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Pumpless, modular, microphysiological systems enabling tunable perfusion for long-term cultivation of endothelialized lumens
Biomedical Microdevices ( IF 3.0 ) Pub Date : 2021-04-14 , DOI: 10.1007/s10544-021-00562-3
James J Tronolone 1 , Johnny Lam 1 , Anant Agrawal 2 , Kyung Sung 1
Affiliation  

Given the increased recognition of the importance of physiologically relevant microenvironments when designing in vitro assays, microphysiological systems (MPS) that mimic the critical function and structure of tissues and organs have gained considerable attention as alternatives to traditional experimental models. Accordingly, the field is growing rapidly, and some promising MPS are being tested for use in pharmaceutical development and toxicological testing. However, most MPS are complex and require additional infrastructure, which limits their successful translation. Here, we present a pumpless, modular MPS consisting of 1) a resistance module that controls flow rate and 2) a physiologically relevant, three-dimensional blood vessel module. Flow is provided by an attached reservoir tank that feeds fluid into the resistance channel via hydrostatic pressure. The flow rate is controlled by the height of the media in the tank and the resistance channel’s dimensions. The flow from the resistance module is streamed into the blood vessel module using a liquid bridge. We utilize optical coherence tomography (OCT) to measure fluid velocity at regions of interest. The endothelial cells cultured in the MPS remain viable for up to 14 days and demonstrate the functional characteristics of the human blood vessels verified by tight junction expression and diffusion assay. Our results show that a modular MPS can simulate a functional endothelium in vitro while simplifying the operation of the MPS. The simplicity of the system allows for modifications to incorporate other microenvironmental components and to build other organ-modeling systems easily.



中文翻译:

无泵、模块化、微生理系统可实现可调节灌注,用于内皮化管腔的长期培养

鉴于在体外设计时越来越认识到生理相关微环境的重要性作为传统实验模型的替代品,模拟组织和器官的关键功能和结构的微生理系统 (MPS) 已经获得了相当多的关注。因此,该领域正在迅速发展,一些有前途的 MPS 正在测试用于药物开发和毒理学测试。然而,大多数 MPS 很复杂,需要额外的基础设施,这限制了它们的成功翻译。在这里,我们提出了一个无泵的模块化 MPS,包括 1) 控制流速的阻力模块和 2) 生理相关的三维血管模块。流体由连接的储液罐提供,该储液罐通过静水压力将流体送入阻力通道。流速由罐中介质的高度和阻力通道的尺寸控制。来自阻力模块的流使用液桥流入血管模块。我们利用光学相干断层扫描 (OCT) 来测量感兴趣区域的流体速度。在 MPS 中培养的内皮细胞可以存活长达 14 天,并证明了通过紧密连接表达和扩散测定验证的人类血管的功能特征。我们的结果表明模块化 MPS 可以模拟功能性内皮 在 MPS 中培养的内皮细胞保持活力长达 14 天,并证明了通过紧密连接表达和扩散测定验证的人类血管的功能特征。我们的结果表明模块化 MPS 可以模拟功能性内皮 在 MPS 中培养的内皮细胞可以存活长达 14 天,并证明了通过紧密连接表达和扩散测定验证的人类血管的功能特征。我们的结果表明模块化 MPS 可以模拟功能性内皮在体外,同时简化了MPS的操作。该系统的简单性允许修改以合并其他微环境组件并轻松构建其他器官建模系统。

更新日期:2021-04-15
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