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使用三维明胶芯片与 TiC/C 纳米线阵列微电极进行血管内腔模拟和高灵敏度一氧化氮检测。

Vascular lumen simulation and highly-sensitive nitric oxide detection using three-dimensional gelatin chip coupled to TiC/C nanowire arrays microelectrode.

机构信息

Key Laboratory of Analytical Chemistry for Biology and Medicine (Ministry of Education), College of Chemistry and Molecular Sciences, Wuhan University, Wuhan, 430072, China.

出版信息

Lab Chip. 2012 Nov 7;12(21):4249-56. doi: 10.1039/c2lc40148g.

Abstract

Reproducing the physiological environment of blood vessels for the in vitro investigation of endothelial cell functions is very challenging. Here, we describe a vascular-like structure based on a three-dimensional (3D) gelatin chip with good compatibility and permeability which is also cost-effective and easy to produce. The controllable lumen diameter and wall thickness enable close mimicking of blood vessels in vitro. The 3D gelatin matrix between adjacent lumens is capable of generating soluble-factor gradients inside, and diffusion of molecules with different molecular weights through the matrix is studied. The cultured human umbilical vein endothelial cells proliferate on the gelatin lumen linings to form a vascular lumen. The hemodynamic behavior including adhesion, alignment of endothelial cells (ECs) under shear stress and pulsatile stretch is studied. Furthermore, a microelectrode comprising TiC/C nanowire arrays is fabricated to detect nitric oxide with sub-nM detection limits and NO generation from the cultured ECs is monitored in real time. This vascular model reproduces the surrounding parenchyma of endothelial cells and mimics the hemodynamics inside blood vessels very well, thereby enabling potential direct investigation of hemodynamics, angiogenesis, and tumor metastasis in vitro.

摘要

在体外研究内皮细胞功能时,复制血管的生理环境极具挑战性。在这里,我们描述了一种基于具有良好相容性和通透性的三维(3D)明胶芯片的类似血管的结构,该结构具有成本效益且易于制作。可控制的管腔直径和壁厚使体外血管能够得到很好的模拟。相邻管腔之间的 3D 明胶基质能够在内部产生可溶性因子梯度,并研究不同分子量的分子通过基质的扩散。培养的人脐静脉内皮细胞在明胶管腔衬里上增殖,形成血管腔。研究了包括粘附、剪切力下内皮细胞(ECs)的取向和脉动拉伸在内的血液动力学行为。此外,还制备了包含 TiC/C 纳米线阵列的微电极来检测亚纳摩尔检测限的一氧化氮,并且可以实时监测培养的 ECs 产生的 NO。该血管模型再现了内皮细胞周围的实质组织,并很好地模拟了血管内的血液动力学,从而能够直接研究体外血液动力学、血管生成和肿瘤转移。

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