Gas plasma-oxidized sodium chloride acts via hydrogen peroxide in a model of peritoneal carcinomatosis.

Gas plasma technology generates reactive oxygen and nitrogen species (ROS/RNS), inducing lethal oxidative damage in tumor cells. The transfer of gas plasma-derived ROS/RNS into liquids has been proposed as an innovative anti-cancer strategy targeting peritoneal carcinomatosis (PC). However, the mechanism of action is under debate. To this end, we compared gas plasma-oxidized medical-grade sodium chloride (oxNaCl) with a concentration-matched control (cmc) of NaCl enriched with equivalent concentrations of H2O2 and NO3- in several cell lines and models of PC. Strikingly, oxNaCl and cmc performed equally well in oxidation and cytotoxic activity in tumor cells in two-dimensional cultures, three-dimensional (3D) tumor spheroids, vascularized 3D tumors grown on chicken-embryo chorioallantoic membranes, and a syngeneic PC mouse model in vivo. Given the importance of immunotherapies in oncology today, we focused on immunological consequences of the treatment. Again, to a similar extent, oxNaCl and cmc increased tumor cell immunogenicity and enhanced uptake by and maturation of peripheral blood monocyte-derived dendritic cells together with an inflammatory secretion profile. Furthermore, NanoString gene expression profiling revealed immune system processes and unfolded protein response-related pathways as being linked to the observed anti-tumor effects for both oxNaCl and cmc. In conclusion, gas plasma-generated oxNaCl and cmc showed equal therapeutic efficacy in our PC-related models. In light of the many promising anti-cancer studies of gas plasma-oxidized liquids and the convenient production of corresponding cmcs in large quantities as needed in clinics, our findings may spur research lines based on low-dose oxidants in peritoneal cancer therapy.

Proteomic profiling of antibiotic-resistant Escherichia coli GW-AmxH19 isolated from hospital wastewater treated with physical plasma.

Microorganisms which are resistant to antibiotics are a global threat to the health of humans and animals. Wastewater treatment plants are known hotspots for the dissemination of antibiotic resistances. Therefore, novel methods for the inactivation of pathogens, and in particular antibiotic-resistant microorganisms (ARM), are of increasing interest. An especially promising method could be a water treatment by physical plasma which provides charged particles, electric fields, UV-radiation, and reactive species. The latter are foremost responsible for the antimicrobial properties of plasma. Thus, with plasma it might be possible to reduce the amount of ARM and to establish this technology as additional treatment stage for wastewater remediation. However, the impact of plasma on microorganisms beyond a mere inactivation was analyzed in more detail by a proteomic approach. Therefore, Escherichia coli GW-AmxH19, isolated from hospital wastewater in Germany, was used. The bacterial solution was treated by a plasma discharge ignited between each of four pins and the liquid surface. The growth of E. coli and the pH-value decreased during plasma treatment in comparison with the untreated control. Proteome and antibiotic resistance profile were analyzed. Concentrations of nitrite and nitrate were determined as long-lived indicative products of a transient chemistry associated with reactive nitrogen species (RNS). Conversely, hydrogen peroxide served as indicator for reactive oxygen species (ROS). Proteome analyses revealed an oxidative stress response as a result of plasma-generated RNS and ROS as well as a pH-balancing reaction as key responses to plasma treatment. Both, the generation of reactive species and a decreased pH-value is characteristic for plasma-treated solutions. The plasma-mediated changes of the proteome are discussed also in comparison with the Gram-positive bacterium Bacillus subtilis. Furthermore, no effect of the plasma treatment, on the antibiotic resistance of E. coli, was determined under the chosen conditions. The knowledge about the physiological changes of ARM in response to plasma is of fundamental interest to understand the molecular basis for the inactivation. This will be important for the further development and implementation of plasma in wastewater remediation.

Cold atmospheric plasma-activated medium for potential ovarian cancer therapy.

