Lung-on-a-chip with a biological, stretchable membrane: New generation of in-vitro air-blood barrier model

Standard in vitro model fails to reproduce the complex microenvironment of the lung alveolar barrier, especially the native extracellular matrix (ECM) and its intrinsic properties. Here, we propose a new lung alveolar barrier model based on a biological, thin and stretchable membrane. It is made of collagen and elastin, which provide the stability and elasticity to the membrane. In order to recreate the structure and the dimension of single alveoli, the membrane is supported by an array of hexagonal gold mesh, with holes of about 260mm, over which the membrane is suspended. Human lung alveolar epithelial primary type II cells isolated from healthy lung resections and primary human lung microvascular endothelial cells are cultured on each sides of the membrane. It allows to recreate an air blood barrier without any artificial layer between the epithelium and the endothelium. The membrane is a suitable biological support able to recreate the dynamic microenvironment of the lung, with the reproduction of the breathing movements. It is permeable, which makes it possible to culture cells at the air-liquid interface. Cells from several patients have been cultured on the membrane, which resulted in tight barrier properties. The developed membrane is very simple to produce, cost-efficient and with suitable geometrical, biophysical, mechanical and transport properties of the lung alveolar barrier. Its biological nature makes this model a promising tool for drug discovery and precision medicine.