MIMICKING THE LUNG ALVEOLAR ENVIRONMENT WITH ORGANS-ON-CHIP TECHNOLOGIES

The complex tree-like architecture of the lungs that ends with tiny alveolar sacs is difficult to mimic in-vitro. The delicate and ultra-thin alveolar barrier with its air-liquid interface is constantly exposed to the rhythmic respiratory movements. We report here about two organs-on-chip models that uniquely reproduce this environment and in which patients 'cells are cultured. A first model recapitulates an array of alveoli with in-vivo dimensions using a biological stretchable membrane. The second model mimics a functional lung capillary network. The key part of the lung alveolar model is a biological membrane made of collagen and elastin (CE) that is pipetted on a gold mesh, whose pores correspond to the alveolar size (about 200um). Once the dried CE-membrane is rehydrated, primary human cells (alveolar epithelial and endothelial) can be cultured on both sides. The second model is based on the self-assembly of endothelial cells and pericytes that are confined in fibrin gel in microengineered compartments. A functional alveolar barrier made of primary human alveolar epithelial cells and lung endothelial cells is reported. The CE-membrane, on which the cells are cultured, is thin (a few micrometers), porous (enables the culture of cells at the air-liquid interface during several days), and stretchable. The reported lung microvasculature made of self-assembled endothelial cells and pericytes is perfusable, vasoactive (contracts in presence of phenylephrine, a vasoconstrictor) and is permeable. These advanced in-vitro models enable mimicking the lung parenchymal environment in an unprecedented way. As a result, the cultured tissues made of primary human lung cells are able to maintain organ-specific functions, such as air-blood barrier tightness and microvascular perfusability and contractility. Organs-on-chip solutions, such as those presented here, may open new possibilities for specific tissue engineering applications.