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- ItemNonspherical Nanoparticle Shape Stability Is Affected by Complex Manufacturing Aspects: Its Implications for Drug Delivery and Targeting(Weinheim : Wiley-VCH, 2019) Haryadi, Bernard Manuel; Hafner, Daniel; Amin, Ihsan; Schubel, Rene; Jordan, Rainer; Winter, Gerhard; Engert, JuliaThe shape of nanoparticles is known recently as an important design parameter influencing considerably the fate of nanoparticles with and in biological systems. Several manufacturing techniques to generate nonspherical nanoparticles as well as studies on in vitro and in vivo effects thereof have been described. However, nonspherical nanoparticle shape stability in physiological-related conditions and the impact of formulation parameters on nonspherical nanoparticle resistance still need to be investigated. To address these issues, different nanoparticle fabrication methods using biodegradable polymers are explored to produce nonspherical nanoparticles via the prevailing film-stretching method. In addition, systematic comparisons to other nanoparticle systems prepared by different manufacturing techniques and less biodegradable materials (but still commonly utilized for drug delivery and targeting) are conducted. The study evinces that the strong interplay from multiple nanoparticle properties (i.e., internal structure, Young's modulus, surface roughness, liquefaction temperature [glass transition (Tg) or melting (Tm)], porosity, and surface hydrophobicity) is present. It is not possible to predict the nonsphericity longevity by merely one or two factor(s). The most influential features in preserving the nonsphericity of nanoparticles are existence of internal structure and low surface hydrophobicity (i.e., surface-free energy (SFE) > ≈55 mN m−1, material–water interfacial tension <6 mN m−1), especially if the nanoparticles are soft (<1 GPa), rough (Rrms > 10 nm), porous (>1 m2 g−1), and in possession of low bulk liquefaction temperature (<100 °C). Interestingly, low surface hydrophobicity of nanoparticles can be obtained indirectly by the significant presence of residual stabilizers. Therefore, it is strongly suggested that nonsphericity of particle systems is highly dependent on surface chemistry but cannot be appraised separately from other factors. These results and reviews allot valuable guidelines for the design and manufacturing of nonspherical nanoparticles having adequate shape stability, thereby appropriate with their usage purposes. Furthermore, they can assist in understanding and explaining the possible mechanisms of nonspherical nanoparticles effectivity loss and distinctive material behavior at the nanoscale. © 2019 The Authors. Published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
- ItemNon-touching plasma–liquid interaction – where is aqueous nitric oxide generated?(Cambridge : RSC Publ., 2018) Jablonowski, Helena; Schmidt-Bleker, Ansgar; Weltmann, Klaus-Dieter; von Woedtke, Thomas; Wende, KristianMass transport through graphene is receiving increasing attention due to the potential for molecular sieving. Experimental studies are mostly limited to the translocation of protons, ions, and water molecules, and results for larger molecules through graphene are rare. Here, we perform controlled radical polymerization with surface-anchored self-assembled initiator monolayer in a monomer solution with single-layer graphene separating the initiator from the monomer. We demonstrate that neutral monomers are able to pass through the graphene (via native defects) and increase the graphene defects ratio (Raman ID/IG) from ca. 0.09 to 0.22. The translocations of anionic and cationic monomers through graphene are significantly slower due to chemical interactions of monomers with the graphene defects. Interestingly, if micropatterned initiator-monolayers are used, the translocations of anionic monomers apparently cut the graphene sheet into congruent microscopic structures. The varied interactions between monomers and graphene defects are further investigated by quantum molecular dynamics simulations.
- ItemFrom patent to product? 50 years of low-pressure plasma sterilization(Weinheim : Wiley-VCH, 2018-10-18) Fiebrandt, Marcel; Lackmann, Jan-Wilm; Stapelmann, KatharinaThe development of new sterilization methods is still a major topic. The need for new techniques arises from the development of new instruments and the usage of different materials. Especially in the case of plastics with their beneficial properties, for example, in the field of implantology, plasma sterilization is seen as a promising alternative to the standard methods. However, 50 years after the first patent and although low-pressure plasmas show excellent inactivation performance (>log 6 reduction), only one commercial system is available on the market for a distinct application. We will give a short review about known plasma sterilization mechanisms, the different plasma sterilization systems in use, analyze possible challenges for an industrial process and comment on possible solutions for a broader acceptance and utilization of low-pressure plasma sterilization.
