TY - JOUR A1 - Christ, Bastian A1 - Glaubitt, Walther A1 - Berberich, Katrin A1 - Weigel, Tobias A1 - Probst, Jörn A1 - Sextl, Gerhard A1 - Dembski, Sofia T1 - Sol-gel-derived fibers based on amorphous α-hydroxy-carboxylate-modified titanium(IV) oxide as a 3-dimensional scaffold JF - Materials N2 - The development of novel fibrous biomaterials and further processing of medical devices is still challenging. For instance, titanium(IV) oxide is a well-established biocompatible material, and the synthesis of TiO\(_x\) particles and coatings via the sol-gel process has frequently been published. However, synthesis protocols of sol-gel-derived TiO\(_x\) fibers are hardly known. In this publication, the authors present a synthesis and fabrication of purely sol-gel-derived TiO\(_x\) fiber fleeces starting from the liquid sol-gel precursor titanium ethylate (TEOT). Here, the α-hydroxy-carboxylic acid lactic acid (LA) was used as a chelating ligand to reduce the reactivity towards hydrolysis of TEOT enabling a spinnable sol. The resulting fibers were processed into a non-woven fleece, characterized with FTIR, \(^{13}\)C-MAS-NMR, XRD, and screened with regard to their stability in physiological solution. They revealed an unexpected dependency between the LA content and the dissolution behavior. Finally, in vitro cell culture experiments proved their potential suitability as an open-mesh structured scaffold material, even for challenging applications such as therapeutic medicinal products (ATMPs). KW - sol-gel chemistry KW - scaffold KW - dry spinning Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-270694 SN - 1996-1944 VL - 15 IS - 8 ER - TY - JOUR A1 - Eder, Sascha A1 - Hollmann, Claudia A1 - Mandasari, Putri A1 - Wittmann, Pia A1 - Schumacher, Fabian A1 - Kleuser, Burkhard A1 - Fink, Julian A1 - Seibel, Jürgen A1 - Schneider-Schaulies, Jürgen A1 - Stigloher, Christian A1 - Beyersdorf, Niklas A1 - Dembski, Sofia T1 - Synthesis and characterization of ceramide-containing liposomes as membrane models for different T cell subpopulations JF - Journal of Functional Biomaterials N2 - A fine balance of regulatory (T\(_{reg}\)) and conventional CD4\(^+\) T cells (T\(_{conv}\)) is required to prevent harmful immune responses, while at the same time ensuring the development of protective immunity against pathogens. As for many cellular processes, sphingolipid metabolism also crucially modulates the T\(_{reg}\)/T\(_{conv}\) balance. However, our understanding of how sphingolipid metabolism is involved in T cell biology is still evolving and a better characterization of the tools at hand is required to advance the field. Therefore, we established a reductionist liposomal membrane model system to imitate the plasma membrane of mouse T\(_{reg}\) and T\(_{conv}\) with regards to their ceramide content. We found that the capacity of membranes to incorporate externally added azide-functionalized ceramide positively correlated with the ceramide content of the liposomes. Moreover, we studied the impact of the different liposomal preparations on primary mouse splenocytes in vitro. The addition of liposomes to resting, but not activated, splenocytes maintained viability with liposomes containing high amounts of C\(_{16}\)-ceramide being most efficient. Our data thus suggest that differences in ceramide post-incorporation into T\(_{reg}\) and T\(_{conv}\) reflect differences in the ceramide content of cellular membranes. KW - liposome KW - ceramide KW - cell membrane model Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-286130 SN - 2079-4983 VL - 13 IS - 3 ER - TY - JOUR A1 - Brachner, Andreas A1 - Fragouli, Despina A1 - Duarte, Iola F. A1 - Farias, Patricia M. A. A1 - Dembski, Sofia A1 - Ghosh, Manosij A1 - Barisic, Ivan A1 - Zdzieblo, Daniela A1 - Vanoirbeek, Jeroen A1 - Schwabl, Philipp A1 - Neuhaus, Winfried T1 - Assessment of human health risks posed by nano-and microplastics is currently not feasible JF - International Journal of Environmental Research and Public Health N2 - The exposure of humans to nano-and microplastic particles (NMPs) is an issue recognized as a