Interactions between blood and the vessel wall control the homeostasis in normal physiology, and when disturbed, it may initiate many disease processes. The Zheng lab has developed chips with artificial vessels with appropriate geometries and human-only components to understand the initiation and progression of thrombosis and organ-specific diseases. We have studied initial events of thrombosis during acute inflammation, including when von Willebrand factor is secreted from the vessel wall, initiating the platelet adhesion and thrombosis, as one mechanism of thrombotic microangiopathies. These models allow us to develop a human organ specific vascular bed lined with appropriate microvascular cells and simulate the 3D organization and size of vessels in vivo.

Blood vessels grow through three distinct processes: vasculogenesis, angiogenesis, and arteriogenesis. These terms describe, respectively, de novo growth of new blood vessels, growth of new vessels from preexisting ones, and increases in the size of preexisting vessels. Much attention has been devoted to sprouting angiogenesis and genetic mechanisms underlying cardiovascular development. However, little is known about the factors that govern vascular remodeling - the dynamic modification of existing vascular structure, particularly as a function of circulating blood flow and vascular wall components. Our interest is to build in vitro vascular models to control vascular structure. We have so far successfully generated prepatterned vessels with self-assembled vasculature individually, and we are developing approaches to combine them and drive them to remodel with proper hydrodynamic flow and pressure. The success of the control for vascular remodeling in vitro will revolutionize the tools for the study of vascular cell biology and tissue scale biology. 

The endothelium first forms in the blood islands in the extra-embryonic yolk sac and then throughout the embryo to establish circulatory networks that further acquire organ-specific properties during development to support diverse organ functions. It has been challenging to understand these heterogeneities for human vasculature. Our goal is to understand organ-specific endothelial cell heterogeneity from primary cells isolated from human organs, develop cell lines. We aim to understand their unique structure and functions to support the organ development. Furthermore, we are also working towards control of differentiation of endothelial cells from human pluripotent stem cells, towards organ-specific properties.

Engineered tissues hold promise to 1) develop tissue or organ substitutes for clinical transplantation to replace damaged regions and restore organ function, and 2) to build human tissue chips and replace animal models for drug screening and disease modeling. However, each organ varies in its unique structural components – different cell types, matrix and architecture, biophysical environment – pressure and flow, and biochemical stimuli – oxygen tension, cytokines and growth factors, to support specific organ functions. Our goal is to build organ-specific vascular niche to model vascular injuries and diseases.