Vascular diseases, such as atherosclerosis and thrombosis, are the leading cause of morbidity and mortality worldwide. Despite major advancements to develop therapeutic interventions, the pathophysiology as it applies to humans is largely unclear and treatments limited. Thus, there is a critical need to increase our understanding of vascular physiology and assess emerging interventions in order to accelerate therapeutic development. Here, we designed a three-dimensional (3D) bioprinted vascular tissue platform that recapitulates both the multicellular constituents and tissue architecture innate to human vessels. Specifically, we introduced a new class of nanoengineered, hydrogel-based bioinks to fabricate anatomically accurate (10 mm diameter, 1 cm long), multicellular vessels with high printability, structural stability, and cytocompatibility. This approach permits for long-term co-culture of vascular smooth muscle cells (VSMCs) and endothelial cells (ECs), providing the opportunity to model vessel function and pathophysiology. To validate the ability of this platform to accurately reflect and model the onset of vascular thromboinflammation, 3D printed vessels were treated with the cytokine tumor necrosis factor-? (TNF-?), disrupting vascular EC barrier function. In the presence of a confluent lumen without TNF-? stimulation, no clotting was observed upon blood perfusion. However, in cytokine-treated vessels, a dose-dependent response in clotting formation was observed. Furthermore, a significantly altered clotting phenomena was observed in EC-VSMC co-cultures relative to independent cell culture, suggesting cellular cross-talk and communication within the 3D printed model. Overall, these studies demonstrate the ability of 3D bioprinted vessels to recapitulate human in vivo pathophysiology, thus illustrating the essential coupling between biology, engineering, and material science, impacting preclinical research studies.
