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Author: Rebl, Henrike × Version: publishedVersion ×

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    Molecular mechanisms of the efficacy of cold atmospheric pressure plasma (CAP) in cancer treatment
    (Basel : MDPI AG, 2020) Semmler, Marie Luise; Bekeschus, Sander; Schäfer, Mirijam; Bernhardt, Thoralf; Fischer, Tobias; Witzke, Katharina; Seebauer, Christian; Rebl, Henrike; Grambow, Eberhard; Vollmar, Brigitte; Nebe, J. Barbara; Metelmann, Hans-Robert; Woedtke, Thomas von; Emmert, Steffen; Boeckmann, Lars
    Recently, the potential use of cold atmospheric pressure plasma (CAP) in cancer treatment has gained increasing interest. Especially the enhanced selective killing of tumor cells compared to normal cells has prompted researchers to elucidate the molecular mechanisms for the efficacy of CAP in cancer treatment. This review summarizes the current understanding of how CAP triggers intracellular pathways that induce growth inhibition or cell death. We discuss what factors may contribute to the potential selectivity of CAP towards cancer cells compared to their non-malignant counterparts. Furthermore, the potential of CAP to trigger an immune response is briefly discussed. Finally, this overview demonstrates how these concepts bear first fruits in clinical applications applying CAP treatment in head and neck squamous cell cancer as well as actinic keratosis. Although significant progress towards understanding the underlying mechanisms regarding the efficacy of CAP in cancer treatment has been made, much still needs to be done with respect to different treatment conditions and comparison of malignant and non-malignant cells of the same cell type and same donor. Furthermore, clinical pilot studies and the assessment of systemic effects will be of tremendous importance towards bringing this innovative technology into clinical practice. © 2020 by the authors. Licensee MDPI, Basel, Switzerland.
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    Enhanced calcium ion mobilization in osteoblasts on amino group containing plasma polymer nanolayer
    (London : BioMed Central, 2018-3-21) Staehlke, Susanne; Rebl, Henrike; Finke, Birgit; Mueller, Petra; Gruening, Martina; Nebe, J. Barbara
    Background: Biomaterial modifications—chemical and topographical—are of particular importance for the integration of materials in biosystems. Cells are known to sense these biomaterial characteristics, but it has remained unclear which physiological processes bio modifications trigger. Hence, the question arises of whether the dynamic of intracellular calcium ions is important for the characterization of the cell–material interaction. In our prior research we could demonstrate that a defined geometrical surface topography affects the cell physiology; this was finally detectable in a reduced intracellular calcium mobilization after the addition of adenosine triphosphate (ATP). Results: This new contribution examines the cell physiology of human osteoblasts concerning the relative cell viability and the calcium ion dynamic on different chemical modifications of silicon–titanium (Ti) substrates. Chemical modifications comprising the coating of Ti surfaces with a plasma polymerized allylamine (PPAAm)-layer or with a thin layer of collagen type-I were compared with a bare Ti substrate as well as tissue culture plastic. For this purpose, the human osteoblasts (MG-63 and primary osteoblasts) were seeded onto the surfaces for 24 h. The relative cell viability was determined by colorimetric measurements of the cell metabolism and relativized to the density of cells quantified using crystal violet staining. The calcium ion dynamic of osteoblasts was evaluated by the calcium imaging analysis of fluo-3 stained vital cells using a confocal laser scanning microscope. The positively charged nano PPAAm-layer resulted in enhanced intracellular calcium ion mobilization after ATP-stimulus and cell viability. This study underlines the importance of the calcium signaling for the manifestation of the cell physiology. Conclusions: Our current work provides new insights into the intracellular calcium dynamic caused by diverse chemical surface compositions. The calcium ion dynamic appears to be a sensitive parameter for the cell physiology and, thus, may represent a useful approach for evaluating a new biomaterial. In this regard, reliable in vitro-tests of cell behavior at the interface to a material are crucial steps in securing the success of a new biomaterial in medicine.
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    Restricted cell functions on micropillars are alleviated by surface-nanocoating with amino groups
    (Cambridge : Company of Biologists Limited, 2018) Moerke, Caroline; Staehlke, Susanne; Rebl, Henrike; Finke, Birgit; Nebe, J. Barbara
    The topographical and chemical surface features of biomaterials are sensed by the cells, affecting their physiology at the interface. When placed on titanium, we recently discovered osteoblasts attempted caveolae-mediated phagocytosis of the sharp-edged microstructures. This active, energy-consuming process resulted in decreased osteoblastic cell functions (e.g. secretion of extracellular matrix proteins). However, chemical modification with plasma polymerized allylamine (PPAAm) was able to amplify osteoblast adhesion and spreading, resulting in better implant osseointegration in vivo. In the present in vitro study, we analyzed whether this plasma polymer nanocoating is able to attenuate the microtopography-induced changes of osteoblast physiology. On PPAAm, we found cells showed a higher cell interaction with the geometrical micropillars by 30 min, and a less distinct reduction in the mRNA expression of collagen type I, osteocalcin and fibronectin after 24 h of cell growth. Interestingly, the cells were more active and sensitive on PPAAm-coated micropillars, and react with a substantial Ca2+ ion mobilization after stimulation with ATP. These results highlight that it is important for osteoblasts to establish cell surface contact for them to perform their functions.
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    Plasma polymerized allylamine-the unique cell-attractive nanolayer for dental implant materials
    (Basel : MDPI, 2019) Nebe, J. Barbara; Rebl, Henrike; Schlosser, Michael; Staehlke, Susanne; Gruening, Martina; Weltmann, Klaus-Dieter; Walschus, Uwe; Finke, Birgit
    Biomaterials should be bioactive in stimulating the surrounding tissue to accelerate the ingrowth of permanent implants. Chemical and topographical features of the biomaterial surface affect cell physiology at the interface. A frequently asked question is whether the chemistry or the topography dominates the cell-material interaction. Recently, we demonstrated that a plasma-chemical modification using allylamine as a precursor was able to boost not only cell attachment and cell migration, but also intracellular signaling in vital cells. This microwave plasma process generated a homogenous nanolayer with randomly distributed, positively charged amino groups. In contrast, the surface of the human osteoblast is negatively charged at −15 mV due to its hyaluronan coat. As a consequence, we assumed that positive charges at the material surface—provoking electrostatic interaction forces—are attractive for the first cell encounter. This plasma-chemical nanocoating can be used for several biomaterials in orthopedic and dental implantology like titanium, titanium alloys, calcium phosphate scaffolds, and polylactide fiber meshes produced by electrospinning. In this regard, we wanted to ascertain whether plasma polymerized allylamine (PPAAm) is also suitable for increasing the attractiveness of a ceramic surface for dental implants using Yttria-stabilized tetragonal zirconia.