Medical Science
April 7, 2021

Bioelectrical Stimulation: An Introduction To The Future of Wound Care

Woundtech Science & Info Team
Woundtech Science & Info Team

Bioelectrical Stimulation: An Introduction To The Future of Wound Care

Co-authored by Professor Ardeshir Bayat BSc (Hons) MB BS PhD & Chloe Stockwell Clark BSC (Hons), Biology, Cell

Wound management remains a contentious challenge in the clinical sector, impacting top tier medical systems and significantly increasing the overall cost of medical care. The sector has cost the UK NHS an estimated £8.3 billion per year, of which £2.7 billion and £5.6 billion were associated with managing healed and unhealed wounds, respectively. Reports show 81% of the total annual NHS cost was incurred within the community setting. This equates to 3.8 million patients annually presenting with some form of wound(1). Despite recent advances in the wound care sector, there is still an unmet need for a treatment modality capable of improving both the rate and quality of wound healing. The integration of such wound care technology would significantly benefit the wider health economy, patient recovery and overall quality of care. 

Phases and treatment modalities for wound healing

After tissue damage, wound healing follows a series of physiological events. The phases of wound healing include; hemostasis, inflammation, proliferation, and remodeling. Patients’ healing response time may vary due to local and systemic factors such as the ones listed below:

Local and systemic factors that can impact patients' healing time response
The wound care needs of patients can be complex and requires a coordinated, multidisciplinary, team-based approach which uses different scientific and technological modalities.

Clinical pathways of wound management may involve; metabolic control, debridements, wound care products, antibiotics, reconstructive and/or vascular intervention, hyperbaric oxygen treatments and electrical stimulation. Involvement of the patient in the treatment with the help of new therapeutic approaches is an important part of the wound management process. 

The Role of Electrical Stimulation

Electrical stimulation (ES) treatment modality is gaining interest and popularity amongst health professionals due to its convenient, non-invasive and drug-free nature. As a result, ES is becoming more established within different healthcare settings including; primary care, secondary/clinical care and home care environments. It is a highly accessible technology in terms of cost and practical application, whilst being indicated for wounds of various aetiologies. 

Man being treated by nurse to recover from wound injury
The key areas of wound care where ES could have the largest impact are:
  • Chronic Wound Healing - Facilitated healing for chronic wounds including diabetic foot ulcers, vascular ulcers, burns, pressure wounds etc. 
  • Acute Wound Healing - Accelerated healing for post-operative surgical sites, soft tissue injuries and common wounds.
  • Prevention -It is predicted that ES improves the causes and consequences of chronic wound formation on the skin. It is used for diabetic neuropathy with or without impaired circulation, vascular diseases (venous or arterial), and immobility patients who are at risk of decubitus ulcers. 
How are Electrical Stimulation Formulations Developed?

The complex series of wound healing processes and cascades on both cellular and systemic levels have been well established. More recently, it has become evident that when ES is applied similarly to naturally occurring bioelectrical activity of tissues and cells, it can be beneficial to the biomolecular mechanisms needed to support and facilitate the underlying healing processes. In response, advanced ES can be formulated and optimised specifically for the purpose of facilitating wound healing. 

Electrical stimulation in use on leg injury

Research and published literature on the application of ES for wound healing have uncovered a range of parameters that elicit particular physiological responses that are advantageous and supportive of the different stages of healing. Therefore, it is essential that ES used for wound healing has been formulated using parameters known to be specifically beneficial for wound healing, over other basic or generic waveforms. In order to incorporate all waveform parameters and optimise ES application, it is best practice for the treatments to be formulated and preprogrammed into software that delivers the optimised treatments of ES without the need for manual adjustment or manipulation of the current being applied. As a result, high efficacy, user friendly and relatively low-cost ES wound care technology can be harnessed and readily available for clinician and patient use. 

Example of bioelectronics being utilised by a clinician
It is essential that ES used for wound healing has been formulated using parameters known to be specifically beneficial for wound healing, over other basic or generic waveforms
Microcurrent Stimulation (MCS):

For the application of ES for wound healing, Microcurrent Stimulation (MCS) is used to provide electrical current that is most similar to endogenous bioelectrical activity of cells and tissues, and has been shown to facilitate the biomolecular processes involved in wound healing and tissue repair. 

