Date of Award

8-2018

Document Type

Thesis

Degree Name

Master of Science (MS)

Department

Bioengineering

Committee Member

Dr. Delphine Dean, Committee Chair

Committee Member

Dr. Bruce Gao

Committee Member

Dr. William Richardson

Abstract

Vascular smooth muscle cells regulate blood flow by contracting and relaxing blood vessels. Vascular smooth muscle cells display one of two distinct phenotypes: contractile or synthetic. The contractile phenotype enables cells to contract, and the majority of cells in healthy blood vessels exhibit this phenotype. Transition to the synthetic phenotype is associated with abnormal mechanical forces and the development of vascular diseases, including hypertension and atherosclerosis. Cell-extracellular matrix interactions and mechanical stimulation are factors that affect phenotypic modulation. Micropatterning techniques create a microenvironment used to control cell morphology, adhesion, migration, proliferation, and differentiation. Vascular smooth muscle cells are circumferentially arranged in blood vessels, so parallel cell alignment mimics the native environment. Micropatterning vascular smooth muscle cells, either onto topographical features or extracellular matrix protein patterns, has been shown to promote a more contractile, in vivo-like phenotype. Vascular smooth muscle cells are exposed to continuous mechanical signaling from pulsatile blood flow, which enforces the contractile phenotype. Applying a physiologically relevant, cyclic stretching regimen to vascular smooth muscle cells also promotes contractile functioning. The purpose of this study was to determine the effects of micropatterning and mechanical stimulation on vascular smooth muscle cell phenotype. Three micropatterning techniques were implemented to determine the best method for aligning vascular smooth muscle cells. Microstamping was effective at patterning collagen but did not promote sufficient cell alignment. Stencil patterning vascular smooth muscle cells on a collagen layer was found to promote cell alignment with minimal cell spreading. Stenciled cells were exposed to physiological cyclic stretch using the MechanoCulture FX mechanical stimulation system (CellScale). The combination of stencil patterning and stretching reduced cell proliferation and promoted a more contractile phenotype.

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