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Title: Cell response to physical stimuli in dynamic culture
Author: Brown, Stephen Alan
Awarding Body: University of Ulster
Current Institution: Ulster University
Date of Award: 2012
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Endothelial cells are known to respond directly to their physical environment, with morphological changes in response to fluid shear stress being associated with a number of key cellular functions and disease processes such as angiogenesis, cell migration and atherosclerosis. Alignment and elongation of endothelial cells can result from culturing them on substrates with specific micro-features. If simple, cost-effective physical cues can be used to direct endothelial cell function, significant advances could be made in a number of fields, including Tissue Engineering and Regenerative Medicine (TERM), vascular biomaterials and drug development. This research considers two distinct forms of physical stimuli of endothelial cells, namely Laminar Shear Stress (LSS) and hot embossed surface micro-features, created on Tissue Culture Treated Polystyrene (TCPS). Using both experimental and computational methods the nature of the effects of these forms of stimuli have been investigated separately and in combination. The resulting information enables a number of key experimental outcomes to be presented. Firstly, while hot embossing is able to produce consistent and repeatable micro-scale features, it has a subtle but significant effect on the TCPS surface, changing both surface chemistry and roughness in a manner that can result in changes in cell adhesion and proliferation. Secondly, Bovine Aortic Endothelial Cells (BAECs) align and elongate in response to culture on hot embossed ridge features and to LSS stimulus, with notable cytoskeletal differences observed between cells aligned as a result of the different forms of stimuli. Application of these stimuli in combination suggests that the nature of the cell adhesion to the substrate is a key factor in determining the response to LSS. Thirdly, the specific topography of an adhered endothelial monolayer changes the resulting shear stress and so must be considered if the responses to LSS are to be correctly understood. Computational Fluid Dynamics (CFD) modelling has determined that spatial gradients of the shear stress may be more important than its magnitude when considering the adhesion of endothelial cells. Finally, it has been observed that a combination of specific surface chemistry, roughness and micro-features is able to promote a pronounced form of directional tubule formation in BAECs.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available