Cold atmospheric plasma (CAP) has emerged as an innovative tool with broad medical applications, including ovarian cancer (OC) treatment. By bringing CAP in close proximity to liquids such as water or cell culture media, solutions containing reactive oxygen species (ROS) and reactive nitrogen species (RNS) are generated, called plasma-activated media (PAM). In this systematic review, we conduct an in-depth analysis of studies focusing on PAM interactions with biological substrates. We elucidate the diverse mechanisms involved in the activation of different media and the complex network of chemical reactions underlying the generation and consumption of the prominent reactive species. Furthermore, we highlight the promises of PAM in advancing biomedical applications, such as its stability for extended periods under appropriate storage conditions. We also examine the application of PAM as an anti-cancer and anti-metastatic treatment for OC, with a particular emphasis on its ability to induce apoptosis via distinct signaling pathways, inhibit cell growth, suppress cell motility, and enhance the therapeutic effects of chemotherapy. Finally, the future outlook of PAM therapy in biomedical applications is speculated, with emphasis on the safety issues relevant to clinical translation.

Exploring the Influence of Cold Plasma on Epidermal Melanogenesis In Situ and In Vitro.

Epidermal melanin synthesis determines an individual's skin color. In humans, melanin is formed by melanocytes within the epidermis. The process of melanin synthesis strongly depends on a range of cellular factors, including the fine-tuned interplay with reactive oxygen species (ROS). In this context, a role of cold atmospheric plasma (CAP) on melanin synthesis was proposed due to its tunable ROS generation. Herein, the argon-driven plasma jet kINPen® MED was employed, and its impact on melanin synthesis was evaluated by comparison with known stimulants such as the phosphodiesterase inhibitor IBMX and UV radiation. Different available model systems were employed, and the melanin content of both cultured human melanocytes (in vitro) and full-thickness human skin biopsies (in situ) were analyzed. A histochemical method detected melanin in skin tissue. Cellular melanin was measured by NIR autofluorescence using flow cytometry, and a highly sensitive HPLC-MS method was applied, which enabled the differentiation of eu- and pheomelanin by their degradation products. The melanin content in full-thickness human skin biopsies increased after repeated CAP exposure, while there were only minor effects in cultured melanocytes compared to UV radiation and IBMX treatment. Based on these findings, CAP does not appear to be a useful option for treating skin pigmentation disorders. On the other hand, the risk of hyperpigmentation as an adverse effect of CAP application for wound healing or other dermatological diseases seems to be neglectable.

Recent advances in cold atmospheric plasma (CAP) for breast cancer therapy.

The serious problems of conventional breast cancer therapy strategies such as drug resistance, severe side effects, and lack of selectivity prompted the development of various cold atmospheric plasma (CAP) devices. Due to its advanced technology, CAP can produce a unique environment rich in reactive oxygen and nitrogen species (RONS), photons, charged ions, and an electric field, making it a promising revolutionary platform for cancer therapy. Despite substantial technological successes, CAP-based therapeutic systems are encounter with distinct limitations, including low control of the generated RONS, poor knowledge about its anticancer mechanisms, and challenges concerning designing, manufacturing, clinical translation, and commercialization, which must be resolved. The latest developments in CAP-based therapeutic systems for breast cancer treatment are discussed in this review. More significantly, the integration of CAP-based medicine approaches with other breast cancer therapies, including chemo- and nanotherapy is thoroughly addressed.

A Prospective Randomized Controlled Pilot Study to Assess the Response and Tolerability of Cold Atmospheric Plasma for Rosacea.

