北京生物医学工程

体外仿生三维血管生成微流控芯片的构建

Construction of a biomimetic 3D angiogenesis microfluidic chip

作者：司清蕊陈卫星刘冉

单位：清华大学医学院生物医学工程系（北京１０００８４）

关键词：体外仿生；三维血管；微流控芯片；双管道芯片；物质扩散；血管出芽

分类号：R318.04

出版年·卷·期（页码）：2020·39·1（1-7）

摘要：

目的在微流控芯片上构建模拟人体血管的三维血管管道，并实现管道间的物质交换，形成有自主出芽功能的血管，为血管生成相关的疾病机制研究、药物筛选等提供良好的平台工具。方法利用微流控技术，使用人体脐静脉内皮细胞（human umbilical vein endothelial cells ，HUVEC），采用被动进样方式，使内皮细胞在微流控芯片上自主贴壁生长形成三维血管管腔，构建体外仿生三维单管道血管和双管道血管芯片。在此基础上，开展对血管响应刺激因子出芽的功能的验证实验。结果体外仿生的双管道芯片的构建成功率达80%以上。在血管管道，内皮细胞无需借助外力支撑，在芯片上自主形成了直径在300μm±50 μm的宽度均匀的、类似体内血管的三维血管管腔；物质通过模拟体内的扩散过程达到血管管道，使血管管腔响应物质刺激而出现功能性的血管出芽。结论体外仿生三维血管微流控芯片在体外实现了体内血管的结构与功能，模拟了体内物质扩散对血管生成的影响，可以用于生理过程中血管生成的体外动态观察。

Objective To construct three dimensional （3D） vascular lumens on a chip to stimulate the form and functions of blood vessels in vivo and to provide a good platform for the mechanism study, drug screening and dynamic observation of angiogenesis-related processes in vitro. Methods The single-channel and double-channel biomimetic 3D angiogenesis microfluidic chip was constructed by passive pumping method. Human umbilical vein endothelial cells (HUVEC） was seeded in vascular channel and rotated to form a 3D lumen. Then, irritant factor of angiogenesis stimulated the vascular lumen to observe angiogenesis function. Results The success rate of the chip construction was up to 80%. In the vascular channel, HUVEC grew on the wall of the channel to form a 3D vascular lumen autonomously. The diameter of the lumen was 300 μm ± 50 μm. Stimulating factors in the sample channel could reach the vascular channel through a diffusion process, similar to the diffusion process in vivo. And vascular lumen could respond the stimulating factors to form vascular sprouting. Conclusions The 3D angiogenesis microfluidic chip displays the structure and function of blood vessels and simulates the effect of substance diffusion on angiogenesis in vivo, which can be used for dynamic observation of angiogenesis in physiological processes in vitro.

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