Abstract
Organs-on-chips are microfluidic devices typically fabricated from polydimethylsiloxane (PDMS). Since PDMS has many attractive properties including high optical clarity and compliance, PDMS is very useful for cell culture applications; however, PDMS possesses a significant drawback in that small hydrophobic molecules are strongly absorbed. This drawback hinders widespread use of PDMS-based devices for drug discovery and development. Here, we describe a microfluidic cell culture system made of a tetrafluoroethylene-propylene (FEPM) elastomer. We demonstrated that FEPM does not absorb small hydrophobic compounds including rhodamine B and three types of drugs, nifedipine, coumarin, and Bay K8644, whereas PDMS absorbs them strongly. The device consists of two FEPM layers of microchannels separated by a thin collagen vitrigel membrane. Since FEPM is flexible and biocompatible, this microfluidic device can be used to culture cells while applying mechanical strain. When human umbilical vein endothelial cells (HUVECs) were subjected to cyclic strain (~10%) for 4 h in this device, HUVECs reoriented and aligned perpendicularly in response to the cyclic stretch. Moreover, we demonstrated that this device can be used to replicate the epithelial–endothelial interface as well as to provide physiological mechanical strain and fluid flow. This method offers a robust platform to produce organs-on-chips for drug discovery and development.
Highlights
Predicting drug efficacy and toxicity before clinical trials is crucial for the drug discovery and development processes [1,2,3]
To explore whether our microfluidic devices fabricated from fuosrindgruagtdetisrcaoflvueorryoaetnhdydleenvee-lporpompyenletn. e (FEPM) could prevent drug absorption, we compared absorption of a fluorescent dye into microchannels made either of FEPM or PDMS
The fluorescence intensity of the PDMS microchannel gradually increased over time and the bright area gradually spread out, indicating that the PDMS microchannel continuously soaked up the fluorophore
Summary
Predicting drug efficacy and toxicity before clinical trials is crucial for the drug discovery and development processes [1,2,3]. Microfluidic organs-on-chips demonstrated that mechanical forces are important to drive cellular differentiation and function and to faithfully recapitulate human organ-level physiology and pathophysiology; e.g., in lung [15,16,17], gut [18,19], kidney [20,21,22], and cancer models [23]. These microfluidic devices mimicking the mechanical microenvironment of living tissues have great potential to predict human responses to drugs and serve as an alternative to animal models
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