INTRODUCTION: Rosacea is a common, facial, chronic inflammatory skin disease. Due to its complex pathogenesis, adequate therapy of rosacea can be challenging. An innovative recent therapeutic tool is cold atmospheric plasma (CAP), which is already established in the treatment of chronic wounds and promising in different other skin diseases. METHODS: In a split-face pilot study we investigated dielectric-barrier-discharged CAP in erythemato-telangiectatic (ETR) and/or papulopustular rosacea (PPR). CAP treatment was applied on lesional skin of a randomized side once daily (90 s/area) for 6 weeks. The other untreated side served as control. Co-primary endpoints were ≥1 improvement of the Investigator Global Assessment (IGA) score on the treated side compared to control and a decline of the Dermatology Life Quality Index (DLQI) after 6 weeks. Secondary endpoints included inflammatory lesion count (papules and pustules), skin redness intensity and erythema size. Adverse events (AEs) were recorded constantly. Additionally, participants were weekly assessed for symptoms, skin condition, trigger factors, skin care, treatment success, and local tolerance parameters. All p values were calculated using the Wilcoxon signed-rank test. RESULTS: Twelve subjects (ETR, n = 3; ETR and PPR, n = 9) completed the study. DLQI was significantly improved after 6 weeks (p = 0.007). On the CAP-treated side, lesions (p = 0.007) and erythema size (p = 0.041) were significantly reduced compared to the control. IGA (p = 0.2) and skin redness intensity (p = 0.5) did not differ significantly between control and CAP-treated side. No serious AEs occurred and treatment was well tolerated. CONCLUSION: CAP is a promising new treatment of rosacea, especially for PPR.

Split-face comparison of hydroquinone 4% plus nitrogen plasma vs. hydroquinone 4% alone in the treatment of melasma.

Treatment of skin diseases is important yet challenging. One of the most common skin diseases in women is melasma, which features acquired facial hyperpigmentation. We studied the effect of cold atmospheric nitrogen plasma on this disease. To characterize the nitrogen plasma, we obtained the relative intensity of the species and the plasma temperature and skin temperature during processing at different input powers and gas flows. Patients complaining of melasma were treated with hydroquinone on both sides of the face, and one side was randomly selected for additional nitrogen plasma therapy. Eight treatment sessions of plasma processing were provided 1 week apart, and one follow-up session was scheduled 1 month after the end of treatment. The rate of improvement was scored by a dermatologist in the eighth session and 1 month following the last session using the modified Melasma Area Severity Index (mMASI). Skin biomechanical characteristics such as melanin, cutaneous resonance running time (CRRT), transepidermal water loss (TEWL), and hydration were measured at baseline and during the fourth, eighth, and follow-up sessions. On both sides, we observed a significant decrease in both CRRT and melanin (P < 0.05). TEWL did not change on both sides, while hydration decreased significantly only on the side to which hydroquinone was applied in isolation (P < 0.05). According to clinical scores, on both sides, we had significant improvement. On the side that plasma was not applied, the percentage reduction of pigmentation (mMASI) in the eighth and follow-up sessions in comparison with the baseline was 5.49 ± 8.50% and 33.04 ± 9.17%, respectively, while on the other side, these figures were 20.57 ± 6.64% and 48.11 ± 11%. For melanin, these figures were 13.84 ± 4.84% and 18.23 ± 7.10% on the hydroquinone side and 21.56 ± 3.13% and 23.93 ± 3.02% on the other side. According to these results, nitrogen plasma can safely complement topical hydroquinone to improve clinical outcomes when treating melasma without causing stratum corneum damage or skin discomfort, though confirmatory studies are needed.

Positive effects of cold atmospheric plasma on pH in wounds: a pilot study.

OBJECTIVE: Cold atmospheric plasma (CAP) is a promising new option for the treatment of hard-to-heal (chronic) wounds. The aim of this study was to observe the effect of CAP on wound pH, as a correlation between the pH of a wound and its healing tendency has been established in the literature. METHOD: Patients with hard-to-heal wounds were treated with CAP in addition to standard treatment. Treatment was performed with the aid of a small, mobile plasma device, which was used for one minute at a time during dressing changes. The pH value, wound size, and other parameters, such as exudate and signs of infection, were recorded for each treatment. RESULTS: A total of 10 patients took part in the study. During the observation period, there was a significant reduction in pH from a markedly alkaline pH of 9.6 to a neutral pH of 7. This was accompanied by a marked reduction in wound size by an average of 76% with seven applications of CAP within 28 days. The evaluation of tissue granulation, exudate and signs of infection showed a positive trend. CONCLUSION: The number of patients in the present study is not sufficient to prove the relationship between the pH value of the wound and the treatment with CAP. However, there are clear indications that the positive effects of CAP on wound healing, which are recognised in several publications, are also due to its influence on wound pH value.

Low-Temperature Plasma Techniques in Biomedical Applications and Therapeutics: An Overview.

