3D bioprinted multilayered cerebrovascular conduits to study cancer extravasation mechanism related with vascular geometry
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....
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2023-11-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-023-43586-4 |
| _version_ | 1827633777667473408 |
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| author | Wonbin Park Jae-Seong Lee Ge Gao Byoung Soo Kim Dong-Woo Cho |
| author_facet | Wonbin Park Jae-Seong Lee Ge Gao Byoung Soo Kim Dong-Woo Cho |
| author_sort | Wonbin Park |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-09T15:04:15Z |
| format | Article |
| id | doaj.art-b50aeadcc8a04df8b7c341c28a0efedd |
| institution | Directory Open Access Journal |
| issn | 2041-1723 |
| language | English |
| last_indexed | 2024-03-09T15:04:15Z |
| publishDate | 2023-11-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj.art-b50aeadcc8a04df8b7c341c28a0efedd2023-11-26T13:45:39ZengNature PortfolioNature Communications2041-17232023-11-0114111410.1038/s41467-023-43586-43D bioprinted multilayered cerebrovascular conduits to study cancer extravasation mechanism related with vascular geometryWonbin Park0Jae-Seong Lee1Ge Gao2Byoung Soo Kim3Dong-Woo Cho4Department of Mechanical Engineering, Pohang University of Science and TechnologySchool of Biomedical Convergence Engineering, Pusan National UniversitySchool of Medical Technology, Beijing Institute of TechnologySchool of Biomedical Convergence Engineering, Pusan National UniversityDepartment of Mechanical Engineering, Pohang University of Science and TechnologyAbstract 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.https://doi.org/10.1038/s41467-023-43586-4 |
| spellingShingle | Wonbin Park Jae-Seong Lee Ge Gao Byoung Soo Kim Dong-Woo Cho 3D bioprinted multilayered cerebrovascular conduits to study cancer extravasation mechanism related with vascular geometry Nature Communications |
| title | 3D bioprinted multilayered cerebrovascular conduits to study cancer extravasation mechanism related with vascular geometry |
| title_full | 3D bioprinted multilayered cerebrovascular conduits to study cancer extravasation mechanism related with vascular geometry |
| title_fullStr | 3D bioprinted multilayered cerebrovascular conduits to study cancer extravasation mechanism related with vascular geometry |
| title_full_unstemmed | 3D bioprinted multilayered cerebrovascular conduits to study cancer extravasation mechanism related with vascular geometry |
| title_short | 3D bioprinted multilayered cerebrovascular conduits to study cancer extravasation mechanism related with vascular geometry |
| title_sort | 3d bioprinted multilayered cerebrovascular conduits to study cancer extravasation mechanism related with vascular geometry |
| url | https://doi.org/10.1038/s41467-023-43586-4 |
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