When developing and formulating effective microcurrent waveforms, some of the key parameters include; 

  • Waveform Shape e.g. square, rectangular, sinusoidal.
  • Current Type e.g. direct, pulsed or alternating current.
  • Polarity e.g. biphasic or monophasic. The polarity of the electrical current is a significant factor in healing, with negative and positive polarities being beneficial at different stages of the healing process(2).   
  • Amplitude e.g. Wound healing amplitudes range between 0-500 microamps (µA). 
  • Frequency Ranges used are often between 0.5 - 500 Hertz (Hz). 
  • Pulse e.g. Duration/width, spacing and burst patterns. 
An example of a microcurrent waveform: Square, symmetrical biphasic waveform

Physiological Responses to ES/MCS Stimulation

There are a number of mechanisms of action and physiological responses reported in scientific literature in response to ES/MCS for wound healing. These include;

1. ‘Current of Injury

Wounds that result from trauma or surgery are associated with changes in bioelectric potentials, termed ‘current of injury’(3). This has been observed at the wound site, and plays a key role in the repair process (4). These fields measure an estimated 140 mV/mm and play important roles in controlling several aspects of the cell biology of wound healing(3). 

Wound being treated in clinical setting

In essence, damaged tissues generate the current of injury, which appear to drive elements of the healing response (5-9). Alterations in normal endogenous bioelectricity, due to pathology or trauma, can impact the natural repair process and impair wound healing. There is evidence to suggest that the application of exogenous current across the wound site, facilitates and restores the natural repair process through various mechanisms. This includes; acting as a guidance cue and promoting wound healing (10-11). 

Evidence suggests that the application of exogenous current across the wound site, facilitates and restores the natural repair process.
2. Down-regulation of Inflammation

Regardless of whether the wound is from surgery or trauma, managing inflammation is critical. In some cases, wounds do not progress to the normal healing stage with formation of a final mature scar, but instead remain in the inflammatory process, which can progress to chronic wounds(12). Research has revealed:

3. Angiogenesis

The third physiological response, angiogenesis, is a physiological process that involves the growth of renewed blood vessel formation from the existing vasculature. Cells of metabolically active tissues are a few hundred micrometers away from a blood capillary. Adequate perfusion is essential, and blood vessel capillaries are necessary for ensuring adequate diffusion exchange of nutrients and metabolites in various tissues of the body(17). 

Angiogenesis is a vital component of the processes involved in wound healing(18-19). There is evidence to suggest that inadequate angiogenesis can be conducive to wound healing impairment and chronic wound formation(20-24).

Bai and colleagues (2005) reported that a direct current electrical signal may act as a directional cue and play a role in the spatial organisation of vascular structure(25). Also, it has been observed that electrotherapy can mediate angiogenesis(26-27), which is facilitated by increased expression of vascular endothelial growth factor (VEGF). Moreover, experimental gene and protein investigations are in accordance with these findings by showing up-regulation of angiogenesis and down-regulation of inflammation in electrotherapy treated wounds (28), and also promoting wound healing(29-33).

It is most likely that a combination of different biomolecular responses elicited by ES has enabled enhanced healing in respect to both the rate of healing and quality of the reformed tissue structure.

Summarising Wound Care and Electrical Stimulation

To conclude, scientific literature and a growing body of evidence suggests that bioelectricity plays a key role in the repair process of injured tissue, and provides a robust rationale for the application of exogenous current to promote wound healing(10-11). In response, ES demonstrates a promising and novel therapy application for use in combination with gold standard wound care. Conveniently, ES can be readily applied to different types of wounds, especially where the natural repair mechanism is impaired due to underlying pathology. However, such promising wound care technology is entirely dependent on the application of evidence-based formulations of ES/MCS in order to yield positive and optimized outcomes. 

Read more about how NuroKor’s technology could provide a cost-effective, drug-free alternative to conventional medication. 

About NuroKor:

Founded in 2018, NuroKor is a company committed to the development of bioelectronic technologies. NuroKor develops and formulates programmable bioelectronic software for clinical and therapeutic applications, in a range of easy to use, wearable devices. It provides the highest-quality products, delivering personalised pain relief and recovery support and rehabilitation to patients.

