A lung/liver-on-a-chip platform for acute and chronic toxicity studies

Bovard, David; Sandoz, Antonin; Luettich, Karsta; Frentzel, Stefan; Iskandar, Anita; Marescotti, Diego; Trivedi, Keyur; Guedj, Emmanuel; Dutertre, Quentin; Peitsch, Manuel C.; Hoeng, Julia

doi:10.1039/c8lc01029c

Cited by 145 publications

(131 citation statements)

References 78 publications

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“…Thus, an organ-on-chip makes it possible to study the interactions between multiple organs. A series of multiple organ chips have been established to mimic the physiological environmental systems of multiple organs, such as intestines with the liver [97], nephridium with the liver, and lungs with the liver [98].…”

Section: Drug Screening and Toxicity Testingmentioning

confidence: 99%

“…Liver spheroids were connected in a single circuit, and normal human bronchial epithelial cells were cultured at the air-liquid interface. Aflatoxin B1 (AFB1) toxicity in lung tissues decreased when liver spheroids were present in the same chip circuit, indicating that the liver-mediated detoxification protected lung tissues [98]. The lung/liver-on-a-chip platform presented here offers new opportunities to study the toxicity of inhaled aerosols or to demonstrate the safety and efficacy of new drug candidates targeting the human lung.…”

Section: Fabrication Of Multiple Organs On a Chipmentioning

confidence: 99%

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Engineered Liver-On-A-Chip Platform to Mimic Liver Functions and Its Biomedical Applications: A Review

et al. 2019

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Hepatology and drug development for liver diseases require in vitro liver models. Typical models include 2D planar primary hepatocytes, hepatocyte spheroids, hepatocyte organoids, and liver-on-a-chip. Liver-on-a-chip has emerged as the mainstream model for drug development because it recapitulates the liver microenvironment and has good assay robustness such as reproducibility. Liver-on-a-chip with human primary cells can potentially correlate clinical testing. Liver-on-a-chip can not only predict drug hepatotoxicity and drug metabolism, but also connect other artificial organs on the chip for a human-on-a-chip, which can reflect the overall effect of a drug. Engineering an effective liver-on-a-chip device requires knowledge of multiple disciplines including chemistry, fluidic mechanics, cell biology, electrics, and optics. This review first introduces the physiological microenvironments in the liver, especially the cell composition and its specialized roles, and then summarizes the strategies to build a liver-on-a-chip via microfluidic technologies and its biomedical applications. In addition, the latest advancements of liver-on-a-chip technologies are discussed, which serve as a basis for further liver-on-a-chip research.

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Section: Drug Screening and Toxicity Testingmentioning

confidence: 99%

Section: Fabrication Of Multiple Organs On a Chipmentioning

confidence: 99%

Engineered Liver-On-A-Chip Platform to Mimic Liver Functions and Its Biomedical Applications: A Review

et al. 2019

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“…Although the use of primary cells is limited by difficulties in sample isolation, the small number of cells that can be produced and the large variation between different donors (Skardal et al, 2016), such strategy represents a well-acknowledged in vitro approach in mimicking generic airway models (Rayner et al, 2019) that capture the in vivo environment; a point advocated in recent airway-on-chip designs (Benam et al, 2015). By using NHBE cells, we have thus followed a similar approach, including the recent work of Bovard et al (2018) who developed a lung/liver-on-a-chip platform with NHBE cells to study the toxicity of inhaled aerosols. Moreover, many studies have used such cells as an airway model to study cell exposure to ambient air pollution (Becker et al, 2005), using traditional assays with Transwell inserts.…”

Section: Reconstituting a Bronchial Epithelium On Chipmentioning

confidence: 99%

“…Over the past decade, organ-on-chips have gained momentum in laying the foundations for constructing attractive in vitro models that mimic more realistically physiologically relevant organ functions in humans (Nesmith et al, 2014;Abaci et al, 2015;Bovard et al, 2018;Ronaldson-Bouchard and Vunjak-Novakovic, 2018;Shirure et al, 2018). Such platforms allow in vitro examinations within micro-devices lined with human cells, thereby fostering new physiological insights, in both health and disease, complementary to current tools available for diagnostics and conventional in vitro approaches (Tenenbaum-Katan et al, 2018).…”

Section: Introductionmentioning

confidence: 99%

In situ-Like Aerosol Inhalation Exposure for Cytotoxicity Assessment Using Airway-on-Chips Platforms

Elias-Kirma

Artzy‐Schnirman

Das

et al. 2020

Front. Bioeng. Biotechnol.

