Hypochlorous Acid: An Ideal Wound Care Agent With Powerful Microbicidal, Antibiofilm, and Wound Healing Potency

Serhan Sakarya, MD; Necati Gunay, MS; Meltem Karakulak, MS; Barcin Ozturk, MD; Bulent Ertugrul, MD

Disclosures

Wounds. 2014;26(12):342-350. 

In This Article

Discussion

Chronic wounds increase morbidity and mortality of patients and cause a significant burden to health care systems. Most chronic lesions are related to diabetes mellitus, venous stasis, peripheral vascular disease, and pressure ulcerations. Two critical factors important in wound healing are infection and cellular interaction. Infection is a major problem in wound healing, and chronic wounds can become contaminated by surrounding skin, local environment, and endogenous sources. Theoretically, chronic wounds offer ideal conditions for biofilm production. Biofilm is a primary impediment to the healing of chronic wounds[23] as it forms a physical barrier to bacteria from an external environment; provides a means for bacteria to communicate with each other, leading to an increase in virulence and antibiotic resistance; and provides an escape for bacteria from immune recognition.[24] In the current study, the authors demonstrated stabilized HOCl solution had powerful (Table 1) and rapid (Figure 1) killing effects on common etiologic microorganisms and had antibiofilm and microbicidal effects within biofilm (Figure 2). Although it has been shown that many antiseptic solutions have microbicidal activities against various microorganisms, their activities varied between the type of microorganisms (eg, gram negative, gram positive, or yeasts).[25–28] Previous studies have estimated that 106] neutrophils stimulated in vitro can produce 0.1μM HOCl and that this amount of HOCl can kill 1.5×107E. coli in less than 5 minutes.[17] Recently, Wang et al[27] demonstrated that stabilized HOCl had antimicrobial activity against S. aureus, P.aeruginosa, and C. albicans at concentrations ranging from 0.1 to 2.8 μg/mL and its TK values for these organisms was less than 1 minute.[28] These data correlated with the current study data but TK in this study was 0 minutes for all microorganisms.

Many antiseptic agents have more potent antibiofilm effects than antibiotics.[29–31] But the correlation between antibiofilm effect and microbicidal effect within biofilm has not been well described. In this study, the HOCl concentration for antibiofilm and microbicidal effects within biofilm was the same for each microorganism (Figure 2).

Although the biofilm eradication concentrations varied for each microorganisms, this was not correlated with the amount of biofilm. Since organic materials inactivate the stabilized HOCl solution activity, the difference in biofilm eradication concentration may be due to the diversity of biofilm structures of microorganisms.

Wound healing is a continuous sequence of 3 overlapping phases—inflammatory, proliferative, and maturation. At the inflammatory stage of injury, leukocytes have a critical role in the progress of the normal healing process.[32,33] Granulation tissue formation in the wound initiates with the proliferative phase and consists of cellular elements such as fibroblasts, keratinocytes, and inflammatory cells. Fibroblasts, derived from local mesenchymal cells, are the primary synthetic cells in the repair process of most structural proteins used during tissue reconstruction.[33] Although fibroblasts have a critical role in wound healing, its proliferation highly relates to keratinocyte proliferation and mediators secreted from keratinocytes and fibroblasts. Proinflammatory mediators, such as keratinocyte-derived IL-1 and inflammatory cell-derived IL-1, dominate keratinocyte-fibroblast interactions. Factors, such as keratinocyte growth factor, IL-6, endothelin-1 (ET-1), heparin-binding epidermal growth factor, and granulocte-monocyte colony stimulating factor, are upregulated in fibroblasts in response to IL-1. These factors stimulate keratinocyte proliferation and differentiation. Basement membrane constituents are also expressed by both keratinocytes and fibroblasts.[34] The defects on this mechanism or the proliferation of these cells impairs healing and causes chronic wounds.

Topical antiseptics in chronic wounds remain in widespread use today. These antiseptics are successful in microbial eradication, but at typical concentrations, they are cytotoxic and impair wound healing.[25–27] To demonstrate the effect of a stabilized HOCl solution on wound healing, the authors compared the migration of a wounded monolayer with povidone iodine and media alone in a cell culture model. The povidone iodine treatment disrupted fibroblast migration and detached cells after 4 hours. Stabilized HOCl solution decreased fibroblast migration with high doses, but it increased with a low dose when compared to the media control (Figures 3 and 4). Stabilized HOCl solution-treated keratinocyte cells and migration increased after 8 hours of treatment with the dose-dependent manner compared to the media control. In contrast, povidone iodine decreased migration at all dilutions after 4 hours of treatment (Figures 5 and 6). Moreover, short term treatment had the same effects on fibroblasts and keratinocyte migration.

Recent in vitro and clinical studies with super-oxidized solutions (SOS), supported these findings. In vitro studies with fibroblasts have shown that SOS is significantly less cytotoxic than hydrogen peroxide and does not induce genotoxicity or accelerated aging.[35] In clinical studies with chronic diabetic foot ulcers, osteomyelitis, and pressure ulcer treatment, HOCl has been impeded by infectious complications without application of systematic antibiotic therapy and a shortened healing period without any local side effects such as allergy or dermal irritation.[36,37]

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