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.

Download Full-text

Inhibitory Effect of Cold Atmospheric Plasma on Chronic Wound-Related Multispecies Biofilms

Applied Sciences ◽

10.3390/app11125441 ◽

2021 ◽

Vol 11 (12) ◽

pp. 5441

Author(s):

Maria Alcionéia Carvalho de Oliveira ◽

Gabriela de Morais Gouvêa Lima ◽

Thalita M. Castaldelli Nishime ◽

Aline Vidal Lacerda Gontijo ◽

Beatriz Rossi Canuto de Menezes ◽

...

Keyword(s):

Mammalian Cells ◽

Wound Care ◽

Healing Process ◽

Inhibitory Effect ◽

Atmospheric Plasma ◽

Effective Parameters ◽

Cold Atmospheric Plasma ◽

Low Cytotoxicity ◽

Collagen Membranes ◽

Multispecies Biofilms

The presence of microbial biofilms in the wounds affects negatively the healing process and can contribute to therapeutic failures. This study aimed to establish the effective parameters of cold atmospheric plasma (CAP) against wound-related multispecies and monospecies biofilms, and to evaluate the cytotoxicity and genotoxicity of the protocol. Monospecies and multispecies biofilms were formed by methicillin-resistant Staphylococcus aureus (MRSA), Pseudomonas aeruginosa and Enterococcus faecalis. The monospecies biofilms were grown in 96 wells plates and multispecies biofilm were formed on collagen membranes. The biofilms were exposed to helium CAP for 1, 3, 5 and 7 min. In monospecies biofilms, the inhibitory effect was detected after 1 min of exposure for E. faecalis and after 3 min for MRSA. A reduction in P. aeruginosa biofilm’s viability was detected after 7 min of exposure. For the multispecies biofilms, the reduction in the overall viability was detected after 5 min of exposure to CAP. Additionally, cytotoxicity and genotoxicity were evaluated by MTT assay and static cytometry, respectively. CAP showed low cytotoxicity and no genotoxicity to mouse fibroblastic cell line (3T3). It could be concluded that He-CAP showed inhibitory effect on wound-related multispecies biofilms, with low cytotoxicity and genotoxicity to mammalian cells. These findings point out the potential application of CAP in wound care.

Download Full-text

Wound bed preparation: a case series using polyhexanide and betaine solution and gel—a UK perspective

Journal of Wound Care ◽

10.12968/jowc.2020.29.7.380 ◽

2020 ◽

Vol 29 (7) ◽

pp. 380-386

Author(s):

Leanne Atkin ◽

John Stephenson ◽

Dawn M Cooper

Keyword(s):

Chronic Wounds ◽

Wound Care ◽

Case Series ◽

Wound Irrigation ◽

Irrigation Solution ◽

New Treatment ◽

The Uk ◽

Wound Bed Preparation ◽

Dressing Change ◽

Observation Period

Objective: The burden of wound care within the NHS is estimated at a cost of £5.3 billion per year and is set to rise annually by 30%. This case series describes the results of using polyhexanide (PHMB) and betaine wound irrigation solution and gels (Prontosan, B.Braun Medical Ltd., UK) across the UK in hard-to-heal (also described as chronic) wounds up to 20 years' duration, with an observation period of greater than one month. Over half of the hard-to-heal wounds were healed and vast improvements to all other wounds were observed. Improvements to wound bed condition were reported as early as two days after commencing initial treatment, with decreases in malodour, exudate, slough and pain reported across the case series. In addition to wound bed improvements, a reduction in dressing change frequency of 55% was observed in hard-to-heal wounds under the new treatment regime.

Download Full-text

Targeting Protective Catalase of Tumor Cells with Cold Atmospheric Plasma- Activated Medium (PAM)

Anti-Cancer Agents in Medicinal Chemistry ◽

10.2174/1871520617666170801103708 ◽

2018 ◽

Vol 18 (6) ◽

pp. 784-804 ◽

Cited By ~ 18

Author(s):

Georg Bauer

Keyword(s):

Control System ◽

Singlet Oxygen ◽

Tumor Cells ◽

Plasma Potential ◽

Atmospheric Plasma ◽

Antitumor Action ◽

Active Principle ◽

Reaction Products ◽

Cold Atmospheric Plasma

Background: Application of cold atmospheric plasma to medium generates “plasma-activated medium” that induces apoptosis selectively in tumor cells and that has an antitumor effect in vivo. The underlying mechanisms are not well understood. Objective: Elucidation of potential chemical interactions within plasma-activated medium and of reactions of medium components with specific target structures of tumor cells should allow to define the active principle in plasma activated medium. Methods: Established knowledge of intercellular apoptosis-inducing reactive oxygen/nitrogen species-dependent signaling and its control by membrane-associated catalase and SOD was reviewed. Model experiments using extracellular singlet oxygen were analyzed with respect to catalase inactivation and their relevance for the antitumor action of cold atmospheric plasma. Potential interactions of this tumor cell-specific control system with components of plasma-activated medium or its reaction products were discussed within the scope of the reviewed signaling principles. Results: None of the long-lived species found in plasma-activated medium, such as nitrite and H2O2, nor OCl- or .NO seemed to have the potential to interfere with catalase-dependent control of apoptosis-inducing signaling of tumor cells when acting alone. However, the combination of H2O2 and nitrite might generate peroxynitrite. The protonation of peroxnitrite to peroxynitrous acid allows for the generation of hydroxyl radicals that react with H2O2, leading to the formation of hydroperoxide radicals. These allow for singlet oxygen generation and inactivation of membrane-associated catalase through an autoamplificatory mechanism, followed by intercellular apoptosis-inducing signaling. Conclusion: Nitrite and H2O2 in plasma-activated medium establish singlet oxygen-dependent interference selectively with the control system of tumor cells.