Plasma, the fourth fundamental state of matter, comprises charged species and electrons, and it is a fascinating medium that is spread over the entire visible universe. In addition to that, plasma can be generated artificially under appropriate laboratory techniques. Artificially generated thermal or hot plasma has applications in heavy and electronic industries; however, the non-thermal (cold atmospheric or low temperature) plasma finds its applications mainly in biomedicals and therapeutics. One of the important characteristics of LTP is that the constituent particles in the plasma stream can often maintain an overall temperature of nearly room temperature, even though the thermal parameters of the free electrons go up to 1 to 10 keV. The presence of reactive chemical species at ambient temperature and atmospheric pressure makes LTP a bio-tolerant tool in biomedical applications with many advantages over conventional techniques. This review presents some of the important biomedical applications of cold-atmospheric plasma (CAP) or low-temperature plasma (LTP) in modern medicine, showcasing its effect in antimicrobial therapy, cancer treatment, drug/gene delivery, tissue engineering, implant modifications, interaction with biomolecules, etc., and overviews some present challenges in the field of plasma medicine.

Effect of Nanosecond Pulsed Currents on Directions of Cell Elongation and Migration through Time-Lapse Analysis.

It is generally known that cells elongate perpendicularly to an electric field and move in the direction of the field when an electric field is applied. We have shown that irradiation of plasma-simulated nanosecond pulsed currents elongates cells, but the direction of cell elongation and migration has not been elucidated. In this study, a new time-lapse observation device that can apply nanosecond pulsed currents to cells was constructed, and software to analyze cell migration was created to develop a device that can sequentially observe cell behavior. The results showed nanosecond pulsed currents elongate cells but do not affect the direction of elongation and migration. It was also found the behavior of cells changes depending on the conditions of the current application.

Cold atmospheric pressure plasma treatment combined with starvation increases autophagy and apoptosis in melanoma in vitro and in vivo.

Despite advances in therapy, malignant melanoma remains a fatal disease. Among several emerging approaches to combat cancer, cold atmospheric pressure plasma (CAP) has shown promising results as a novel antitumor agent in preclinical models so far. The technology mainly relies on the emittance of various reactive oxygen and nitrogen species (ROS/RNS) that are tumor-toxic at high concentrations. Moreover, malignant melanoma has a metabolic dimension that can be targeted by mild starvation. To this end, we investigated the combined effect of starvation and CAP treatment on melanoma in vitro and in vivo. In vitro, starvation+CAP led to cell morphology changes, decreased metabolic activity and increased lipid peroxidation accompanied by apoptosis and DNA fragmentation in murine B16 melanoma cells but not murine non-malignant L929 fibroblasts. This was paralleled by increased apoptosis (Bax, Bcl-2 and Caspase-3) and autophagy (Lc3 and Atg5)-related gene expression. In vivo, starvation reduced tumor burden. Combination with CAP treatment augmented this effect significantly, albeit there was no difference of combination treatment to CAP exposure alone. Interestingly, there was an overall greater increase of Lc3 and Atg5 in the tumor tissue compared to CAP exposure alone, while starvation-induced autophagy-related gene expression was similar to in the combination group. These data collectively suggest that CAP-derived ROS/RNS treatment and autophagy-induction augment antitumor effects in malignant melanoma in vitro and in vivo.

Multimodal treatment combining cold atmospheric plasma and acidic fibroblast growth factor for multi-tissue regeneration.

