As the main precursor of arterial disorders, endothelial dysfunction preferentially occurs in regions of arteries prone to generate turbulent flow, particularly in branched regions of vasculatures. Although diverse diseased models have been engineered to investigate arterial pathology, a multiple-layered vascular model with branched geometries that can recapitulate critical physiological environments of human arteries, such as intercellular communications and local turbulent flows, still remains challenging. This study develops a sequentially suspended 3D bioprinting (SSB) strategy and a visible-light-curable decellularized extracellular matrix (dECM) (VCD) bioink to construct a biomimetic human arterial model with tunable geometries. The engineered multiple-layered arterial models with compartmentalized vascular cells can exhibit physiological functionality and pathological performance under defined physiological flows speculated by computational fluid dynamics simulation. Upon different configurations of the vascular models, the independent and synergetic effects of cellular crosstalk and abnormal hemodynamic on the initiation of endothelial dysfunction, a hallmark event of arterial disorder, were investigated. These results suggest that the arterial model constructed using the SSB strategy and the VCD bioinks is promising to establish diagnostic/analytic platforms for understanding the pathophysiology of human arterial disorders and relevant abnormalities, such as atherosclerosis, aneurysm, and ischemic diseases.
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