A microfluidic platform for generating large-scale nearly identical human microphysiological vascularized tissue arrays.
A microfluidic platform for generating large-scale nearly identical human microphysiological vascularized tissue arrays.
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DOI：
10.1039/c3lc50424g
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发表时间：
2013-08-07
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：
Hsu YH;Moya ML;Hughes CC;George SC;Lee AP
本文报道了一种聚二甲基硅氧烷微流体模型系统，它可以开发出具有相互连接的血管网络的几乎相同的人体微组织阵列。微流控系统的设计是基于与电路的类比，应用阻性电路的概念来设计串联微组织腔中的分压计。长的微通道(550、620和775 mm)形成具有大液压阻力的阻性回路。两个截面积大、高度不同的介质油藏连接到长微通道的进出口，作为压力源，沿长微通道形成近乎恒定的压降。微组织腔(0.12μL)用作两端电阻元件，其输入阻抗是长微通道的50倍。将每个微组织腔连接到沿着长微通道的两个不同位置，产生了一系列的压力分隔器。每个微组织腔能够在不改变微通道的流体动力学行为的情况下控制微通道的一段的压降。其结果是在微腔内形成了可控和可预测的微生理环境。通过有限元模拟和实验验证了间质流动是一种刺激血管生成的机械信号。这种设计的简单性使得能够通过在两周和三周的时间内在微腔内共培养内皮细胞、基质细胞和纤维蛋白来开发多个微组织阵列(5、12和30个微组织)。这种方法能够培养大量具有相互连接的血管网络的微组织，用于生物学研究和药物开发等应用。
This paper reports a polydimethylsiloxane microfluidic model system that can develop an array of nearly identical human microtissues with interconnected vascular networks. The microfluidic system design is based on an analogy with an electric circuit, applying resistive circuit concepts to design pressure dividers in serially-connected microtissue chambers. A long microchannel (550, 620 and 775 mm) creates a resistive circuit with a large hydraulic resistance. Two media reservoirs with a large cross-sectional area and of different heights are connected to the entrance and exit of the long microchannel to serve as a pressure source, and create a near constant pressure drop along the long microchannel. Microtissue chambers (0.12 μl) serve as a two-terminal resistive component with an input impedance > 50-fold larger than the long microchannel. Connecting each microtissue chamber to two different positions along the long microchannel creates a series of pressure dividers. Each microtissue chamber enables a controlled pressure drop of a segment of the microchannel without altering the hydrodynamic behaviour of the microchannel. The result is a controlled and predictable microphysiological environment within the microchamber. Interstitial flow, a mechanical cue for stimulating vasculogenesis, was verified by finite element simulation and experiments. The simplicity of this design enabled the development of multiple microtissue arrays (5, 12, and 30 microtissues) by co-culturing endothelial cells, stromal cells, and fibrin within the microchambers over two and three week periods. This methodology enables the culturing of a large array of microtissues with interconnected vascular networks for biological studies and applications such as drug development.
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影响因子：
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