Skin wounds that are slow to heal are a clinical challenge to physicians all over the world. Every year, the NHS alone spends £1 billion on treating chronic wounds such as lower limb venous and diabetic ulcers. Wounds become chronic when they fail to heal and remain open for longer than six weeks.
Researchers from The University of Manchester carried out the unique human volunteer study of skin wound healing in 40 individuals with the results published in the journal PLOS ONE.
An untreated wound (left) after 10 days is larger than an electrical-stimulation-treated wound (right) (credit: The University of Manchester)
In the new research, half-centimetre, harmless wounds were created on each upper arm of the volunteers. One wound was left to heal normally while the other was treated with electrical pulses over a period of two weeks. These pulses stimulated the process through which new blood vessels form – known as angiogenesis – increasing the blood flow to the damaged area and resulting in the wounds healing significantly faster.
Now, the researchers at the University’s Institute of Inflammation and Repair led by Dr Ardeshir Bayat are to work with Oxford BioElectronics Ltd on a five-year project to develop and evaluate devices and dressings which use the same techniques to stimulate the body’s nervous system to generate nerve impulses to the site of skin repair.
Dr Ardeshir Bayat, the principal investigator from the University, is also leading on the partnership. He said: “This research has shown the effectiveness of electrical stimulation in wound healing, and therefore we believe this technology has the potential to be applied to any situation where faster wound healing is particularly desirable, such as following human or veterinary surgical wounds, accidental, or military trauma and in sports injuries.”
Abstract of 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, surface area was reduced on days 10 and 14 and wound diameter reduced on days 10 and 14. Blood flow increased significantly post-ES on D10 and 14. Angiogenic markers were up-regulated following ES application; protein analysis by IHC showed an increase 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 in PLGF on days 7 and 14 (51% and 35% respectively). WB studies showed a significant increase of 30% 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.