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Nat. Commun., Nov 24 2023, 14 (1) | https://doi.org/10.1038/s41467-023-43586-4 3D bioprinted multilayered cerebrovascular conduits to study cancer extravasation mechanism related with vascular geometry

Wonbin Park ¹, Jae-Seong Lee ², Ge Gao ³, Byoung Soo Kim ^2,4,* & Dong-Woo Cho ^1,*

¹Department of Mechanical Engineering, Pohang University of Science and Technology, Pohang, Republic of Korea.
²School of Biomedical Convergence Engineering, Pusan National University, Yangsan, Republic of Korea.
³School of Medical Technology, Beijing Institute of Technology, Beijing, China.
⁴Medical Research Institute, Pusan National University, Yangsan, Republic of Korea.

^*Corresponding authors: correspondence to Byoung Soo Kim or Dong-Woo Cho

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.

논문정보

형식Research article
게재일2023년 11월 (BRIC 등록일 2023-11-27)
연구진국내(교신)+국외 연구진
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