- ItemWhite paper on plasma for medicine and hygiene: Future in plasma health sciences(Hoboken, NJ : Wiley Interscience, 2019) Bekeschus, Sander; Favia, Pietro; Robert, Eric; von Woedtke, ThomasPlasma Science and Technology offer their valuable contribution to human health since more than 50 years, after decades of experiences in the field of biomaterials; and more than a decade in using plasmas for therapeutic uses in medicine. Current knowledge as well as key challenges and opportunities for the human health have been intensely discussed during the Future in Plasma Science II (FIPS II) workshop in February 2016 in Greifswald, Germany. This contribution summarizes the major outcomes of the meeting and the current literature and consensus with an emphasis on major challenges in the fields of Plasma Science and Technology for improving human health.
- ItemAbout the Development and Dynamics of Microdischarges in Toluene-Containing Air(Dordrecht : Springer Science + Business Media B.V., 2019) Brandenburg, Ronny; Jahanbakhsh, Sina; Schiorlin, Milko; Schmidt, MichaelThe development of microdischarges and the inception dynamics of subsequent microdischarges in an electrode arrangement consisting of a metal pin and a hemispherical dielectric-covered electrode, operated in air with a small toluene admixture, is studied. The discharge is operated with sinusoidal high voltage. A gated ICCD camera and a current probe enable the recording of images and current pulses of the single microdischarges, respectively, while the spatio-temporally resolved development is measured with a multi-dimensional time-correlated single photon counting technique. The overall discharge dynamics changes significantly if a concentration of 35 ppm toluene is added to dry air. A lower high voltage amplitude than in dry air is needed for stable discharge operation. This can be explained by the lower ionization energy of toluene compared to molecular oxygen and nitrogen. The microdischarge development is the same with or without admixture, i.e. a positive (cathode directed) streamer mechanism is observed. Lower mean power is dissipated into the discharge when toluene is admixed. The main effect caused by toluene admixture is the suppression of high-energy microdischarges in case of the cathodic pin half-cycle of the sinusoidal high voltage. The influence on the inception voltage by additional ionization mechanisms and volume memory effects, the consumption of energetic electrons for toluene decomposition reactions, and the modification of the surface by plasma treatment are discussed as possible reasons.
- ItemA Comparison of Floating-Electrode DBD and kINPen Jet: Plasma Parameters to Achieve Similar Growth Reduction in Colon Cancer Cells Under Standardized Conditions(Dordrecht : Springer Science + Business Media B.V., 2017-9-6) Bekeschus, Sander; Lin, Abraham; Fridman, Alexander; Wende, Kristian; Weltmann, Klaus-Dieter; Miller, VandanaA comparative study of two plasma sources (floating-electrode dielectric barrier discharge, DBD, Drexel University; atmospheric pressure argon plasma jet, kINPen, INP Greifswald) on cancer cell toxicity was performed. Cell culture protocols, cytotoxicity assays, and procedures for assessment of hydrogen peroxide (H2O2) were standardized between both labs. The inhibitory concentration 50 (IC50) and its corresponding H2O2 deposition was determined for both devices. For the DBD, IC50 and H2O2 generation were largely dependent on the total energy input but not pulsing frequency, treatment time, or total number of cells. DBD cytotoxicity could not be replicated by addition of H2O2 alone and was inhibited by larger amounts of liquid present during the treatment. Jet plasma toxicity depended on peroxide generation as well as total cell number and amount of liquid. Thus, the amount of liquid present during plasma treatment in vitro is key in attenuating short-lived species or other physical effects from plasmas. These in vitro results suggest a role of liquids in or on tissues during plasma treatment in a clinical setting. Additionally, we provide a platform for correlation between different plasma sources for a predefined cellular response.
