Abstract
The lungs are affected by illnesses including asthma, chronic obstructive pulmonary disease, and infections such as influenza and SARS-CoV-2. Physiologically relevant models for respiratory conditions will be essential for new drug development. The composition and structure of the lung extracellular matrix (ECM) plays a major role in the function of the lung tissue and cells. Lung-on-chip models have been developed to address some of the limitations of current two-dimensional in vitro models. In this review, we describe various ECM substitutes utilized for modeling the respiratory system. We explore the application of lung-on-chip models to the study of cigarette smoke and electronic cigarette vapor. We discuss the challenges and opportunities related to model characterization with an emphasis on in situ characterization methods, both established and emerging. We discuss how further advancements in the field, through the incorporation of interstitial cells and ECM, have the potential to provide an effective tool for interrogating lung biology and disease, especially the mechanisms that involve the interstitial elements.
Highlights
The lung has a complex multicellular 3-dimensional (3D) architecture in which cells interact with each other, the surrounding extracellular matrix (ECM), and the external environment
Increase in MMP-9 and IL-8 release with exposure to eCVE
Viability and barrier integrity decreased with exposure to certain flavors, one of which led to an increase in IL-8 and MCP-1 release
Summary
The lung has a complex multicellular 3-dimensional (3D) architecture in which cells interact with each other, the surrounding extracellular matrix (ECM), and the external environment. These interactions are crucial for the development, maintenance, and regulation of the structures and functions of the lung [1]. The conducting and respiratory airways are lined with a highly specialized epithelium that interfaces with both the internal microenvironment and the external environment. Widely used in vitro models simplify the microarchitecture, cellular composition, ECM, and/or microenvironment These simplifications limit the ability to replicate complex interactions between cells, the extracellular matrix, and the microenvironment that are necessary to obtain organ function and investigate airway biology
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