Date of Graduation
Statler College of Engineering and Mineral Resources
Chemical and Biomedical Engineering
Cells are typically housed in a complex microenvironment (ECM) in vivo, where the cells interact with the extracellular matrix (ECM) and neighboring cells. The ECM provides physical support for cells and affects cell adhesion, migration, proliferation, differentiation, and gene expression. Primary components of the ECM include fibrous proteins which contribute significant nanotopography cues to cells. Due to limitations of two-dimensional (2-D) in vitro studies where cells are cultured on flat, plastic substrates, the conventional cell culture does not mimic the in vivo scenario. This manifests the critical need for biomimetic cell culture platforms which mimic the in vivo microenvironment. During my graduate studies, two in vitro disease models were constructed to investigate cell-substrate and cell-cell interactions.;In Chapter I, nanotopographical effects on cell responses were examined. Focal adhesions and nuclear deformation of normal human lung fibroblasts (NHLFs) were investigated. In general, nanoscale gratings hindered cell spreading and thus reduced cell size while increasing the nuclear volume. On the other hand, nanoscale pillars, depending on the feature size and spacing, might modulate the focal adhesions and nuclear size towards opposite directions. Our observations suggested that it was focal adhesion area instead of focal adhesion size that affected nuclear deformation. Therefore, nanotopography could be optimized to modulate cell adhesion and nuclear volume, which would provide a useful tool to regulate cell phenotypes and functions for end applications.;In Chapter II, the effects of cell-cell and cell-matrix interactions on tumor cell survival within an engineered bone marrow microenvironment for Acute Lymphoblastic Leukemia (ALL) were evaluated. In this study, biologically relevant populations of primary human derived bone marrow stromal cells (BMSCs), osteoblasts and a human ALL cell line representative of an aggressive phenotype were used. Traditional 2-D co-culture, 3-D static culture in collagen, and 3-D cultures with flow were evaluated to determine response to a commonly used chemotherapeutic agent, Ara-C. 3-D co-culture models showed higher survival of tumor cells during Ara-C exposure as well as enhanced protection during chemotherapy stress conferred by microenvironment cells.
Bruce, Allison, "Creation of in vitro disease models using micro-nanoengineering" (2014). Graduate Theses, Dissertations, and Problem Reports. 7303.