- ItemOne Year Follow-Up Risk Assessment in SKH-1 Mice and Wounds Treated with an Argon Plasma Jet(Basel : Molecular Diversity Preservation International, 2017-4-19) Schmidt, Anke; von Woedtke, Thomas; Stenzel, Jan; Lindner, Tobias; Polei, Stefan; Vollmar, Brigitte; Bekeschus, SanderMultiple evidence in animal models and in humans suggest a beneficial role of cold physical plasma in wound treatment. Yet, risk assessment studies are important to further foster therapeutic advancement and acceptance of cold plasma in clinics. Accordingly, we investigated the long-term side effects of repetitive plasma treatment over 14 consecutive days in a rodent full-thickness ear wound model. Subsequently, animals were housed for 350 days and sacrificed thereafter. In blood, systemic changes of the pro-inflammatory cytokines interleukin 1β and tumor necrosis factor α were absent. Similarly, tumor marker levels of α-fetoprotein and calcitonin remained unchanged. Using quantitative PCR, the expression levels of several cytokines and tumor markers in liver, lung, and skin were found to be similar in the control and treatment group as well. Likewise, histological and immunohistochemical analysis failed to detect abnormal morphological changes and the presence of tumor markers such as carcinoembryonic antigen, α-fetoprotein, or the neighbor of Punc 11. Absence of neoplastic lesions was confirmed by non-invasive imaging methods such as anatomical magnetic resonance imaging and positron emission tomography-computed tomography. Our results suggest that the beneficial effects of cold plasma in wound healing come without apparent side effects including tumor formation or chronic inflammation.
- ItemCold Atmospheric Plasma in the Treatment of Osteosarcoma(Basel : Molecular Diversity Preservation International, 2017-9-19) Gümbel, Denis; Bekeschus, Sander; Gelbrich, Nadine; Napp, Matthias; Ekkernkamp, Axel; Kramer, Axel; Stope, Matthias B.Human osteosarcoma (OS) is the most common primary malignant bone tumor occurring most commonly in adolescents and young adults. Major improvements in disease-free survival have been achieved by implementing a combination therapy consisting of radical surgical resection of the tumor and systemic multi-agent chemotherapy. However, long-term survival remains poor, so novel targeted therapies to improve outcomes for patients with osteosarcoma remains an area of active research. This includes immunotherapy, photodynamic therapy, or treatment with nanoparticles. Cold atmospheric plasma (CAP), a highly reactive (partially) ionized physical state, has been shown to inherit a significant anticancer capacity, leading to a new field in medicine called “plasma oncology.” The current article summarizes the potential of CAP in the treatment of human OS and reviews the underlying molecular mode of action.
- ItemA Neutrophil Proteomic Signature in Surgical Trauma Wounds(Basel : Molecular Diversity Preservation International, 2018-3-7) Bekeschus, Sander; Lackmann, Jan-Wilm; Gümbel, Denis; Napp, Matthias; Schmidt, Anke; Wende, KristianNon-healing wounds continue to be a clinical challenge for patients and medical staff. These wounds have a heterogeneous etiology, including diabetes and surgical trauma wounds. It is therefore important to decipher molecular signatures that reflect the macroscopic process of wound healing. To this end, we collected wound sponge dressings routinely used in vacuum assisted therapy after surgical trauma to generate wound-derived protein profiles via global mass spectrometry. We confidently identified 311 proteins in exudates. Among them were expected targets belonging to the immunoglobulin superfamily, complement, and skin-derived proteins, such as keratins. Next to several S100 proteins, chaperones, heat shock proteins, and immune modulators, the exudates presented a number of redox proteins as well as a discrete neutrophil proteomic signature, including for example cathepsin G, elastase, myeloperoxidase, CD66c, and lipocalin 2. We mapped over 200 post-translational modifications (PTMs; cysteine/methionine oxidation, tyrosine nitration, cysteine trioxidation) to the proteomic profile, for example, in peroxiredoxin 1. Investigating manually collected exudates, we confirmed presence of neutrophils and their products, such as microparticles and fragments containing myeloperoxidase and DNA. These data confirmed known and identified less known wound proteins and their PTMs, which may serve as resource for future studies on human wound healing.
- ItemPlasma 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, BirgitBiomaterials 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.