Download Full-text

The Application of the Cold Atmospheric Plasma-Activated Solutions in Cancer Treatment

Anti-Cancer Agents in Medicinal Chemistry ◽

10.2174/1871520617666170731115233 ◽

2018 ◽

Vol 18 (6) ◽

pp. 769-775 ◽

Cited By ~ 13

Author(s):

Dayun Yan ◽

Jonathan H. Sherman ◽

Michael Keidar

Keyword(s):

Cancer Treatment ◽

Atmospheric Plasma ◽

Current Status ◽

Cold Atmospheric Plasma ◽

Anti Cancer ◽

Long Time ◽

Key Topics ◽

The Common

Background: Over the past five years, the cold atmospheric plasma-activated solutions (PAS) have shown their promissing application in cancer treatment. Similar as the common direct cold plasma treatment, PAS shows a selective anti-cancer capacity in vitro and in vivo. However, different from the direct cold atmospheric plasma (CAP) treatment, PAS can be stored for a long time and can be used without dependence on a CAP device. The research on PAS is gradually becoming a hot topic in plasma medicine. Objectives: In this review, we gave a concise but comprehensive summary on key topics about PAS including the development, current status, as well as the main conclusions about the anti-cancer mechanism achieved in past years. The approaches to make strong and stable PAS are also summarized.

Download Full-text

A map of control for cold atmospheric plasma jets: From physical mechanisms to optimizations

Applied Physics Reviews ◽

10.1063/5.0022534 ◽

2021 ◽

Vol 8 (1) ◽

pp. 011306

Author(s):

Li Lin ◽

Michael Keidar

Keyword(s):

Plasma Jets ◽

Atmospheric Plasma ◽

Cold Atmospheric Plasma ◽

Physical Mechanisms

Download Full-text

Tiny Cold Atmospheric Plasma Jet for Biomedical Applications

Processes ◽

10.3390/pr9020249 ◽

2021 ◽

Vol 9 (2) ◽

pp. 249

Author(s):

Zhitong Chen ◽

Richard Obenchain ◽

Richard E. Wirz

Keyword(s):

Biomedical Applications ◽

Plasma Jet ◽

Discharge Voltage ◽

Plasma Jets ◽

Atmospheric Plasma ◽

Physical Parameters ◽

Cold Atmospheric Plasma ◽

Water Metal ◽

Plasma Probe ◽

Jet Nozzle

Conventional plasma jets for biomedical applications tend to have several drawbacks, such as high voltages, high gas delivery, large plasma probe volume, and the formation of discharge within the organ. Therefore, it is challenging to employ these jets inside a living organism’s body. Thus, we developed a single-electrode tiny plasma jet and evaluated its use for clinical biomedical applications. We investigated the effect of voltage input and flow rate on the jet length and studied the physical parameters of the plasma jet, including discharge voltage, average gas and subject temperature, and optical emissions via spectroscopy (OES). The interactions between the tiny plasma jet and five subjects (de-ionized (DI) water, metal, cardboard, pork belly, and pork muscle) were studied at distances of 10 mm and 15 mm from the jet nozzle. The results showed that the tiny plasma jet caused no damage or burning of tissues, and the ROS/RNS (reactive oxygen/nitrogen species) intensity increased when the distance was lowered from 15 mm to 10 mm. These initial observations establish the tiny plasma jet device as a potentially useful tool in clinical biomedical applications.

Download Full-text

The synergistic effect of Canady Helios cold atmospheric plasma and a FOLFIRINOX regimen for the treatment of cholangiocarcinoma in vitro

Scientific Reports ◽

10.1038/s41598-021-88451-w ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Olivia Jones ◽

Xiaoqian Cheng ◽

Saravana R. K. Murthy ◽

Lawan Ly ◽

Taisen Zhuang ◽

...

Keyword(s):

Cell Viability ◽

Chemotherapy Regimen ◽

Synergetic Effect ◽

Atmospheric Plasma ◽

High Recurrence Rate ◽

Cold Atmospheric Plasma ◽

Tract Cancer ◽

Anticancer Properties ◽

Potential Interactions

AbstractCholangiocarcinoma (CCA) is a rare biliary tract cancer with a low five-year survival rate and high recurrence rate after surgical resection. Currently treatment approaches include systemic chemotherapeutics such as FOLFIRINOX, a chemotherapy regimen is a possible treatment for severe CCA cases. A limitation of this chemotherapy regimen is its toxicity to patients and adverse events. There exists a need for therapies to alleviate the toxicity of a FOLFIRINOX regimen while enhancing or not altering its anticancer properties. Cold atmospheric plasma (CAP) is a technology with a promising future as a selective cancer treatment. It is critical to know the potential interactions between CAP and adjuvant chemotherapeutics. In this study the aim is to characterize the efficacy of FOLFIRINOX and CAP in combination to understand potential synergetic effect on CCA cells. FOLFIRINOX treatment alone at the highest dose tested (53.8 µM fluorouracil, 13.7 µM Leucovorin, 5.1 µM Irinotecan, and 3.7 µM Oxaliplatin) reduced CCA cell viability to below 20% while CAP treatment alone for 7 min reduced viability to 3% (p < 0.05). An analysis of cell viability, proliferation, and cell cycle demonstrated that CAP in combination with FOLFIRINOX is more effective than either treatment alone at a lower FOLFIRINOX dose of 6.7 µM fluorouracil, 1.7 µM leucovorin, 0.6 µM irinotecan, and 0.5 µM oxaliplatin and a shorter CAP treatment of 1, 3, or 5 min. In conclusion, CAP has the potential to reduce the toxicity burden of FOLFIRINOX and warrants further investigation as an adjuvant therapy.

Download Full-text