Engineered, perfusable, human microvascular networks on a microfluidic chip

Abstract

In this thesis, we developed a reliable platform for engineering perfusable, microvascular networks on-demand using state of the art microfluidics technology. We have demonstrated the utility of this platform for studying cancer metastasis and as a test bed for drug discovery and analysis. In parallel, this platform enabled us to study, in a highly controlled environment, the physiologic processes of angiogenesis and vasculogenesis to further elucidate their underlying mechanisms. In addition to using our platform for real-time observation of physiological processes, we also took advantage of the ability to influence these processes through precise control of the extracellular environment. By manipulating the mechanical and bio-chemical inputs to our system, we controlled the dynamics of microvascular network formation as well as key properties of the network morphology. These findings will aid in the design and engineering of organ specific constructs for tissue engineering and regenerative medicine applications. Finally, we explored the potential use of stem cells for engineering microvascular networks in our system. We found that human mesenchymal stem cells can act as secondary, support cells during microvascular network formation.