Abstract
The air-blood barrier with its complex architecture and dynamic environment is difficult to mimic in vitro. Lung-on-a-chips enable mimicking the breathing movements using a thin, stretchable PDMS membrane. However, they fail to reproduce the characteristic alveoli network as well as the biochemical and physical properties of the alveolar basal membrane. Here, we present a lung-on-a-chip, based on a biological, stretchable and biodegradable membrane made of collagen and elastin, that emulates an array of tiny alveoli with in vivo-like dimensions. This membrane outperforms PDMS in many ways: it does not absorb rhodamine-B, is biodegradable, is created by a simple method, and can easily be tuned to modify its thickness, composition and stiffness. The air-blood barrier is reconstituted using primary lung alveolar epithelial cells from patients and primary lung endothelial cells. Typical alveolar epithelial cell markers are expressed, while the barrier properties are preserved for up to 3 weeks.
Highlights
The air-blood barrier with its complex architecture and dynamic environment is difficult to mimic in vitro
We report about a lung-on-a-chip of the second generation that mimics the following central aspects of the air–blood barrier: (1) an array of alveoli, with dimensions similar to those found in vivo and (2) a biological membrane made of proteins of the lung extracellular matrix (ECM), collagen and elastin, enabling the membrane to be
First-generation lung-on-a-chip devices imitate the rhythmic mechanical strain of the alveolar barrier induced by breathing motions[8,9]
Summary
The air-blood barrier with its complex architecture and dynamic environment is difficult to mimic in vitro. Lung-on-a-chips enable mimicking the breathing movements using a thin, stretchable PDMS membrane They fail to reproduce the characteristic alveoli network as well as the biochemical and physical properties of the alveolar basal membrane. Organs-on-chips (OOCs) are emerging as predictive tissue modelling tools and as a credible alternative to animal testing These micro-engineered cell-based systems provide cells with an environment that closely resembles their native in vivo milieu[1,2,3]. Hydrogels receive a strong interest to recreate the chemical composition and structure of the native ECM in cell culture systems[20,21] Their intrinsic properties, including mechanical features, chemical composition and porosity, make them ideal candidates to supersede PDMS membranes[22]. Collagen vitrified membrane[24] has been integrated into microfluidic devices for use as cell culture substrates[25,26], but, to the best of our knowledge, no stretchable membranes have been reported so far
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