Ozone, Wounds and Healing
(Complete Version)
The increase in ageing and diabetes, together with inadequate health programmes, highlight the problem of having to deal with more than 1.5 billion people affected by infectious diseases of the skin and mucous membranes, due to bacteria, viruses, protozoa and metabolic disorders. The clinical observation of diseases such as diabetic foot, bedsores, trauma ulcers or burns, chronic viral infections due to herpes I and II, human papilloma and vaginal infections due to Candida, Trichomonas or Chlamidia, infections of the anal mucosa such as scabs and fistular abscesses, as well as aphthous ulcers in the mouth.
These infections are rarely fatal, but they cause considerable concern (and chronicity), especially in diabetic and/or cardiovascular patients, HIV-positive people and addicts, often with tissue hypoxia.
Usually, this condition leads to expensive and not very effective medication, since an infection in hypoxic tissue presents methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa, which causes the patient to become frustrated by the lack of treatment results – verified by the failure of the tissue to heal[i] – and consequently to default on treatment.
Healing is a multi-stage process involving blood coagulation, inflammation, tissue proliferation and remodelling[ii] but if the immune system is weak, as is commonly seen in chronic infections, it’s unlikely to work properly, and even the use of growth factors won’t help in heavily infected chronic ulcers. The fact is that healing is a critical process for the skin and is known to be affected by oxidative stress as well as decreasing with ageing[iii].
Even so, although the exact healing process is complex, it is known that it begins with the transformation of keratocytes into cells capable of replicating and migrating, expressing various molecules that promote invasion of the damaged epithelial matrix and consequent re-epithelialisation of the wound surface[iv].
Ozonated Oils
When blood is ozonated, it reacts with soluble antioxidants and polyunsaturated fatty acids, oxidising them[v]. As a result of the reaction with ozone, these PUFA, which are characterised by the presence of double bonds, are oxidised and linked to an oxygen atom. From this observation, ozonised oils were born, which are used for various pathologies such as joints and especially dermatology[vi].
The use of ozone oils seems promising, especially in the healing process of wounds/skin diseases, primarily because it eliminates pathogens, but also because it is capable of releasing oxygen, activating fibroblast proliferation and thus promoting the reconstruction of the intercellular matrix, promoting keratinoblast proliferation and healing.
How ozonated oils actually work remains theoretical, but it is postulated that when the stable triozonide comes into contact with the exudate (which is hot), it decomposes into different peroxides which quickly dissolve, generating hydrogen peroxides, which explains its disinfectant and stimulant activity. Exposure to ozone is also associated with the activation of transcription factor beta (TGF-β), which is a critical factor in tissue remodelling[vii].
Topical treatment with ozone already has several successful studies and meta-analyses in herpes zoster[viii], psoriasis[ix]second-degree burns (with better results than hyaluronic acid[x]), varicose leg ulcers[xi], periodontitis[xii], interdigital erythrasma[xiii], among others.
[i] Chronic wound care. Lancet. 2008 Nov 29;372(9653):1860-1862. doi: 10.1016/S0140-6736(08)61793-6.
[ii] Wound healing – aiming for perfect skin regeneration. Science. 1997 Apr 4;276(5309):75-81.
[iii] Delayed wound healing in aged rats is associated with increased collagen gel remodeling and contraction by skin fibroblasts, not with differences in apoptotic or myofibroblast cell populations. Wound Repair Regen. 2001 May-Jun;9(3):223-37.
Age-associated changes in human epidermal cell renewal. J Gerontol. 1983 Mar;38(2):137-42.
[iv] Regulation of wound healing by growth factors and cytokines. Physiol Rev. 2003 Jul;83(3):835-70.
[v] Chemical kinetics measurements on the reaction between blood and ozone. Int J Biol Macromol. 2005 Jul;36(1-2):61-5.
[vi] Therapeutic effects of topical application of ozone on acute cutaneous wound healing. J Korean Med Sci. 2009 Jun;24(3):368-74. doi: 10.3346/jkms.2009.24.3.368.
[vii] The role of connective tissue growth factor, a multifunctional matricellular protein, in fibroblast biology. Biochem Cell Biol. 2003 Dec;81(6):355-63.
[viii] Topical ozone therapy: An innovative solution to patients with herpes zoster. Zhong Nan Da Xue Xue Bao Yi Xue Ban. 2018 Feb 28;43(2):168-172. doi: 10.11817/j.issn.1672-7347.2018.02.011.
[ix] Clinical efficacy of ozonated oil in the treatment of psoriasis vulgaris. Zhong Nan Da Xue Xue Bao Yi Xue Ban. 2018 Feb 28;43(2):173-178. doi: 10.11817/j.issn.1672-7347.2018.02.012.
[x] Topical ozonated oil versus hyaluronic gel for the treatment of partial- to full-thickness second-degree burns: A prospective, comparative, single-blind, non-randomised, controlled clinical trial. Burns. 2013 Sep;39(6):1178-83. doi: 10.1016/j.burns.2013.03.002.
[xi] Randomized, controlled study of innovative spray formulation containing ozonated oil and α-bisabolol in the topical treatment of chronic venous leg ulcers. Adv Skin Wound Care. 2015 Sep;28(9):406-9. doi: 10.1097/01.ASW.0000470155.29821.ed.
[xii] The use of ozonated sea buckthorn oil in the prevention and treatment of tobacco dependence periodontitis in the experiment. Lik Sprava. 2014 Dec;(12):91-4.
[xiii] Treatment of interdigital foot Erythrasma with ozonated olive oil. Rev Med Inst Mex Seguro Soc. 2016 Jul-Aug;54(4):458-61.
