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    Gas Plasma-Augmented Wound Healing in Animal Models and Veterinary Medicine
    (Basel : MDPI, 2021) Bekeschus, Sander; Kramer, Axel; Schmidt, Anke
    The loss of skin integrity is inevitable in life. Wound healing is a necessary sequence of events to reconstitute the body’s integrity against potentially harmful environmental agents and restore homeostasis. Attempts to improve cutaneous wound healing are therefore as old as humanity itself. Furthermore, nowadays, targeting defective wound healing is of utmost importance in an aging society with underlying diseases such as diabetes and vascular insufficiencies being on the rise. Because chronic wounds’ etiology and specific traits differ, there is widespread polypragmasia in targeting non-healing conditions. Reactive oxygen and nitrogen species (ROS/RNS) are an overarching theme accompanying wound healing and its biological stages. ROS are signaling agents generated by phagocytes to inactivate pathogens. Although ROS/RNS’s central role in the biology of wound healing has long been appreciated, it was only until the recent decade that these agents were explicitly used to target defective wound healing using gas plasma technology. Gas plasma is a physical state of matter and is a partially ionized gas operated at body temperature which generates a plethora of ROS/RNS simultaneously in a spatiotemporally controlled manner. Animal models of wound healing have been vital in driving the development of these wound healing-promoting technologies, and this review summarizes the current knowledge and identifies open ends derived from in vivo wound models under gas plasma therapy. While gas plasma-assisted wound healing in humans has become well established in Europe, veterinary medicine is an emerging field with great potential to improve the lives of suffering animals.
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    Combined toxicity of gas plasma treatment and nanoparticles exposure in melanoma cells in vitro
    (Basel : MDPI, 2021) Bekeschus, Sander
    Despite continuous advances in therapy, cancer remains a deadly disease. Over the past years, gas plasma technology emerged as a novel tool to target tumors, especially skin. Another promising anticancer approach are nanoparticles. Since combination therapies are becoming increas-ingly relevant in oncology, both gas plasma treatment and nanoparticle exposure were combined. A series of nanoparticles were investigated in parallel, namely, silica, silver, iron oxide, cerium oxide, titanium oxide, and iron-doped titanium oxide. For gas plasma treatment, the atmospheric pressure argon plasma jet kINPen was utilized. Using three melanoma cell lines, the two murine non-metastatic B16F0 and metastatic B16F10 cells and the human metastatic B-Raf mutant cell line SK-MEL-28, the combined cytotoxicity of both approaches was identified. The combined cytotoxicity of gas plasma treatment and nanoparticle exposure was consistent across all three cell lines for silica, silver, iron oxide, and cerium oxide. In contrast, for titanium oxide and iron-doped titanium oxide, significantly combined cytotoxicity was only observed in B16F10 cells.
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    Combining Biocompatible and Biodegradable Scaffolds and Cold Atmospheric Plasma for Chronic Wound Regeneration
    (Basel : Molecular Diversity Preservation International (MDPI), 2021) Emmert, Steffen; Pantermehl, Sven; Foth, Aenne; Waletzko-Hellwig, Janine; Hellwig, Georg; Bader, Rainer; Illner, Sabine; Grabow, Niels; Bekeschus, Sander; Weltmann, Klaus-Dieter; Jung, Ole; Boeckmann, Lars
    Skin regeneration is a quite complex process. Epidermal differentiation alone takes about 30 days and is highly regulated. Wounds, especially chronic wounds, affect 2% to 3% of the elderly population and comprise a heterogeneous group of diseases. The prevailing reasons to develop skin wounds include venous and/or arterial circulatory disorders, diabetes, or constant pressure to the skin (decubitus). The hallmarks of modern wound treatment include debridement of dead tissue, disinfection, wound dressings that keep the wound moist but still allow air exchange, and compression bandages. Despite all these efforts there is still a huge treatment resistance and wounds will not heal. This calls for new and more efficient treatment options in combination with novel biocompatible skin scaffolds. Cold atmospheric pressure plasma (CAP) is such an innovative addition to the treatment armamentarium. In one CAP application, antimicrobial effects, wound acidification, enhanced microcirculations and cell stimulation can be achieved. It is evident that CAP treatment, in combination with novel bioengineered, biocompatible and biodegradable electrospun scaffolds, has the potential of fostering wound healing by promoting remodeling and epithelialization along such temporarily applied skin replacement scaffolds.
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    Biocompatible Gas Plasma Treatment Affects Secretion Profiles but Not Osteogenic Differentiation in Patient-Derived Mesenchymal Stromal Cells
    (Basel : Molecular Diversity Preservation International (MDPI), 2022) Fischer, Maximilian; Schoon, Janosch; Freund, Eric; Miebach, Lea; Weltmann, Klaus-Dieter; Bekeschus, Sander; Wassilew, Georgi I.
    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.