potential health hazard by scientists, authorities, politics, non-governmental organizations and the general public. The concentration of NMPs in the environment is increasing concomitantly with global plastic production and the usage of plastic materials. NMPs are detectable in numerous aquatic organisms and also in human samples, therefore necessitating a risk assessment of NMPs for human health. So far, a comprehensive risk assessment of NMPs is hampered by limited availability of appropriate reference materials, analytical obstacles and a lack of definitions and standardized study designs. Most studies conducted so far used polystyrene (PS) spheres as a matter of availability, although this polymer type accounts for only about 7% of total plastic production. Differently sized particles, different concentration and incubation times, and various biological models have been used, yielding hardly comparable data sets. Crucial physico-chemical properties of NMPs such as surface (charge, polarity, chemical reactivity), supplemented additives and adsorbed chemicals have been widely excluded from studies, although in particular the surface of NMPs determines the interaction with cellular membranes. In this manuscript we give an overview about the critical parameters which should be considered when performing risk assessments of NMPs, including novel reference materials, taking into account surface modifications (e.g., reflecting weathering processes), and the possible role of NMPs as a substrate and/or carrier for (pathogenic) microbes. Moreover, we make suggestions for biological model systems to evaluate immediate toxicity, long-term effects and the potential of NMPs to cross biological barriers. We are convinced that standardized reference materials and experimental parameters along with technical innovations in (nano)-particle sampling and analytics are a prerequisite for the successful realization of conclusive human health risk assessments of NMPs. KW - nanoplastics KW - nanoparticles KW - microplastics KW - microparticles KW - human exposure KW - biological barriers KW - biofilm KW - microbe carrier KW - toxicity KW - neurotoxicity Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-219423 SN - 1660-4601 VL - 17 IS - 23 ER - TY - JOUR A1 - Scherzad, Agmal A1 - Meyer, Till A1 - Ickrath, Pascal A1 - Gehrke, Thomas Eckhart A1 - Bregenzer, Maximillian A1 - Hagen, Rudolf A1 - Dembski, Sofia A1 - Hackenberg, Stephan T1 - Cultivation of hMSCs in human plasma prevents the cytotoxic and genotoxic potential of ZnO-NP in vitro JF - Applied Sciences N2 - Zinc oxide nanoparticles (ZnO-NPs) are commonly used for industrial applications. Consequently, there is increasing exposure of humans to them. The in vitro analysis of cytotoxicity and genotoxicity is commonly performed under standard cell culture conditions. Thus, the question arises of how the results of genotoxicity and cytotoxicity experiments would alter if human plasma was used instead of cell culture medium containing of fetal calf serum (FCS). Human mesenchymal stem cells (hMSCs) were cultured in human plasma and exposed to ZnO-NPs. A cultivation in expansion medium made of DMEM consisting 10% FCS (DMEM-EM) served as control. Genotoxic and cytotoxic effects were evaluated with the comet and MTT assay, respectively. hMSC differentiation capacity and ZnO-NP disposition were evaluated by histology and transmission electron microscopy (TEM). The protein concentration and the amount of soluble Zn2+ were measured. The cultivation of hMSCs in plasma leads to an attenuation of genotoxic and cytotoxic effects of ZnO-NPs compared to control. The differentiation capacity of hMSCs was not altered. The TEM showed ZnO-NP persistence in cytoplasm in both groups. The concentrations of protein and Zn2+ were higher in plasma than in DMEM-EM. In conclusion, the cultivation of hMSCs in plasma compared to DMEM-EM leads to an attenuation of cytotoxicity and genotoxicity in vitro. KW - ZnO-NP KW - mesenchymal stem cells KW - genotoxicity KW - cytotoxicity KW - human plasma Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-193063 