Cold atmospheric plasma improves cutaneous microcirculation in standardized acute wounds: Results of a controlled, prospective cohort study

Background: Given the high prevalence of wounds and their challenging treatment, the research of therapies to improve wound healing is of great clinical interest. In addition, the general consequences of developing chronic wounds constitute a large health economic aspect, which underscores the interest in the development of efficient treatment strategies. Direct cold atmospheric plasma (di_CAP) has been shown to have beneficial effects on microcirculation of human tissue (Kisch et al., 2016a). It also affects microbial settlements, which may have supportive effects on wound healing processes (Balzer et al., 2015). To treat these adequately, in our view, the positive effects on wound healing should be objectified by application on standardized wounds. However, wound healing is a complex process, depending on nutrient and oxygen supply by cutaneous blood circulation. In spite of microcirculation has been shown to improve in healthy skin by CAP, a quantification of the effect in a standardized wound model has never been evaluated (Kisch et al., 2016a). Based on this, we hypothesize that CAP also influences the microcirculation in standardized acute wounds in a prospective cohort study. Methods: Microcirculatory data of 20 healthy subjects (14 males, 6 females; mean age 40.85 ± 15.84 years; BMI 26.83 ± 7.27 kg/m2) were recorded continuously at a standardized acute wound after skin transplantation (donor site) at the thigh. Under standardized conditions, microcirculatory measurements were performed using a combined laser Doppler and photospectrometry system. After baseline measurement, CAP was applied by a dielectric barrier discharge (DBD) plasma device for 90 s to the acute wound area. Immediately after the application, cutaneous microcirculation was assessed for 30 min (min) at the same site. Results: After CAP application, tissue oxygen saturation immediately increased by 5% (92,66 ± 4,76% vs. Baseline 88,21 ± 6,52%, p < 0,01) in the first 60 s and remained significantly elevated for 4 min. Capillary blood flow increased by 19.3% within the first minute of CAP therapy (220.14 ± 65.91 AU vs. Baseline 184.52 ± 56.77 AU, p < 0.001). The statistically highly significant increase in blood flow continued over the entire measurement time. A maximum value was shown in the blood flow in the 15th minute (232.15 ± 58.90 AU, p < 0.001) according to CAP application. With regard to the output measurement, it represents a percentage increase of 25.8%. The measurement of post-capillary venous filling pressure at a tissue depth of 6-8 mm was 59.39 ± AU 12.94 at baseline measurement. After application, there were no significant changes. Conclusion: CAP increases cutaneous tissue oxygen saturation and capillary blood flow at the standardized acute wound healing model. These results support recently published data on wound healing after CAP treatment. However, further studies are needed to determine if this treatment can improve the reduced microcirculation in chronic wounds. Moreover, repetitive application protocols have to be compared with a single session treatment approach.