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

Author

Listed:
  • 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
    Pusan National University)

  • Dong-Woo Cho

    (Pohang University of Science and Technology)

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.

Suggested Citation

  • Wonbin Park & Jae-Seong Lee & Ge Gao & Byoung Soo Kim & Dong-Woo Cho, 2023. "3D bioprinted multilayered cerebrovascular conduits to study cancer extravasation mechanism related with vascular geometry," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
  • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-43586-4
    DOI: 10.1038/s41467-023-43586-4
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    1. Paula D. Bos & Xiang H.-F. Zhang & Cristina Nadal & Weiping Shu & Roger R. Gomis & Don X. Nguyen & Andy J. Minn & Marc J. van de Vijver & William L. Gerald & John A. Foekens & Joan Massagué, 2009. "Genes that mediate breast cancer metastasis to the brain," Nature, Nature, vol. 459(7249), pages 1005-1009, June.
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