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具有内皮衬里的个体化颅内动脉瘤模型:一种在生物学和血流动力学之间架起桥梁的新的体外方法。

A patient-specific intracranial aneurysm model with endothelial lining: a novel in vitro approach to bridge the gap between biology and flow dynamics.

机构信息

Department of Neurosurgery, Jichi Medical University, Shimotsuke, Japan.

Division of Interventional Neuroradiology, University of California, Los Angeles, Los Angeles, California, USA.

出版信息

J Neurointerv Surg. 2018 Mar;10(3):306-309. doi: 10.1136/neurintsurg-2017-013087. Epub 2017 Jun 26.

DOI:10.1136/neurintsurg-2017-013087
PMID:28652298
Abstract

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.

摘要

目的

开发一种体外模型,用于研究三维(3D)患者特定血管几何形状中复杂流应力对内皮细胞的生物学影响。

材料和方法

使用 3D 打印技术从旋转血管造影获得的血管图像数据制造血管复制品。用纤维连接蛋白涂覆血管模型,并将其浸入充满内皮细胞悬浮液的管中,然后在缓慢旋转的三维环境中进行培养。用内皮化血管模型进行带有粘度的培养基循环灌注。使用在流动实验中使用的灌注条件进行计算流体动力学(CFD)研究。在共聚焦显微镜下观察内皮细胞的形态。

结果

CFD 研究表明,基底尖动脉瘤顶点处的壁面切应力和循环流较低,而在母体动脉中存在线性流。共聚焦成像表明,血管模型的内表面均匀地覆盖有单层内皮细胞。在 24 小时的循环流动后,母体动脉中的内皮细胞呈纺锤形并与流动方向一致。相比之下,在动脉瘤顶点处的内皮细胞形状和大小不规则。

结论

成功开发了具有活内皮衬里的几何逼真的颅内动脉瘤模型。这种体外模型为一种新的研究方法提供了可能,将复杂流动对内皮细胞的生物学影响与 CFD 分析和患者信息(包括动脉瘤生长或破裂的存在)相结合进行研究。

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