The £5billion Wound Care Problem

The burden of chronic wounds such as diabetic foot ulcers, leg ulcers and pressure ulcers on the NHS and health service providers globally is reaching epidemic proportions. It has been estimated that in 2012/13, 2.2 million wounds were managed by the NHS, with an associated annual cost of between £4.5 and £5.1 billion. Of these wounds, 731,000 leg ulcers carried a cost of almost £2 billion. In 2004, $12 billion were spent on the treatment of chronic wounds in the US. Worldwide, the prevalence of diabetic foot ulcers has recently been estimated to be 6.3% [1–3].

Patients living with a chronic wound suffer with pain, odour, social isolation, low self-esteem and depression, and an infected wound can lead in severe cases to death by septicaemia, with amputation then presenting the only viable option for survival. Current treatments fail to satisfactorily improve wound healing outcomes. The requirement to frequently redress wounds, in order to manage exudate and inspect the progression of healing, is a source of considerable discomfort for patients, a significant burden on healthcare staff and an encouragement to infection [4]. With an ageing population and antimicrobial resistance poised to further aggravate the problem, efforts must be made now to improve the prevention, early diagnosis and treatment of chronic wounds.

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Annual NHS Spend in Billions
Data based on review of published data; data and references available on file.
NHS data not adjusted for co-morbidities. Data correct as of March 2016.


Fourth State Technology and
Application to Wound Care.

Fourth State’s mission is to deliver on the promise of plasma medicine, for the NHS and around the world, with its patented Dual Plasma technology (GB2532195, WO/2016/071680). In combining thermal and non-thermal plasmas, which can be generated independently or simultaneously within a single device, Dual Plasma represents a highly flexible platform technology that can be tailored to an extensive range of treatments. Our Dual Plasma can also be packaged into many form factors, allowing seamless integration into existing clinical practices. For the cosmetic reduction of fine lines and wrinkles, we have packaged Dual Plasma into an ergonomic handpiece to create Nebulaskin (pictured opposite) allowing the aesthetic practitioner a high degree of position control in the application of thermal plasma. In a pilot study, the same device, producing a non-thermal plasma, has indicated a potential use in eradication of MRSA and Pseudomonas Aeruginosa. The results of a 60 second exposure are shown below.

In recent years, atmospheric pressure plasmas (ionized gas), both thermal (hot) and non-thermal (cold) varieties, have found novel applications in medicine. These include sterilisation, assisted coagulation, acceleration of wound healing and even treatment of certain cancers. Depending on the type of plasma and treatment application, the biological effects of plasma can be attributed to the synergistic effects of heat, ultra-violet radiation, electric fields and Reactive Oxygen and Nitrogen Species (RONS) produced by the plasma such as nitric oxide (NO), hydrogen peroxide (H2O2), and ozone (O3) [5–7]. Many in-vitro, in-vivo and clinical studies have now demonstrated the utility of both thermal [8–10] and non-thermal [11-13] plasmas in sterilisation and acceleration of wound healing, promising a paradigm shift in the treatment of chronic wounds and management of antimicrobial resistance.


 
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Fourth State has partnered with Queen Mary University through the Medcity“Collaborate to Innovate” (C2N) program. This year long study will be conducted at the Blizard institute by Dr. Rosalind Hannen and aims to take on three challenges. The application was the highest rated of those submitted. 
 

  • Challenge 1: High-throughput in vitro wound healing models for plasma output optimisation
  • Challenge 2: Can 4SM Plasma Technology Improve Diabetic Wound Healing?
  • Challenge 3: Optimisation of Plasma Platforms- Open versus Enclosed Plasma Source
     

Success in this project would be convincing pre-clinical in vitro and in vivo data demonstrating Fourth States plasma technology actively promotes healthy wound healing and prevents skin infection by sterilisation. The pre-clinical data will be applied to create an optimised plasma tool with a novel biomedical dressing ready for human clinical trials and ultimately CE approval for wound healing. 

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Fourth State has successfully secured a 3 year PhD position funded by the British Skin Foundation and in collaboration in with the university of Hull. The academic lead for the project Dr. Matthew Hardman, has over 25 years of experience investigating wound repair mechanisms and specialises in the role hormones and aging play in wound healing. This project has two main aims:

  • Aim 1: To Profile the bacteria in both existing wound tissue and newly collected clinical samples, linking specific microbial species to changes in the host response. 
  • Aim 2: To test the efficacy, selectivity and mode of action of a Fourth States hand-held Dual Plasma device for the promotion of healing.

Dr Hardman has been working with Fourth State since our founding to provide pilot data which demonstrated the use of our Dual Plasma technology to stop the spread of MSSA and Pseudomonas Aeruginosa.

 
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References: 

[1] J. F. Guest, N. Ayoub, “Health economic burden that different wound types impose on the UK’s National Health Service,” International wound journal, vol. 14, no. 2, pp. 322–330, 2017.

[2] S. Schreml and M. Berneburg, “The global burden of diabetic wounds,” British Journal of Dermatology, vol. 176, no. 4, pp. 845–846, 2017.

[3] P. Zhang, J. Lu,  “Global epidemiology of diabetic foot ulceration: a systematic review and meta-analysis,” Annals of Medicine, vol. 49, no. 2, pp.106–116, 2017.

[4] S. Vuorisalo, M. Venermo, “Treatment of diabetic foot ulcers,” J Cardiovasc Surg, vol. 50, pp. 275–91, 2009.

[5]   A. Fridman and G. Friedman, Plasma medicine. John Wiley & Sons, 2012.

[6]   G. Lloyd, G. Friedman “Gas plasma: medical uses and developments in wound care,” Plasma Processes and Polymers, vol. 7, no. 3–4, pp. 194–211, 2010.

[7]   T. Von Woedtke, S. Reuter “Plasmas for medicine,” Physics Reports, vol. 530, no. 4, pp. 291–320, 2013.

[8]   M. A. Malik, “Nitric oxide production by high voltage electrical discharges for medical uses: a review,” Plasma Chemistry and Plasma Processing, vol. 36, no. 3, pp. 737–766, 2016.

[9]   A. V. Pekshev, A. B. Shekhter “Study of plasma-chemical NO-containing gas flow for treatment of wounds and inflammatory processes,” Nitric Oxide, 2017.

 [10]  A. B. Shekhter, V. A. Serezhenkov “Beneficial effect of gaseous nitric oxide on the healing of skin wounds,” Nitric oxide, vol. 12, no. 4, pp. 210–219, 2005.

 [11]  B. Haertel, T. von Woedtke “Non-thermal atmospheric-pressure plasma possible application in wound healing,” Biomolecules & therapeutics, vol. 22, no. 6, p. 477, 2014.

[12]   G. Isbary, J. Zimmermann, “Non-thermal plasma—More than five years of clinical experience,” Clinical Plasma Medicine, vol. 1, no. 1, pp. 19–23, 2013.

 [13]  N. M. Nasir, B. Lee, S. Yap “Cold plasma inactivation of chronic wound bacteria,” Archives of biochemistry and biophysics, vol. 605, pp. 76–85, 2016.