3D Cell Printing of Brain Blood Vessels to Investigate Metastatic Cancer Development Related to Vascular Geometry

Abstract

Cerebral vessels are complexly structured for supporting efficient blood perfusion to meet the high metabolic energy demand of brain. This geometric complexity alters hemodynamic flow patterns, affecting the transport of circulating tumor cells and contributing to brain metastasis. Yet, biomimetic engineering technology enabling to investigate the correlation of metastatic cancer development with vascular structure has been underexplored. In this study, we created functional cerebrovascular conduits in vitro, employing an in-bath 3D multiaxial cell printing strategy and a brain extracellular matrix- based bioink. The multilayered cellular constructs with varying curvatures discern underlying biomechanical and biological mechanisms during cancer metastasis that the blood vessels with larger bends may generate regions with low blood flow velocity and wall shear stress, prolong tumor residence time to contact more tumor cells, and accelerate sequential metastatic cascades. The development represents a significant milestone in advancing the field of metastatic cancer modeling and hold promise for future breakthroughs in pharmaceutical and medical advancements.