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dc.contributor.authorNalliah, Medhusja Sritharan
dc.date.accessioned2022-03-09T07:54:41Z
dc.date.issued2022-02-07
dc.date.submitted2022-03-08T23:00:22Z
dc.identifier.urihttps://hdl.handle.net/11250/2983876
dc.descriptionPostponed access: the file will be accessible after 2027-02-07
dc.description.abstractNanotechnology is a field of both research and innovation that is ever-growing. It Is the study and manipulation of matter at the nanoscale to produce materials and devices with enhanced properties. Industries are spending vast sums on developing nanotechnological prod-ucts with applicability in a wide range of fields, from electronics to medicines. The increas-ing use of nanotechnology in products raises an important question: what are the adverse effects of nanoparticles? There is a need for information about the possible toxic effects of engineered nanomaterials (NMs) and of nanoparticles (NPs). There is also a demand for re-liable methods, as the data and from existing literature on NPs’ adverse effects is contradic-tory, due to possible interferences of NPs with traditional toxicological methods. For a higher in vivo relevance, efforts are currently made to develop advanced in vitro biological meth-ods and instruments that resemble more closely real-life exposure. The purpose of this study was to assess the putative toxic effects of TiO2, CeO2 and Ag NPs, with different physio-chemical characteristics on endothelial cells, which are the cells that line the walls of blood vessels. Human endothelial cells were exposed to the NPs at different concentrations to evaluate the cytotoxicity of NPs by monitoring the cell viability and prolif-eration using label-free impedance-based monitoring (xCELLigence). In addition, the NPs ability to induce an increase in permeability of the endothelial barrier was evaluated. Lastly, optimization steps towards developing a microvasculature chip for measuring the effects of the same NPs in dynamic 3D model conditions were taken. The optimization consisted of finding the appropriate cell culturing protocol to obtain vasculogenesis in vitro. The results of the studies indicated that Ag nano-wires (AgNWs) were the most cytotoxic, followed by CeO2 10x10 nm. The AgNPs at 20 nm and 50 nm and TiO2 at 8 nm and 50 nm exhibited toxic traits at concentrations ≥50 µg/ml, and CeO2 50 nm showed adverse effects at concentrations 10-100 µg/ml. Ti nano-rods (TiNR) and CeO2 3.5 nm on the other hand showed low toxicity effects at tested concentrations (10, 50 and 100 µg/ml). All NPs also showed a concentration-dependent effect on the cell viability. As for size-dependent toxicity, only TiO2 NPs showed such an effect, while Ag and CeO2 did not. However, the cell viability assay revealed that the aspect ratio plays an essential role in NPs’ cytotoxicity. Based on the results from the permeability assay the tested NPs seemed to increase the permeability of endothelium, however possible NP-interference-based artifacts were observed. For vasculo-genesis optimization, a mixture of fibroblasts and HULEC-5a with the ratio of 1:2, respective-ly, in soft gels was preferred to form a capillary-like network. In conclusion, further investigation and optimization of the methods to test permeability are needed to draw definitive conclusions on the tested NP’s ability to increase permeability of an endothelium. The cell condition of one-part fibroblasts to two-parts HULEC-5a in soft-gel was sufficient to induce vasculogenesis, but not to form a complete capillary-like network as other factors (passage number, proliferation rate and gel stiffness) needs to be further examined
dc.language.isoeng
dc.publisherThe University of Bergen
dc.rightsCopyright the Author. All rights reserved
dc.subjectmicrofluidics
dc.subjectnanotoxicity
dc.titleDevelopment of Endothelial Barrier Models for Nanotoxicity Testing
dc.typeMaster thesis
dc.date.updated2022-03-08T23:00:22Z
dc.rights.holderCopyright the Author. All rights reserved
dc.description.degreeMasteroppgave i nanovitenskap
dc.description.localcodeNANO399
dc.description.localcodeMAMN-NANO
dc.subject.nus752902
fs.subjectcodeNANO399
fs.unitcode12-31-0
dc.date.embargoenddate2027-02-07


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