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Lung exposure to inhaled particulate matter (PM) is known to injure the airway epithelium via inflammation, a phenomenon linked to increased levels of global morbidity and mortality. To evaluate physiological outcomes following PM exposure and concurrently circumvent the use of animal experiments, in vitro approaches have typically relied on traditional assays with plates or well inserts. Yet, these manifest drawbacks including the inability to capture physiological inhalation conditions and aerosol deposition characteristics relative to in vivo human conditions. Here, we present a novel airway-onchip exposure platform that emulates the epithelium of human bronchial airways with critical cellular barrier functions at an air-liquid interface (ALI). As a proof-of-concept for in vitro lung cytotoxicity testing, we recapitulate a well-characterized cell apoptosis pathway, induced through exposure to 2 µm airborne particles coated with αVR1 antibody that leads to significant loss in cell viability across the recapitulated airway epithelium. Notably, our in vitro inhalation assays enable simultaneous aerosol exposure across multiple airway chips integrated within a larger bronchial airway tree model, under physiological respiratory airflow conditions. Our findings underscore in situ-like aerosol deposition outcomes where patterns depend on respiratory flows across the airway tree geometry and gravitational orientation, as corroborated by concurrent numerical simulations. Our airway-on-chips not only highlight the prospect of realistic in vitro exposure assays in recapitulating characteristic local in vivo deposition outcomes, such platforms open opportunities toward advanced in vitro exposure assays for preclinical cytotoxicity and drug screening applications.

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“…have been reported till date. [ 72–76 ] In addition, these platforms have been used to investigate the migration of cancer cells in a multi‐organ cell environment. [ 77 ] BOC systems have shown great potential in studying organ physiology, tissue development, and disease etiology.…”

Section: Organ‐on‐a‐chipmentioning

confidence: 99%

Emerging Trends in Microfluidics Based Devices

Solanki

Pandey

Gupta

et al. 2020

Biotechnology Journal

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One of the major challenges for scientists and engineers today is to develop technologies for the improvement of human health in both developed and developing countries. However, the need for cost-effective, high-performance diagnostic techniques is very crucial for providing accessible, affordable, and high-quality healthcare devices. In this context, microfluidic-based devices (MFDs) offer powerful platforms for automation and integration of complex tasks onto a single chip. The distinct advantage of MFDs lies in precise control of the sample quantities and flow rate of samples and reagents that enable quantification and detection of analytes with high resolution and sensitivity. With these excellent properties, microfluidics (MFs) have been used for various applications in healthcare, along with other biological and medical areas. This review focuses on the emerging demands of MFs in different fields such as biomedical diagnostics, environmental analysis, food and agriculture research, etc., in the last three or so years. It also aims to reveal new opportunities in these areas and future prospects of commercial MFDs.

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A lung/liver-on-a-chip platform for acute and chronic toxicity studies

Abstract: A lung/liver-on-a-chip platform with metabolic capability over 28 days: a fit-for-purpose microfluidic system for toxicity assessment of pulmonary toxicants.

Cited by 145 publications

References 78 publications

Engineered Liver-On-A-Chip Platform to Mimic Liver Functions and Its Biomedical Applications: A Review

Engineered Liver-On-A-Chip Platform to Mimic Liver Functions and Its Biomedical Applications: A Review

In situ-Like Aerosol Inhalation Exposure for Cytotoxicity Assessment Using Airway-on-Chips Platforms

Emerging Trends in Microfluidics Based Devices

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