Year of Publication

2016

Degree Name

Master of Science in Biomedical Engineering

Document Type

Master's Thesis

College

Engineering

Department

Biomedical Engineering

First Advisor

Dr. Hainsworth Shin

Abstract

This study explored hydrostatic pressure as a mechanobiological parameter to control in vitro endothelial cell tubulogenesis in 3-D hydrogels as a model microvascular tissue engineering approach. For this purpose, the present investigation used an endothelial spheroid model, which we believe is an adaptable microvascularization strategy for many tissue engineering construct designs. We also aimed to identify the operating magnitudes and exposure times for hydrostatic pressure-sensitive sprout formation as well as verify the involvement of VEGFR-3 signaling. For this purpose, we used a custom-designed pressure system and a 3-D endothelial cell spheroid model of sprouting tubulogenesis. We report that an exposure time of 3 days is the minimum duration required to increase endothelial sprout formation in response to 20 mmHg. Notably, exposure to 5 mmHg for 3 days was inhibitory for endothelial spheroid lengths without affecting sprout numbers. Moreover, endothelial spheroids exposed to 40 mmHg also inhibited sprouting activity by reducing sprout numbers without affecting sprout lengths. Finally, blockade of VEGFR-3 signaling abolished the effects of the 20-mmHg stimuli on sprout formation. Based on these results, VEGFR-3 dependent endothelial sprouting appears to exhibit a complex pressure dependence that one may exploit to control microvessel formation.

Digital Object Identifier (DOI)

http://dx.doi.org/10.13023/ETD.2016.164

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