Cold atmospheric plasma (CAP) is an emerging technology for biomedical applications, exemplified by its antimicrobial and antineoplastic potentials. On the contrary, acidic fibroblast growth factor (aFGF) has been a long-standing potent mitogen for cells from various origins. In this study, we are the first to develop a multimodal treatment combining the aforementioned physicochemical and pharmacological treatments and investigated their individual and combined effects on wound healing, angiogenesis, neurogenesis, and osteogenesis. This work was performed at the tissue, cellular, protein, and gene levels, using histochemical staining, flow cytometry, ELISA, and PCR, respectively. Depending on the type of target tissue, various combinations of aforementioned methods were used. The results showed that the enhancement on would healing and angiogenesis by CAP and aFGF were synergistic. The former was manifested by increased murine fibroblast proliferation and reduced cutaneous tissue inflammation, whereas the latter by upregulated proangiogenic markers in vivo, for example, CD31, VEGF, and TGF-ß, and downregulated antiangiogenic proteins in vitro, for example, angiostatin and angiopoietin-2, respectively. In addition, aFGF outperformed CAP during neurogenesis, which was evidenced by superior neurite outgrowth, while CAP exceeded aFGF in osteogenesis which was demonstrated by more substantial bone nodule formation. These novel findings not only support the fact that CAP and aFGF are both multipotent agents during tissue regeneration, but also highlight the potential of our multimodal treatment combining the individual advantages of CAP and aFGF. The versatile administration route, that is, topical and/or systemic, might further broaden its applications.

Topically Confined Enhancement of Cutaneous Microcirculation by Cold Plasma.

INTRODUCTION: We aim to explore potentials and modalities of cold atmospheric pressure plasma (CAP) for the subsequent development of therapies targeting an increased perfusion of the lower leg skin tissue. In this study, we addressed the question whether the microcirculation enhancement is restricted to the tissue in direct contact with plasma or if adjacent tissue might also benefit. METHODS: A dielectric barrier discharge (DBD)-generated CAP device exhibiting an electrode area of 27.5 cm2 was used to treat the anterior lower leg of ten healthy subjects for 4.5 min. Subsequently, hyperspectral imaging was performed to measure the tempospatially resolved characteristics of microcirculation parameters in superficial (up to 1 mm) and deeper (up to 5 mm) skin layers. RESULTS: In the tissue area covered by the plasma electrode, DBD-CAP treatment enhances most of the perfusion parameters. The maximum oxygen saturation increase reached 8%, the near-infrared perfusion index (NIR) increased by a maximum of 4%, and the maximum tissue hemoglobin increase equaled 14%. Tissue water index (TWI) was lower in both the control and the plasma groups, thus not affected by the DBD-CAP treatment. Yet, our study reveals that adjacent tissue is hardly affected by the enhancements in the electrode area, and the effects are locally confined. CONCLUSION: Application of DBD-CAP to the lower leg resulted in enhancement of cutaneous microcirculation that extended 1 h beyond the treatment period with localization to the tissue area in direct contact with the cold plasma. This suggests the possibility of tailoring application schemes for topically confined enhancement of skin microcirculation, e.g., in the treatment of chronic wounds.

Development of a Mobile Sensory Device to Trace Treatment Conditions for Various Medical Plasma Source Devices.

The emerging use of low-temperature plasma in medicine, especially in wound treatment, calls for a better way of documenting the treatment parameters. This paper describes the development of a mobile sensory device (referred to as MSD) that can be used during the treatment to ease the documentation of important parameters in a streamlined process. These parameters include the patient's general information, plasma source device used in the treatment, plasma treatment time, ambient humidity and temperature. MSD was developed as a standalone Raspberry Pi-based version and attachable module version for laptops and tablets. Both versions feature a user-friendly GUI, temperature-humidity sensor, microphone, treatment report generation and export. For the logging of plasma treatment time, a sound-based plasma detection system was developed, initially for three medically certified plasma source devices: kINPen® MED, plasma care®, and PlasmaDerm® Flex. Experimental validation of the developed detection system shows accurate and reliable detection is achievable at 5 cm measurement distance in quiet and noisy environments for all devices. All in all, the developed tool is a first step to a more automated, integrated, and streamlined approach of plasma treatment documentation that can help prevent user variability.

Biocompatible Gas Plasma Treatment Affects Secretion Profiles but Not Osteogenic Differentiation in Patient-Derived Mesenchymal Stromal Cells.

