Project

Pulmonary fibrosis is a chronic and progressive lung disease, whose deadliest and most common form is called idiopathic pulmonary fibrosis (IPF). Although the pathogenesis of IPF is incompletely understood, it is suggested that it is primarily a disease of abnormal alveolar wound repair and remodeling after repeated epithelial microinjuries. Fundamental understanding of the reepithelialization requires advanced alveolar-capillary in vitro models that best reproduce the in vivo microenvironment.

The objective of this project is therefore to develop a microfluidic based lung-on-chip device that has the capability to mimic the in vivo conditions of the alveolar-capillary barrier, including the simulation of the respiratory movements of the lung. As research in this field is at an early stage, the proposed program lies at the forefront of research in this domain. In addition, to the best of our knowledge, the development of such a bioartificial lung-on-chip has never been proposed for therapeutic applications. This novel tool is particularly designed to investigate the pathophysiology of IPF. For this, the epithelial layer of the bioartificial alveolar membrane, ultimately made of human primary cells, will be chemically injured to imitate in vivo fibrosis. The restoration by the epithelial layer will be investigated by accurate delivery of hepatic growth factor (HGF) and/or by co-culturing bone marrow stromal cells, which are expected to contribute to alveolar repair in the injured lung. This advanced lung-on-chip model will thus serve to gain a better understanding of the cellular and molecular mechanisms that take place during fibrosis and during the restoration of the epithelial layer.

It is expected that at the end of the project, the pathophysiology of IPF will be better understood, and most of all, a novel model of a bioartificial alveolar-capillary barrier will be available for further study of fibrosis-like injury on chip.