES enhanced angiogenesis in acute wounds at one time point (day 14). The aim of this study was to further evaluate the role of ES in affecting angiogenesis during the acute phase of cutaneous wound healing over multiple time points. We compared the angiogenic response to wounding in 40 healthy volunteers (divided into two groups and randomised), treated with ES (post-ES) and compared them to secondary intention wound healing (control). Biopsy time points monitored were days 0, 3, 7, 10, 14. Objective non-invasive measures and H&E analysis were performed in addition to immunohistochemistry (IHC) and Western blotting (WB). Wound volume was significantly reduced on D7, 10 and 14 post-ES (p = 0.003, p = 0.002, p<0.001 respectively), surface area was reduced on days 10 (p = 0.001) and 14 (p<0.001) and wound diameter reduced on days 10 (p = 0.009) and 14 (p = 0.002). Blood flow increased significantly post-ES on D10 (p = 0.002) and 14 (p = 0.001). Angiogenic markers were up-regulated following ES application; protein analysis by IHC showed an increase (p<0.05) in VEGF-A expression by ES treatment on days 7, 10 and 14 (39%, 27% and 35% respectively) and PLGF expression on days 3 and 7 (40% on both days), compared to normal healing. Similarly, WB demonstrated an increase (p<0.05) in PLGF on days 7 and 14 (51% and 35% respectively). WB studies showed a significant increase of 30% (p>0.05) on day 14 in VEGF-A expression post-ES compared to controls. Furthermore, organisation of granulation tissue was improved on day 14 post-ES. This randomised controlled trial has shown that ES enhanced wound healing by reduced wound dimensions and increased VEGF-A and PLGF expression in acute cutaneous wounds, which further substantiates the role of ES in up-regulating angiogenesis as observed over multiple time points. This therapeutic approach may have potential application for clinical management of delayed and chronic wounds.

Highlights

  • Angiogenesis is a critical component for processes in wound healing and is defined as the formation of new capillaries from pre-existing blood vessels [1, 2]

  • The non-invasive clinical results will be presented in relation to wound surface area, wound volume, wound diameter, wound depth and blood flow

  • At day 10 wound surface area in the control arm was generally higher with median of 9.21; whereas for the post-Electrical stimulation (ES) arm surface area measurements were significantly lower with median of 7.22 (p = 0.001)

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Summary

Introduction

Angiogenesis is a critical component for processes in wound healing and is defined as the formation of new capillaries from pre-existing blood vessels [1, 2]. Electrical stimulation (ES) in its various forms has been shown to enhance wound healing by promoting the migration of keratinocytes and macrophages, enhancing angiogenesis, stimulating fibroblasts, and influencing protein synthesis throughout the inflammatory, proliferative and remodelling phases of healing [9,10,11]. Electrical signals have been shown to stimulate angiogenesis and organise blood vessel formation [3]. Endogenous electric fields are able to direct the migration of epithelial cells during wound healing and may contribute to regulation of angiogenesis [14]

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