References:
  1. Guest, J., Fuller, G. and Vowden, P., 2020. Cohort study evaluating the burden of wounds to the UK’s National Health Service in 2017/2018: update from 2012/2013. BMJ Open, 10(12), p.e045253.
  2. Ahmed, A., Elgayed, S. and Ibrahim, I., 2012. Polarity effect of microcurrent electrical stimulation on tendon healing: Biomechanical and histopathological studies. Journal of Advanced Research, 3(2), pp.109-117.
  3. McCaig, C. D., Rajnicek, A. M., Song, B. et al. Controlling cell behaviour electrically: Current views and future potential. Physiol Rev. 2005, 85:943–78
  4. Nuccitelli, R. A role for endogenous electric fields in wound healing. Curr. Top. Dev. Biol. 2003, 58:1–26.
  5. Borgens, R.B., Endogenous ionic currents traverse intact and damaged bone. Science, 1984a. 225(4661): p. 478-82.
  6. Borgens, R. B. What is the role of naturally produced electric current in vertebrate regeneration and healing? International Review of Cytology. 1982, 76: 245-298.
  7. Kappel, D., S. Zilber, and L. Ketchum, In vivo electrophysiology of tendons and applied current during tendon healing, in Biologic and clinical effects of low-frequency magnetic and electric fields, J.G. Llaurado, A. Sances, and J.H. Battocletti, Editors. 1974, C C Thomas: Illinois. p. 252-260.
  8. Song, B., M. Zhao, J.V. Forrester, and C.D. McCaig, Electrical cues regulate the orientation and frequency of cell division and the rate of wound healing in vivo. Proc Natl Acad Sci U S A, 2002. 99(21): p. 13577-82.
  9. Vanables, J.W.J., Integumentary potentials and wound healing, in Electric Fields in Vertebrate Repair, R.B. Borgens, et al., Editors. 1984, Alan R Liss Inc: New York.
  10. Kloth LC and McCulloch JM. Promotion of wound healing with electrical stimulation. Adv Wound Care. 1996, 9(5): 42-5.
  11. Ly M, Poole-Warren LA. Acceleration of Wound Healing Using Electrical Fields: Time for a Stimulating Discussion. Wound Practice & Research: Journal of the Australian Wound Management Association. 2008, Vol. 16, No. 3, 138-151
  12. Rosique RG, Rosique MJ, Farina JA. Curbing Inflammation in Skin Wound Healing: A Review. International Journal of Inflammation Volume 2015, Article ID 316235, 9
  13. McMakin CR, Gregory WM, Phillips TM. Cytokine changes with microcurrent treatment of fibromyalgia associated with spine trauma. Journal of Bodywork and Movement Therapies. 2005, 9, 169-176
  14. Lee JW, Yoon SW, Kim TH, Park SJ. The Effects of Microcurrent (MCS) On Inflammatory Reactions Induced by Ultraviolet Irradiation. Journal of Physical Therapy Science. 2011, 23, 693-696. 
  15. Kaur S, Lyte P, Garay M, Liebel F, Sun Y, Liu JC, Southall MD: Galvanic zinc-copper microparticles produce electrical stimulation that reduces the inflammatory and immune responses in skin. Arch Dermatol Res 2011, 303:551–562.
  16. Demir H, Balay H, Kirnap M. A comparative study of the effects of electrical stimulation and laser treatment on experimental wound healing in rats, Journal of Rehabilitation Research & Development. 2004, Volume 41, Number 2, Pages 147–154
  17. Adair TH, Montani JP. Angiogenesis. San Rafael (CA): Morgan & Claypool Life Sciences; 2010.
  18. Greaves NS, Ashcroft KJ, Baguneid M, Bayat A. Current understanding of molecular and cellular mechanisms in fibroplasia and angiogenesis during acute wound healing. J Dermatol Sci. 2013;72: 206–217. Pmid:23958517
  19. Risau W. Mechanisms of angiogenesis. Nature. 1997;386: 671–674. Pmid:9109485
  20. Drinkwater SL, Burnand KG, Ding R, Smith A. Increased but ineffectual angiogenic drive in non-healing venous leg ulcers. J Vasc Surg. 2003;38: 1106–1112. Pmid:14603223
