Xiang Li

Date of Graduation

2014

Document Type

Dissertation

Degree Type

PhD

College

Statler College of Engineering and Mineral Resources

Department

Chemical and Biomedical Engineering

Committee Chair

Yuxin Liu

Committee Co-Chair

Thirimachos Bourlai

Committee Member

Jeremy Dawson

Committee Member

Pingnian He

Committee Member

Larry A Hornak

Committee Member

Nianqiang Wu

Abstract

Microfluidic technologies have enabled in vitro studies to mimic in vivo microvessel environment with sufficient complexity. However, there are still existing knowledge gaps and lack of convincing evidence to demonstrate and quantify key features of a functional microvessel. In this dissertation, a physiologically realistic microvessel model was developed with a stable and mature endothelium for studying complex vascular phenomena, such as endothelial cell signaling and barrier functions with the microscopic resolution at individual cellular levels. With advanced micromanufacturing and microfluidic technologies, two types of cost-efficient, easy to operate and reproducible microchannel network devices were fabricated, and the fabricated microchannels mimicked the dimension of in vivo microvessels. With long-term and continuous perfusion control, seeded endothelial cells were able to maintain their phenotype, viability, proliferation with proper barrier functions, and respond to flow shear force and inflammatory stimuli. In particular, primary human umbilical vein endothelial cells were successfully cultured the entire inner surface of the microchannel network with well-developed VE-cadherin junctions throughout the channels. The endothelial cell response to shear stresses were quantified under different shear stress conditions and demonstrated their morphological changes close to those reported in venular vasculature. Furthermore, real time agonist-induced changes in intracellular Ca2+ concentration [Ca2+]i and nitric oxide (NO) production was successfully measured by integrating microvessel model into microscopic systems. The results were similar and comparable to those derived from individually perfused intact venules. With the validation of its functionalities, this microfluidic model demonstrates a great potential for biological applications and bridging the gaps between in vitro and in vivo microvascular research.

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