Beijing Advanced Innovation Centre for Biomedical Engineering, Key Laboratory for Biomechanics and Mechanobiology of Chinese Education Ministry, School of Biological Science and Medical Engineering, Beihang University.
Beijing Advanced Innovation Centre for Biomedical Engineering, Key Laboratory for Biomechanics and Mechanobiology of Chinese Education Ministry, School of Biological Science and Medical Engineering, Beihang University;
J Vis Exp. 2021 Apr 10(170). doi: 10.3791/62003.
Neovascularization is usually initialized from an existing normal vasculature and the biomechanical microenvironment of endothelial cells (ECs) in the initial stage varies dramatically from the following process of neovascularization. Although there are plenty of models to simulate different stages of neovascularization, an in vitro 3D model that capitulates the initial process of neovascularization under the corresponding stimulations of normal vasculature microenvironments is still lacking. Here, we reconstructed an in vitro 3D model that mimics the initial event of neovascularization (MIEN). The MIEN model contains a microfluidic sprouting chip and an automatic control, highly efficient circulation system. A functional, perfusable microchannel coated with endothelium was formed and the process of sprouting was simulated in the microfluidic sprouting chip. The initially physiological microenvironment of neovascularization was recapitulated with the microfluidic control system, by which ECs would be exposed to high luminal shear stress, physiological transendothelial flow, and various vascular endothelial growth factor (VEGF) distributions simultaneously. The MIEN model can be readily applied to the study of neovascularization mechanism and holds a potential promise as a low-cost platform for drug screening and toxicology applications.
血管新生通常是从现有的正常脉管系统开始的，内皮细胞（ECs）在初始阶段的生物力学微环境与随后的血管新生过程有很大的不同。尽管有大量的模型可以模拟血管新生的不同阶段，但仍然缺乏能够模拟正常脉管环境相应刺激下血管新生初始过程的体外 3D 模型。在这里，我们构建了一种模拟血管新生初始事件（MIEN）的体外 3D 模型。MIEN 模型包含一个微流控发芽芯片和一个自动控制、高效循环系统。在微流控发芽芯片中形成了一个功能性、可灌注的涂有内皮细胞的微通道，并模拟了发芽过程。通过微流控控制系统再现了最初的血管新生生理微环境，使 ECs 同时暴露于高腔内剪切应力、生理跨内皮流和各种血管内皮生长因子（VEGF）分布中。MIEN 模型可方便地应用于血管新生机制的研究，并有望成为一种低成本的药物筛选和毒理学应用平台。
