A microscale tissue modeling device (MTMD) to influence renal epithelial cell function through controlled topography and flow-induced shear stress
Frohlich, Else Marie
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Physiologically representative and well-controlled in vitro models of human tissue are required to safely, accurately, and rapidly develop therapies for disease. Current in vitro models do not possess appropriate levels of cell function, resulting in an inaccurate representation of in vivo physiology. Mechanical parameters, such as sub-micron substrate topography and flow-induced shear stress (FSS), can control cell functions such as alignment, migration, differentiation and phenotypic expression of cells[l, 2]. Combining, and independently controlling, topography and FSS in a cell culture device would provide a means to control cell function resulting in a more physiologically-representative in vitro model of human tissue. Here we develop the microscale tissue modeling device (MTMD) which couples an embossed topographical substrate with a molded microfluidic chamber to control both topography and FSS independently. As a model cell type, cells from the human renal proximal tubule cell line HK-2 were cultured in the MTMD and exposed to shear stress levels of 0.02 dyne/cm2 and 1.0 dyne/cm2 for two hours. Tests were conducted using both blank and topographical substrates, allowing the effects of FSS and surface topography to be studied independently and simultaneously. Results show that topography and FSS work in concert to elicit cell alignment and tight junction (TJ) formation, with topography enhancing and speeding cell response to FSS. The MTMD provides a more realistic in vitro model of human tissue by administering independently-controlled mechanical parameters to cell populations and shows great promise to enhance cell function studies, speed drug development, and provide a pathway to regenerative medicine therapies.
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