Abstract
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.
Highlights
Microphysiological systems (MPS), commonly referred to as organs-on-chips or tissue chips, have emerged as a novel approach to create in vitro models of normal and disease physiology
We demonstrate that static co-culture models of the lung air-liquid interface (ALI) and glomerular filtration barrier (GFB) can be transferred to the MPS and exposed to physiomimetic dynamic stimuli
subtractive rapid prototyping (SRP), on the other hand allows for fast, low cost fabrication of microfluidic devices from commonly used plastics that can be are resealable
Summary
Microphysiological systems (MPS), commonly referred to as organs-on-chips or tissue chips, have emerged as a novel approach to create in vitro models of normal and disease physiology. By incorporating human cells into microfluidic devices that recapitulate physiological tissue architecture and dynamic in vivo stimuli, MPS have promised to address the high attrition rate of compounds in drug development by providing a more human-relevant tool to identify therapeutic targets and assess drug toxicity (Bhatia and Ingber, 2014). The rapid development of MPS has been greatly influenced by the widespread use of polydimethylsiloxane (PDMS) as a biocompatible material for microfluidic devices (Duffy et al, 1998; McDonald and Whitesides, 2002; Huh et al, 2013). The widespread adoption of MPS has been hampered by some of the innate properties of PDMS (Berthier et al, 2012). The absorption of small molecules and leaching of uncrosslinked oligomers have provided the greatest hindrance to the adoption of PDMS-based MPS in the context of drug discover assays (van Meer et al, 2017)
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