Modular Microphysiological System for Modeling of Biologic Barrier Function.
Modular Microphysiological System for Modeling of Biologic Barrier Function.
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DOI：
10.3389/fbioe.2020.581163
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发表时间：
2020
影响因子：
5.7
通讯作者：
Agarwal A
中科院分区：
文献类型：
--
作者：
Ishahak M;Hill J;Amin Q;Wubker L;Hernandez A;Mitrofanova A;Sloan A;Fornoni A;Agarwal A
微生理学系统，也称为器官芯片，是设计用于体外模拟人体生理学的微流体装置。聚二甲基硅氧烷（PDMS）是用于芯片上器官的最广泛使用的材料，这是由于已建立的微制造方法以及使其适合于生物应用的性质，例如低细胞毒性、光学透明性、气体渗透性。然而，小分子的吸收和未交联的低聚物的浸出可能会阻碍基于PDMS的器官芯片用于药物发现测定。在这里，我们设计了一个模块化的，无PDMS的微生理系统，能够重现基于PDMS的设备中通常展示的生物屏障功能。我们的微生理学系统由容纳细胞培养物的微流控芯片和通过可编程压力和剪切应力驱动流动的气动微流控泵组成。模块化架构和可编程泵使我们能够模拟多种体内微环境。首先，我们展示了在培养膜上产生循环应变的能力，并建立了肺泡气液界面的模型。接下来，我们利用三维有限元分析建模来表征装置内的流体动力学，并开发在肾小球滤过屏障处发生的压力驱动滤过的模型。最后，我们证明我们的模型可以用来概括鞘脂诱导的肾损伤。总之，我们的研究结果表明，可以部署一个多功能和模块化的微生理系统，而不使用PDMS。此外，在我们的微流体装置中使用的生物惰性塑料适用于各种已建立的高通量制造技术，例如注塑成型。因此，塑料芯片上器官的发展提供了一种途径，以满足日益增长的需求芯片上器官技术。
Microphysiological systems, also known as organs-on-chips, are microfluidic devices designed to model human physiology in vitro. Polydimethylsiloxane (PDMS) is the most widely used material for organs-on-chips due to established microfabrication methods, and properties that make it suitable for biological applications such as low cytotoxicity, optical transparency, gas permeability. However, absorption of small molecules and leaching of uncrosslinked oligomers might hinder the adoption of PDMS-based organs-on-chips for drug discovery assays. Here, we have engineered a modular, PDMS-free microphysiological system that is capable of recapitulating biologic barrier functions commonly demonstrated in PDMS-based devices. Our microphysiological system is comprised of a microfluidic chip to house cell cultures and pneumatic microfluidic pumps to drive flow with programmable pressure and shear stress. The modular architecture and programmable pumps enabled us to model multiple in vivo microenvironments. First, we demonstrate the ability to generate cyclic strain on the culture membrane and establish a model of the alveolar air-liquid interface. Next, we utilized three-dimensional finite element analysis modeling to characterize the fluid dynamics within the device and develop a model of the pressure-driven filtration that occurs at the glomerular filtration barrier. Finally, we demonstrate that our model can be used to recapitulate sphingolipid induced kidney injury. Together, our results demonstrate that a multifunctional and modular microphysiological system can be deployed without the use of PDMS. Further, the bio-inert plastic used in our microfluidic device is amenable to various established, high-throughput manufacturing techniques, such as injection molding. As a result, the development plastic organs-on-chips provides an avenue to meet the increasing demand for organ-on-chip technology.
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影响因子：
6.1
作者：
Sip CG;Bhattacharjee N;Folch A
通讯作者：
Folch A
DOI：
10.1177/2211068214561025
发表时间：
2015-04
期刊：
Journal of laboratory automation
影响因子：
--
作者：
Srinivasan B;Kolli AR;Esch MB;Abaci HE;Shuler ML;Hickman JJ
通讯作者：
Hickman JJ
影响因子：
64.8
作者：
OLIVERA, A;SPIEGEL, S
通讯作者：
SPIEGEL, S
DOI：
10.1152/ajplung.00104.2004
发表时间：
2005-01-01
影响因子：
4.9
作者：
Lu, WJ;Lillehoj, EP;Kim, KC
通讯作者：
Kim, KC
DOI：
10.1073/pnas.0610868104
发表时间：
2007-11-27
影响因子：
11.1
作者：
Huh, Dongeun;Fujioka, Hideki;Takayama, Shuichi
通讯作者：
Takayama, Shuichi