Objectives To develop an in vitro model for studying the biological effect of complex-flow stress on endothelial cells in three-dimensional (3D) patient-specific vascular geometry.
Materials and methods A vessel replica was fabricated with polydimethylsiloxanes using 3D printing technology from vascular image data acquired by rotational angiography. The vascular model was coated with fibronectin and immersed in a tube filled with a cell suspension of endothelium, and then cultured while being slowly rotated in three dimensions. Culture medium with viscosity was perfused in the circulation with the endothelialized vascular model. A computational fluid dynamics (CFD) study was conducted using perfusion conditions used in the flow experiment. The morphology of endothelial cells was observed under a confocal microscope.
Results The CFD study showed low wall shear stress and circulating flow in the apex of the basilar tip aneurysm, with linear flow in the parent artery. Confocal imaging demonstrated that the inner surface of the vascular model was evenly covered with monolayer endothelial cells. After 24 h of flow circulation, endothelial cells in the parent artery exhibited a spindle shape and aligned with the flow direction. In contrast, endothelial cells in the aneurysmal apex were irregular in shape and size.
Conclusions A geometrically realistic intracranial aneurysm model with live endothelial lining was successfully developed. This in vitro model enables a new research approach combining study of the biological impact of complex flow on endothelial cells with CFD analysis and patient information, including the presence of aneurysmal growth or rupture.
- blood flow
- vessel wall
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Contributors NK: concept, design and development of the study, acquisition and analysis of the data, writing of the article. TM, EW: development of the study. KN: acquisition of the data. ST, KK: critical review of the article.
Funding KAKENHI (Grants-in Aid for Scientific Research) from Japan Society for the Promotion of Science (JSPS), grant no. 15K19978 to NK and Jichi Medical University Young Investigator Award, 2015 to NK.
Competing interests None declared.
Patient consent The study, including use of patient image data, was approved by the institutional review board, which waived the requirement for patients’ informed consent.
Ethics approval Institutional review board.
Provenance and peer review Not commissioned; externally peer reviewed.
Data sharing statement Any technical detail concerning the creation of the model and the results are available from the corresponding author.