Title: Microtechnologies for Cardiovascular Tissue Engineering
Description: Cardiovascular disease is a rising epidemic worldwide, and curative therapies remain elusive. Heart and vascular disease remain some of the hardest to cure due to the limited capacity of the heart to repair itself, necessitating a cell or organ based therapy to cure the inevitable descent into heart failure. Tissue engineering is uniquely poised to significantly alter this disease burden though the fabrication of cardiac and vascular tissues in vitro. However, the challenges for achieving these aims are significant - for cardiac tissues, the therapy must adhere to strict requirements of adequate perfusion and functional integration with the damaged heart. Vascular tissues are required to be amenable to surgical anastomosis while at the same time provide nutrient transport on the cellular level. Recently, a new set of technologies based from the semiconductor industry, have enabled micron level control over the cellular environment and cells themselves and may enable novel approaches to fulfill these tissue engineering requirements.

In this dissertation, these microtechnologies will be leveraged to address some of the current obstacles that limit the use of tissue engineering approaches for functional therapy. Specifically, microtechnologies were used to screen the effect of electrical stimulation on the function and maturation of human embryonic stem cell derived cardiomyocytes, which resulted in the ability to program specific individual beating frequencies of the cells while improving contractile function and led to the identification of a channel specific effect for frequency modulation. These technologies were also used to distinguish the vasculogenic potential of different mesenchymal stem cell sources for nascent vessel stabilization, and enabled the development of a powerful hydrogel docking platform with the novel capability to spatially pattern any number of cells, cytokines or drugs on the microscale, while permitting scale up for larger tissue generation without the loss of precision. Finally, these technologies were used to create vascular networks with hierarchical branching patterns that could be implanted and used in vivo fulfilling a major criterion of vascular tissue function - surgical compatibility with microscale architecture for tissue perfusion.

Therefore, these microtechnologies support novel interrogation of cell function and enable new methods to engineer cardiovascular tissues.