SN - 2076-3417 VL - 9 IS - 23 ER - TY - JOUR A1 - Meyer, Till Jasper A1 - Scherzad, Agmal A1 - Moratin, Helena A1 - Gehrke, Thomas Eckert A1 - Killisperger, Julian A1 - Hagen, Rudolf A1 - Wohlleben, Gisela A1 - Polat, Bülent A1 - Dembski, Sofia A1 - Kleinsasser, Norbert A1 - Hackenberg, Stephan T1 - The radiosensitizing effect of zinc oxide nanoparticles in sub-cytotoxic dosing is associated with oxidative stress in vitro JF - Materials N2 - Radioresistance is an important cause of head and neck cancer therapy failure. Zinc oxide nanoparticles (ZnO-NP) mediate tumor-selective toxic effects. The aim of this study was to evaluate the potential for radiosensitization of ZnO-NP. The dose-dependent cytotoxicity of ZnO-NP\(_{20 nm}\) and ZnO-NP\(_{100 nm}\) was investigated in FaDu and primary fibroblasts (FB) by an MTT assay. The clonogenic survival assay was used to evaluate the effects of ZnO-NP alone and in combination with irradiation on FB and FaDu. A formamidopyrimidine-DNA glycosylase (FPG)-modified single-cell microgel electrophoresis (comet) assay was applied to detect oxidative DNA damage in FB as a function of ZnO-NP and irradiation exposure. A significantly increased cytotoxicity after FaDu exposure to ZnO-NP\(_{20 nm}\) or ZnO-NP\(_{100 nm}\) was observed in a concentration of 10 µg/mL or 1 µg/mL respectively in 30 µg/mL of ZnO-NP\(_{20 nm}\) or 20 µg/mL of ZnO-NP\(_{100 nm}\) in FB. The addition of 1, 5, or 10 µg/mL ZnO-NP\(_{20 nm}\) or ZnO-NP\(_{100 nm}\) significantly reduced the clonogenic survival of FaDu after irradiation. The sub-cytotoxic dosage of ZnO-NP\(_{100 nm}\) increased the oxidative DNA damage compared to the irradiated control. This effect was not significant for ZnO-NP\(_{20 nm}\). ZnO-NP showed radiosensitizing properties in the sub-cytotoxic dosage. At least for the ZnO-NP\(_{100 nm}\), an increased level of oxidative stress is a possible mechanism of the radiosensitizing effect. KW - zinc oxide nanoparticles KW - irradiation KW - oxidative DNA damage KW - head and neck squamous cell carcinoma Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-193897 SN - 1996-1944 VL - 12 IS - 24 ER - TY - JOUR A1 - Straßer, Marion A1 - Schrauth, Joachim H. X. A1 - Dembski, Sofia A1 - Haddad, Daniel A1 - Ahrens, Bernd A1 - Schweizer, Stefan A1 - Christ, Bastian A1 - Cubukova, Alevtina A1 - Metzger, Marco A1 - Walles, Heike A1 - Jakob, Peter M. A1 - Sextl, Gerhard T1 - Calcium fluoride based multifunctional nanoparticles for multimodal imaging JF - Beilstein Journal of Nanotechnology N2 - New multifunctional nanoparticles (NPs) that can be used as contrast agents (CA) in different imaging techniques, such as photoluminescence (PL) microscopy and magnetic resonance imaging (MRI), open new possibilities for medical imaging, e.g., in the fields of diagnostics or tissue characterization in regenerative medicine. The focus of this study is on the synthesis and characterization of CaF\(_{2}\):(Tb\(^{3+}\),Gd\(^{3+}\)) NPs. Fabricated in a wet-chemical procedure, the spherical NPs with a diameter of 5–10 nm show a crystalline structure. Simultaneous doping of the NPs with different lanthanide ions, leading to paramagnetism and fluorescence, makes them suitable for MR and PL imaging. Owing to the Gd\(^{3+}\) ions on the surface, the NPs reduce the MR T\(_{1}\) relaxation time constant as a function of their concentration. Thus, the NPs can be used as a MRI CA with a mean relaxivity of about r = 0.471 mL·mg\(^{−1}\)·s\(^{−1}\). Repeated MRI examinations of four different batches prove the reproducibility of the NP synthesis and determine the long-term stability of the CAs. No cytotoxicity of NP concentrations between 0.5 and 1 mg·mL\(^{−1}\) was observed after exposure to human dermal fibroblasts over 24 h. Overall this study shows, that the CaF\(_{2}\):(Tb\(^{3+}\),Gd\(^{3+}\)) NPs are suitable for medical imaging. KW - calcium fluoride nanoparticles KW - magnetic resonance imaging (MRI) KW - multifunctional nanoparticles KW - multimodal imaging KW - photoluminescence Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-170657 VL - 8 ER -