Novel Microscale Collagen Hydrogels as a Model for Studying Idiopathic Pulmonary Fibrosis

Abstract

Idiopathic pulmonary fibrosis (IPF) is a progressive fibrotic disease that slowly asphyxiates patients through pathogenic collagen production in the alveolar space, stiffening the tissue and limiting lung capacity. Only two therapeutics are currently approved for use and merely manage disease progression, aiding in neither reversal nor termination of fibrotic spread. Current model systems of IPF are neither physiologically relevant nor recapitulative of patients' response to therapeutics. Coupled with limited treatment options, this points to a need for improved systems to probe IPF pathology and develop effective therapeutics. We have established a novel culture system that enabled the development of a highly scalable and physiologically relevant disease model to recapitulate disease initiation and progression and will allow for systematic probing of the driving factors that sustain fibrosis. With this model, we optimized assays to distinguish between normal and fibrotic microtissues, demonstrated the utility of the platform for drug screening, and found that epigenetic modifiers were able to prevent fibrotic development of microtissues containing primary IPF cells. We also advanced single cell encapsulation and culture methodologies within collagen-based microtissues to probe heterogeneity amongst fibrotic cells.