  21. Galiano RD, Tepper OM, Pelo CR, Bhatt KA, Callaghan M, Bastidas N, et al. Topical vascular endothelial growth factor accelerates diabetic wound healing through increased angiogenesis and by mobilizing and recruiting bone marrow-derived cells. Am J Pathol. 2004;164: 1935–1947. Pmid:15161630
  22. Laschke MW, Harder Y, Amon M, Martin I, Farhadi J, Ring A, et al. Angiogenesis in tissue engineering: breathing life into constructed tissue substitutes. Tissue Engineering. 2006;12: 2093–2104. pmid:16968151.
  23. Romano Di Peppe S, Mangoni A, Zambruno G, Spinetti G, Melillo G, Napolitano M, et al. Adenovirus-mediated VEGF (165) gene transfer enhances wound healing by promoting angiogenesis in CD1 diabetic mice. Gene Therapy. 2002;9: 1271–1277. pmid:12224009
  24. Syeda MM, Jing X, Mirza RH, Yu H, Sellers RS, Chi Y. Prostaglandin transporter modulates wound healing in diabetes by regulating prostaglandin-induced angiogenesis. Am J Pathol. 2012;181: 334–346. Pmid:22609345
  25. Bai H, McGaig CD, Forrester JV, et al. DC electric fields induce distinct preangiogenic responses in microvascular and macrovascular cells. Arterioscler Thromb Vasc Biol. 2004 Jul;24(7):1234-9.
  26. Hang J, Kong L, Gu JW, Adair TH. VEGF gene expression is upregulated in electrically stimulated rat skeletal muscle. Am J Physiol. 1995;269: H1827–1831. Pmid:7503283
  27. Kanno S, Oda N, Abe M, Saito S, Hori K, Handa Y, et al. Establishment of a simple and practical procedure applicable to therapeutic angiogenesis. Circulation. 1999;99: 2682–2687. Pmid:10338463
  28. Sebastian, A., Syed, F., Perry, D., Balamurugan, V., Colthurst, J., Chaudhry, I.H. and Bayat, A. (2011), Degenerate waves accelerate wound healing. Wound Repair Regen, 19: 693-708. 
  29. Arnold F, West DC. Angiogenesis in wound healing. Pharmacol Ther. 1991;52: 407–422. Pmid:1726477
  30. Hunckler J, de Mel A. A current affair: electrotherapy in wound healing. Multidiscip Healthc. 2017 Apr 20;10:179-194. doi: 10.2147/JMDH.S127207.
  31. Junger M, Arnold A, Zuder D, Stahl HW, Heising S. Local therapy and treatment costs of chronic, venous leg ulcers with electrical stimulation (Dermapulse): a prospective, placebo controlled, double blind trial. Wound Repair Regen. 2008;16: 480–487. Pmid:18638265
  32. Petrofsky J, Lawson D, Prowse M, Suh HJ. Effects of a 2-, 3- and 4-electrode stimulator design on current dispersion on the surface and into the limb during electrical stimulation in controls and patients with wounds. J Med Eng Technol. 2008;32: 485–497. pmid:19005963
  33. Suh H, Petrofsky J, Fish A, Hernandez V, Mendoza E, Collins K, et al. A new electrode design to improve outcomes in the treatment of chronic non-healing wounds in diabetes. Diabetes Technol Ther. 2009;11: 315–322. Pmid:19425879
  34. Ashrafi, MH, Alonso Rasgado, T, Baguneid, M & Bayat, A 2016, 'The efficacy of electrical stimulation in experimentally induced cutaneous wounds in animals', Veterinary Dermatology, vol. 27, no. 4, pp. 235-e57. 
  35. Bai H., Forrester, J V. DC electric stimulation upregulates angio-genic factors in endothelial cells through activation of VEGF receptors. Cytokine. 2011;55(1):110–115.
  36. Jerome Hunckler., Achala de Mel. A current affair: electrotherapy in wound healing. Journal of Multidisciplinary Healthcare 2017:10 179–19
  37. Kloth LC. Electrical stimulation for wound healing: a review of evidence from in vitro studies, animal experiments, and clinical trials. Int J Low Extrem Wounds. 2005;4(1):23–44.