Cold physical plasma (CPP), a partially ionized gas that simultaneously generates reactive oxygen and nitrogen species, is suggested to provide advantages in regenerative medicine. Intraoperative CPP therapy targeting pathologies related to diminished bone quality could be promising in orthopedic surgery. Assessment of a clinically approved plasma jet regarding cellular effects on primary bone marrow mesenchymal stromal cells (hBM-MSCs) from relevant arthroplasty patient cohorts is needed to establish CPP-based therapeutic approaches for bone regeneration. Thus, the aim of this study was to derive biocompatible doses of CPP and subsequent evaluation of human primary hBM-MSCs' osteogenic and immunomodulatory potential. Metabolic activity and cell proliferation were affected in a treatment-time-dependent manner. Morphometric high content imaging analyses revealed a decline in mitochondria and nuclei content and increased cytoskeletal compactness following CPP exposure. Employing a nontoxic exposure regime, investigation on osteogenic differentiation did not enhance osteogenic capacity of hBM-MSCs. Multiplex analysis of major hBM-MSC cytokines, chemokines and growth factors revealed an anti-inflammatory, promatrix-assembling and osteoclast-regulating secretion profile following CPP treatment and osteogenic stimulus. This study can be noted as the first in vitro study addressing the influence of CPP on hBM-MSCs from individual donors of an arthroplasty clientele.

Biological Risk Assessment of Three Dental Composite Materials following Gas Plasma Exposure.

Gas plasma is an approved technology that generates a plethora of reactive oxygen species, which are actively applied for chronic wound healing. Its particular antimicrobial action has spurred interest in other medical fields, such as periodontitis in dentistry. Recent work has indicated the possibility of performing gas plasma-mediated biofilm removal on teeth. Teeth frequently contain restoration materials for filling cavities, e.g., resin-based composites. However, it is unknown if such materials are altered upon gas plasma exposure. To this end, we generated a new in-house workflow for three commonly used resin-based composites following gas plasma treatment and incubated the material with human HaCaT keratinocytes in vitro. Cytotoxicity was investigated by metabolic activity analysis, flow cytometry, and quantitative high-content fluorescence imaging. The inflammatory consequences were assessed using quantitative analysis of 13 different chemokines and cytokines in the culture supernatants. Hydrogen peroxide served as the control condition. A modest but significant cytotoxic effect was observed in the metabolic activity and viability after plasma treatment for all three composites. This was only partially treatment time-dependent and the composites alone affected the cells to some extent, as evident by differential secretion profiles of VEGF, for example. Gas plasma composite modification markedly elevated the secretion of IL6, IL8, IL18, and CCL2, with the latter showing the highest correlation with treatment time (Pearson's r > 0.95). Cell culture media incubated with gas plasma-treated composite chips and added to cells thereafter could not replicate the effects, pointing to the potential that surface modifications elicited the findings. In conclusion, our data suggest that gas plasma treatment modifies composite material surfaces to a certain extent, leading to measurable but overall modest biological effects.

Cold atmospheric plasma as an interface biotechnology for enhancing surgical implants.

Cold atmospheric plasma (CAP) has been intensively researched for direct treatment of living cells and tissues. Significant attention is now being given to its indirect applications in plasma medicine. Surgical implant is an exemplary conveyor to deliver the therapeutic effects of plasma to patients. There is a constant drive to enhance the clinical performance of surgical implants, targeting at the implant-tissue interface. As a versatile and potent tool, CAP is capable of ameliorating surgical implants using various strategies of interface biotechnology, such as surface modification, coating deposition, and drug delivery. Understanding the chemical, physical, mechanical, electrical, and pharmacological processes occurring at the implant-tissue interface is crucial to effective application of CAP as an interface biotechnology. This preclinical review focuses on the recent advances in CAP-assisted implant-based therapy for major surgical specialties. The ultimate goal here is to elicit unique opportunities and challenges for translating implant science to plasma medicine.

The antimicrobial and tissue healing efficacy of the atmospheric pressure cold plasma on grade III infected pressure ulcer: randomized controlled in vivo experiment.

