Airway-On-A-Chip: Designs and Applications for Lung Repair and Disease

Bennet, Tanya J.; Randhawa, Avineet; Hua, Jessica; Cheung, Karen C.

doi:10.3390/cells10071602

Cited by 41 publications

(18 citation statements)

References 258 publications

(500 reference statements)

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“…However, these interactions are vital in organ engineering and developing novel 3D ex vivo models such as organoids and lung-onchip that help to test and develop new possible medications. These modern models have great importance since they provide a 3D structure that mimics the lung microenvironment and the organ complexity in which cells interact with the surrounding extracellular matrix and the external environment without losing close interaction with each other (54,65).…”

Section: The Effects Of Airway Smooth Muscle Cells On Epithelial Cellsmentioning

confidence: 99%

Crosstalk of Airway Smooth Muscle and Epithelial Cells in Chronic Lung Diseases

Abohalaka¹

2022

Preprint

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Chronic pulmonary diseases such as asthma, COPD, and Idiopathic pulmonary fibrosis are significant causes of mortality and morbidity worldwide. Currently, there is no radical treatment for many chronic pulmonary diseases, and the treatment options focus on relieving the symptoms and improving lung function. Therefore, efficient therapeutic agents are highly needed. Bronchial epithelial cells and airway smooth muscle cells and their crosstalk play a significant role in the pathogenesis of these diseases. Thus, targeting the interactions of these two cell types could open the door to a new generation of effective therapeutic options. However, the studies on how these two cell types interact and how their crosstalk adds up to respiratory diseases are not well established. With the rise of modern research tools and technology, such as lab-on-chip, organoids, co-culture techniques, and advanced immunofluorescence imaging, a substantial degree of evidence about these cell interactions emerged. Hence, this contribution aims to review the growing evidence of bronchial epithelial cells and airway smooth muscle cells crosstalk under normal and pathophysiological conditions. The review first deliberates the effects of both healthy and stressed epithelial cells on airway smooth muscle cells, taking into account three themes; contraction, migration, and proliferation. Then, it discusses the impact of airway smooth muscle cells on the epithelium in inflammatory settings. Later, it examines the role of airway smooth muscle cells in the early development of bronchial epithelial cells and their recovery after injury.

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Section: The Effects Of Airway Smooth Muscle Cells On Epithelial Cellsmentioning

confidence: 99%

Crosstalk of Airway Smooth Muscle and Epithelial Cells in Chronic Lung Diseases

Abohalaka¹

2022

Preprint

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“…An exciting and promising development in the field of in vitro models are organ-on-a-chip (OoC) models. − This includes OoC models of (tissues of) the lung. − The desired and essential physiological realism in OoCs can be accomplished basically by two approaches: (i) correspondingly high biological complexity or (ii) artificially engineered physiologically relevant microenvironments mimicking geometrical, mechanical, or biochemical key aspects of the tissue or organ of interest . The first approach means in the first instance complex multicellular (coculture) systems.…”

Section: Introductionmentioning

confidence: 99%

3D Lung-on-Chip Model Based on Biomimetically Microcurved Culture Membranes

Baptista

Teixeira

Barata

et al. 2022

ACS Biomater. Sci. Eng.

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A comparatively straightforward approach to accomplish more physiological realism in organ-on-a-chip (OoC) models is through substrate geometry. There is increasing evidence that the strongly, microscale curved surfaces that epithelial or endothelial cells experience when lining small body lumens, such as the alveoli or blood vessels, impact their behavior. However, the most commonly used cell culture substrates for modeling of these human tissue barriers in OoCs, ion track-etched porous membranes, provide only flat surfaces. Here, we propose a more realistic culture environment for alveolar cells based on biomimetically microcurved track-etched membranes. They recreate the mainly spherical geometry of the cells’ native microenvironment. In this feasibility study, the membranes were given the shape of hexagonally arrayed hemispherical microwells by an innovative combination of three-dimensional (3D) microfilm (thermo)forming and ion track technology. Integrated in microfluidic chips, they separated a top from a bottom cell culture chamber. The microcurved membranes were seeded by infusion with primary human alveolar epithelial cells. Despite the pronounced topology, the cells fully lined the alveoli-like microwell structures on the membranes’ top side. The confluent curved epithelial cell monolayers could be cultured successfully at the air−liquid interface for 14 days. Similarly, the top and bottom sides of the microcurved membranes were seeded with cells from the Calu-3 lung epithelial cell line and human lung microvascular endothelial cells, respectively. Thereby, the latter lined the interalveolar septum-like interspace between the microwells in a network-type fashion, as in the natural counterpart. The coculture was maintained for 11 days. The presented 3D lung-on-a-chip model might set the stage for other (micro)anatomically inspired membrane-based OoCs in the future.

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“…They have the potential to better represent the in vivo condition, with applications ranging from drug screening to disease modeling [ 2 , 3 ]. Additionally, microfluidic systems can integrate a plethora of microsensors for continuous monitoring of multiple culture metrics—from excretion of soluble biomarkers to trans-epithelial electrical resistance [ 4 , 5 ]. The continued development and refinement of microfluidic systems is well positioned to make a valuable contribution to drug discovery.…”

Section: Introductionmentioning

confidence: 99%

PDMS Organ-On-Chip Design and Fabrication: Strategies for Improving Fluidic Integration and Chip Robustness of Rapidly Prototyped Microfluidic In Vitro Models

et al. 2022

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The PDMS-based microfluidic organ-on-chip platform represents an exciting paradigm that has enjoyed a rapid rise in popularity and adoption. A particularly promising element of this platform is its amenability to rapid manufacturing strategies, which can enable quick adaptations through iterative prototyping. These strategies, however, come with challenges; fluid flow, for example, a core principle of organs-on-chip and the physiology they aim to model, necessitates robust, leak-free channels for potentially long (multi-week) culture durations. In this report, we describe microfluidic chip fabrication methods and strategies that are aimed at overcoming these difficulties; we employ a subset of these strategies to a blood–brain-barrier-on-chip, with others applied to a small-airway-on-chip. Design approaches are detailed with considerations presented for readers. Results pertaining to fabrication parameters we aimed to improve (e.g., the thickness uniformity of molded PDMS), as well as illustrative results pertaining to the establishment of cell cultures using these methods will also be presented.

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Airway-On-A-Chip: Designs and Applications for Lung Repair and Disease

Cited by 41 publications

References 258 publications

Crosstalk of Airway Smooth Muscle and Epithelial Cells in Chronic Lung Diseases

Crosstalk of Airway Smooth Muscle and Epithelial Cells in Chronic Lung Diseases

3D Lung-on-Chip Model Based on Biomimetically Microcurved Culture Membranes

PDMS Organ-On-Chip Design and Fabrication: Strategies for Improving Fluidic Integration and Chip Robustness of Rapidly Prototyped Microfluidic In Vitro Models

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