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The reproduction of the human lung alveolar barrier in-vitro is a challenging endeavor that is the subject of much research effort worldwide. The complex three-dimensional architecture of the lower airways, the air-liquid interface and the cyclic mechanical strain of the breathing motions makes it a challenging barrier to model in-vitro. Here we report about the development of lung-on-chip models, equipped with thin, flexible and porous membranes that can be cyclically stretched to mimic the breathing motions. A first version of the lung-on-chip system uses a polymeric membrane, whereas a second device integrates a biological membrane made of collagen and elastin. Results with primary lung alveolar epithelial cells from patients co-cultured with primary lung endothelial cells will be presented. Finally, microvascular models mimicking a functional microvasculature network, made of primary endothelial cells and lung pericytes and/or fibroblasts will be shown. The cells seeded in a fibrin gel self-assemble to build a network of functional microvessels of only a few tens of micrometers in diameter. The effect of the cyclic stress of the breathing motions will also be discussed. We could demonstrate that microvessels are perfusable and contract upon exposure to a vasoconstrictor.

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