3D bioprinted multilayered cerebrovascular conduits to study cancer extravasation mechanism related with vascular geometry

Wonbin Park, Jae-Seong Lee, Ge Gao, Byoung Soo Kim () and Dong-Woo Cho ()
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Wonbin Park: Pohang University of Science and Technology
Jae-Seong Lee: Pusan National University
Ge Gao: Beijing Institute of Technology
Byoung Soo Kim: Pusan National University
Dong-Woo Cho: Pohang University of Science and Technology

Nature Communications, 2023, vol. 14, issue 1, 1-14

Abstract: Abstract Cerebral vessels are composed of highly complex structures that facilitate blood perfusion necessary for meeting the high energy demands of the brain. Their geometrical complexities alter the biophysical behavior of circulating tumor cells in the brain, thereby influencing brain metastasis. However, recapitulation of the native cerebrovascular microenvironment that shows continuities between vascular geometry and metastatic cancer development has not been accomplished. Here, we apply an in-bath 3D triaxial bioprinting technique and a brain-specific hybrid bioink containing an ionically crosslinkable hydrogel to generate a mature three-layered cerebrovascular conduit with varying curvatures to investigate the physical and molecular mechanisms of cancer extravasation in vitro. We show that more tumor cells adhere at larger vascular curvature regions, suggesting that prolongation of tumor residence time under low velocity and wall shear stress accelerates the molecular signatures of metastatic potential, including endothelial barrier disruption, epithelial–mesenchymal transition, inflammatory response, and tumorigenesis. These findings provide insights into the underlying mechanisms driving brain metastases and facilitate future advances in pharmaceutical and medical research.

Date: 2023
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DOI: 10.1038/s41467-023-43586-4

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