AIM: To evaluate the antimicrobial efficacy and wound healing effect of atmospheric pressure cold plasma (APCP) on an infected pressure ulcer (IPUs) model that was created on rats. METHODS: A total of 18 rats was divided into APCP, silver sulfadiazine (AgS) and control groups to have six rats in each group. A third-grade pressure ulcer model was developed on the back of each of the rats, and pressure ulcers were infected by inoculation of multidrug resistance (MDR) Pseudomonas aeruginosa. A portable dielectric barrier discharge device was used to generate cold air plasma. APCP, AgS and saline treatments were carried out once a day for 14 days. The effectiveness of the treatment was evaluated on days 5, 10 and 15. Surface area, depth, pressure ulcer healing scale (PUSH) and microbiological examination were used for evaluation. RESULTS: The results of this study showed that APCP was superior over AgS application and irrigation with saline by means of the reduction in surface area and depth of ulcers. Furthermore, PUSH score in plasma group was lower than other groups and histopathological examination showed a higher epithelization in APCP group. The average reductions of MDR P. aeruginosa for APCP, AgS and control groups were determined as 5·64 ± 1·87, 1·91 ± 0·90 and 1·22 ± 0·88 log10 CFU per gram tissue, respectively. CONCLUSION: Atmospheric pressure cold plasma healed IPUs better than AgS. SIGNIFICANCE AND IMPACT OF THE STUDY: Portable cold plasma devices could be a potential novel treatment modality for the patients who have IPUs.

The Response and Tolerability of a Novel Cold Atmospheric Plasma Wound Dressing for the Healing of Split Skin Graft Donor Sites: A Controlled Pilot Study.

INTRODUCTION: Cold atmospheric plasma (CAP) has positive effects on wound healing and antimicrobial properties. However, an ongoing challenge is the development of specific modes of application for different clinical indications. OBJECTIVES: We investigated in a prospective pilot study the response and tolerability of a newly developed CAP wound dressing for the acute healing of split skin graft donor sites compared to conventional therapy. METHODS: We applied both treatments to each patient (n = 10) for 7 days and measured 4 parameters of wound healing every other day (i.e., 1,440 measurements) using a hyperspectral imaging camera. Additionally, we evaluated the clinical appearance and pain levels reported by the patients. RESULTS: The CAP wound dressing was superior to the control (p < 0.001) in the improvement of 3 wound parameters, that is, deep tissue oxygen saturation, hemoglobin distribution, and tissue water distribution. CAP was well tolerated, and pain levels were lower in CAP-treated wound areas. CONCLUSION: CAP wound dressing is a promising new tool for acute wound healing.

Effect on healing rates of wounds treated with direct cold atmospheric plasma: a case series.

OBJECTIVE: The response of different critical acute and hard-to-heal wounds to an innovative wound care modality-direct application of cold atmospheric plasma (CAP)-was investigated in this clinical case series. METHOD: Over an observation period of two years, acute wounds with at least one risk factor for chronification, as well as hard-to-heal wounds were treated for 180 seconds three times per week with CAP. CAP treatment was additional to standard wound care. Photographs were taken for wound documentation. The wound sizes before the first CAP treatment, after four weeks, after 12 weeks and at wound closure/end of observation time were determined using image processing software, and analysed longitudinally for the development of wound size. RESULTS: A total of 27 wounds (19 hard-to-heal and eight acute wounds) with a mean wound area of 15cm2 and a mean wound age of 49 months were treated with CAP and analysed. All (100%) of the acute wounds and 68% of the hard-to-heal wounds healed after an average treatment duration of 14.2 weeks. At the end of the observation period, 21% of hard-to-heal wounds were not yet closed but were reduced in size by >80%. In 11% of the hard-to-heal wounds (n=2) therapy failed. CONCLUSION: The results suggested a beneficial effect of additional CAP therapy on wound healing. DECLARATION OF INTEREST: This work was carried out within the research projects 'Plasma for Life' (funding reference no. 13FH6I04IA) with financial support from the German Federal Ministry of Education and Research (BMBF). In the past seven years AFS has provided consulting services to Evonik and has received institutional support by Heraeus, Johnson & Johnson and Evonik. There are no royalties to disclose. The Department for Trauma Surgery, Orthopaedics and Plastic Surgery received charitable donations by CINOGY GmbH. CINOGY GmbH released the di_CAP devices and electrodes for the study. WV and AH were involved in the development of the used di_CAP device (Plasmaderm, CINOGY GmbH). WV is shareholder of the outsourced start-up company CINOGY GmbH.