Engineering anastomosis between living capillary networks and endothelial cell-lined microfluidic channels.
Engineering anastomosis between living capillary networks and endothelial cell-lined microfluidic channels.
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DOI：
10.1039/c5lc01050k
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发表时间：
2016-01-21
期刊：
影响因子：
6.1
通讯作者：
Lee AP
中科院分区：
文献类型：
--
作者：
Wang X;Phan DT;Sobrino A;George SC;Hughes CC;Lee AP
本文报道了一种方法，用于产生一个完整的和灌注的微血管网络连接到微流体通道没有明显的泄漏。该平台整合了血管发育的不同阶段，包括血管发生、内皮细胞（EC）衬里、出芽血管生成和吻合。在组织腔室内通过血管发生形成毛细血管网络之后，相邻的微流体通道衬有单层EC，其然后用作高压输入（“动脉”）和低压输出（“静脉”）导管。为了促进动脉/静脉和毛细血管网络之间的紧密互连，诱导萌芽血管生成，这促进组织腔室内的脉管系统与沿着沿着微流体通道的EC衬里的吻合。荧光微粒的流动证实了管腔化微血管网络的可灌注性，并且70 kDa FITC-葡聚糖的最小泄漏证实了EC连接的生理紧密性和动脉/静脉与毛细血管网络之间的互连的完整性。这种通用的装置设计及其稳健的构造方法建立了从动脉到血管化组织再到静脉的互连灌注血管的生理运输模型。该系统在广泛的器官芯片应用中具有实用性，因为它能够实现多个芯片上组织构建体的生理血管互连，这些组织构建体可以用作药物筛选的疾病模型。一种先进的三维微血管网络模型，通过组织腔包埋的毛细血管网络和内皮细胞内衬的微流体通道之间的工程生理吻合实现。
This paper reports a method for generating an intact and perfusable microvascular network that connects to microfluidic channels without appreciable leakage. This platform incorporates different stages of vascular development including vasculogenesis, endothelial cell (EC) lining, sprouting angiogenesis, and anastomosis in sequential order. After formation of a capillary network inside the tissue chamber via vasculogenesis, the adjacent microfluidic channels are lined with a monolayer of ECs, which then serve as the high-pressure input (“artery”) and low pressure output (“vein”) conduits. To promote a tight interconnection between the artery/vein and the capillary network, sprouting angiogenesis is induced, which promotes anastomosis of the vasculature inside the tissue chamber with the EC lining along the microfluidic channels. Flow of fluorescent microparticles confirms the perfusability of the lumenized microvascular network, and minimal leakage of 70 kDa FITC-dextran confirms physiologic tightness of the EC junctions and completeness of the interconnections between artery/vein and the capillary network. This versatile device design and its robust construction methodology establish a physiological transport model of interconnected perfused vessels from artery to vascularized tissue to vein. The system has utility in a wide range of organ-on-a-chip applications as it enables the physiological vascular interconnection of multiple on-chip tissue constructs that can serve as disease models for drug screening. An advanced 3D microvascular network model enabled by engineering physiological anastomosis between tissue chamber-embedded capillary network and endothelial cell-lined microfluidic channels.