Vascular architecture-on-chip: engineering complex blood vessels for reproducing physiological and heterogeneous hemodynamics and endothelial function.

Human circulation exhibits significant diversity and heterogeneity of blood vessel shapes. The complex architecture of these vessels may be physiological or pathological resulting in unique hemodynamics and endothelial cell phenotypes that may determine the regulation and alteration of cell signaling pathways and vascular function. While human microphysiological systems of blood vessels (vessel-chips) have mimicked several aspects of vascular pathophysiology, engineering of these tools is still limited to the fabrication of homogeneous tubular structures, especially when living endothelial cell culture is also included. Here, a common unifying approach based on gravitational lumen patterning (GLP) is presented to create non-uniform, living 3D and closed vascular lumens embedded in a collagen matrix and lined with endothelial cells, resulting in reproduction of the architecture of straight vessels, stenosis, bifurcations, aneurysms and tortuous vessels. Upon blood perfusion, these systems reveal the nature of altered flow dynamics and corresponding endothelial cell morphology. These vessel-chips closely mimic the structural variations and resulting endothelial responses often observed and may be used to investigate vascular complications like aortic and cerebral aneurysm, arterial tortuosity syndrome, atherosclerosis, carotid artery disease, , where architecture plays a crucial role in disease onset and progression.