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DC Field | Value | Language |
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dc.contributor.advisor | Selvaganapathy, Ponnambalam | - |
dc.contributor.author | Jalali, Seyedaydin | - |
dc.date.accessioned | 2024-08-23T15:43:30Z | - |
dc.date.available | 2024-08-23T15:43:30Z | - |
dc.date.issued | 2024 | - |
dc.identifier.uri | http://hdl.handle.net/11375/30072 | - |
dc.description.abstract | Tissue barriers protect the body from external pathogens and maintain homeostasis by regulating nutrient and gas transport. Dysfunction in these barriers can cause serious diseases, emphasizing the need for accurate models for therapy development. While animal models provide useful data, they have ethical, cost, and physiological limitations. Human ex vivo models are limited by ethical concerns, tissue availability, and variability. In vitro models have emerged as a solution; however, current models often oversimplify and fail to replicate critical cellular behaviors and interactions under various conditions. Modeling tissue barriers in vitro is particularly challenging due to the need for highly confluent cellular barriers within multi-compartment setups to enable realistic transport studies. This is especially complex for structures like the placenta, which features multiple layers and cell types and undergoes rapid developmental changes. The objective of this doctoral thesis was to develop a biofabrication technique using the self-assembly method to create in vitro tissue barrier models that mirror the permeability traits found in vivo. We refined the self-assembly parameters and designed a polydimethylsiloxane (PDMS) device to construct 3D tubular, membrane-like tissues suitable for advanced transport studies. Our model successfully established continuous, highly confluent endothelial barriers through self-assembly and cellular migration. Next, using BeWo cells, a choriocarcinoma cell line, we mimicked the multilayer structure of the trophoblast layers in the placenta. We then facilitated the co-culture of endothelial cells and BeWo cells within a single, heterogeneous 3D tubular construct. This setup replicated the multilayer and multi-cell type structure of the placental barrier, with appropriate cell-ECM interactions. In summary, the fabrication techniques developed in this study enable the creation of in vitro tissue barrier models that closely represent the intricate architecture of tissue barriers, offering a physiologically relevant platform for detailed transport studies and maintaining high cellular confluency and barrier integrity. | en_US |
dc.language.iso | en | en_US |
dc.title | Development of Biofabrication Techniques to Engineer 3D in vitro Models of Tissue Barriers | en_US |
dc.type | Thesis | en_US |
dc.contributor.department | Biomedical Engineering | en_US |
dc.description.degreetype | Thesis | en_US |
dc.description.degree | Doctor of Philosophy (PhD) | en_US |
dc.description.layabstract | This doctoral thesis focuses on developing new ways to create laboratory models of tissue barriers, such as the placenta, that closely mimic the complex structures of these barriers in the human body. Tissue barriers are crucial for protecting the body from external pathogens and regulating the transport of nutrients and gases. However, creating accurate models to study these barriers has been challenging due to ethical concerns with animal models and the limitations of human tissue samples. To overcome these challenges, this research employed a method called self-assembly to build three-dimensional models that simulate the detailed architecture of natural tissue barriers. The models successfully replicated the layered structure of the placenta using a combination of endothelial cells, which line blood vessels, and BeWo cells, a type of cell that mimics placental cells. Overall, the techniques developed in this study provide a sophisticated and physiologically relevant platform that could enhance our understanding of tissue barriers and support the development of new therapeutic approaches. These models offer a promising tool for research into the mechanisms by which substances are transported across these critical barriers. | en_US |
Appears in Collections: | Open Access Dissertations and Theses |
Files in This Item:
File | Description | Size | Format | |
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Jalali_Seyedaydin_202408_PhD.pdf | 5.85 MB | Adobe PDF | View/Open |
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