Angiogenesis is induced and wound size is reduced by electrical stimulation in an acute wound healing model in human skin.
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.
Plastic & Reconstructive Surgery Research, Manchester Institute of Biotechnology, University of Manchester, Manchester, United Kingdom; University Hospital of South Manchester NHS Foundation Trust, Institute of Inflammation and Repair, Faculty of Medical and Human Sciences, University of Manchester, Manchester Academic Health Science Centre, Manchester, United Kingdom.
Sara
S
Ud-Din
Plastic & Reconstructive Surgery Research, Manchester Institute of Biotechnology, University of Manchester, Manchester, United Kingdom.
Anil
A
Sebastian
Oxford Bioelectronics, Innovation Centre, Abingdon, United Kingdom.
Pamela
P
Giddings
Oxford Bioelectronics, Innovation Centre, Abingdon, United Kingdom.
James
J
Colthurst
Medical Statistics, University Hospital South Manchester, Manchester, United Kingdom.
Sigrid
S
Whiteside
Medical Statistics, University Hospital South Manchester, Manchester, United Kingdom.
Julie
J
Morris
BioElectroMed Corporation, Burlingame, CA, United States of America.
Richard
R
Nuccitelli
Department of Cell Physiology and Pharmacology, University of Leicester, Leicester, United Kingdom.
Christine
C
Pullar
University Hospital of South Manchester NHS Foundation Trust, Institute of Inflammation and Repair, Faculty of Medical and Human Sciences, University of Manchester, Manchester Academic Health Science Centre, Manchester, United Kingdom.
Mo
M
Baguneid
Plastic & Reconstructive Surgery Research, Manchester Institute of Biotechnology, University of Manchester, Manchester, United Kingdom; University Hospital of South Manchester NHS Foundation Trust, Institute of Inflammation and Repair, Faculty of Medical and Human Sciences, University of Manchester, Manchester Academic Health Science Centre, Manchester, United Kingdom; Centre for Dermatology Research, Institute of Inflammation and Repair, University of Manchester, Manchester, United Kingdom.
Ardeshir
A
Bayat
D000328:Adult; D004558:Electric Stimulation / Q000379:methods*; D005260:Female; D064368:Healthy Volunteers; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D018919:Neovascularization, Physiologic / Q000502:physiology*; D060888:Real-Time Polymerase Chain Reaction; D012867:Skin / Q000503:physiopathology*; D014945:Wound Healing / Q000502:physiology*; D055815:Young Adult