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A modular microfluidic system based on a multilayered configuration to generate large-scale perfusable microvascular networks
Microsystems & Nanoengineering ( IF 7.9 ) Pub Date : 2021-01-06 , DOI: 10.1038/s41378-020-00229-8
Tao Yue 1, 2 , Da Zhao 1 , Duc T T Phan 3 , Xiaolin Wang 4, 5, 6 , Joshua Jonghyun Park 7 , Zayn Biviji 8 , Christopher C W Hughes 1, 3 , Abraham P Lee 1, 9
Affiliation  

The vascular network of the circulatory system plays a vital role in maintaining homeostasis in the human body. In this paper, a novel modular microfluidic system with a vertical two-layered configuration is developed to generate large-scale perfused microvascular networks in vitro. The two-layer polydimethylsiloxane (PDMS) configuration allows the tissue chambers and medium channels not only to be designed and fabricated independently but also to be aligned and bonded accordingly. This method can produce a modular microfluidic system that has high flexibility and scalability to design an integrated platform with multiple perfused vascularized tissues with high densities. The medium channel was designed with a rhombic shape and fabricated to be semiclosed to form a capillary burst valve in the vertical direction, serving as the interface between the medium channels and tissue chambers. Angiogenesis and anastomosis at the vertical interface were successfully achieved by using different combinations of tissue chambers and medium channels. Various large-scale microvascular networks were generated and quantified in terms of vessel length and density. Minimal leakage of the perfused 70-kDa FITC-dextran confirmed the lumenization of the microvascular networks and the formation of tight vertical interconnections between the microvascular networks and medium channels in different structural layers. This platform enables the culturing of interconnected, large-scale perfused vascularized tissue networks with high density and scalability for a wide range of multiorgan-on-a-chip applications, including basic biological studies and drug screening.



中文翻译:

基于多层配置的模块化微流控系统生成大规模可灌注微血管网络

循环系统的血管网络在维持人体体内平衡方面起着至关重要的作用。在本文中,开发了一种具有垂直两层配置的新型模块化微流体系统,用于在体外生成大规模灌注微血管网络。两层聚二甲基硅氧烷 (PDMS) 配置允许组织室和介质通道不仅可以独立设计和制造,而且可以相应地对齐和粘合。该方法可以产生具有高度灵活性和可扩展性的模块化微流体系统,以设计具有多个高密度灌注血管化组织的集成平台。介质通道设计为菱形,制造成半封闭,在垂直方向形成毛细管爆破阀,作为介质通道和组织室之间的界面。通过使用组织室和培养基通道的不同组合,成功实现了垂直界面的血管生成和吻合。根据血管长度和密度生成并量化了各种大规模微血管网络。灌注的 70-kDa FITC-葡聚糖的最小泄漏证实了微血管网络的流明以及微血管网络和不同结构层中的介质通道之间形成紧密的垂直互连。该平台能够培养具有高密度和可扩展性的互连、大规模灌注血管化组织网络,适用于广泛的多器官芯片应用,包括基础生物学研究和药物筛选。

更新日期:2021-01-06
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