Fibrosis-on-Chip: A Guide to Recapitulate the Essential Features of Fibrotic Disease.

Fibrosis, which is primarily marked by excessive extracellular matrix (ECM) deposition, is a pathophysiological process associated with many disorders, which ultimately leads to organ dysfunction and poor patient outcomes. Despite the high prevalence of fibrosis, currently there exist few therapeutic options, and importantly, there is a paucity of in vitro models to accurately study fibrosis. This review discusses the multifaceted nature of fibrosis from the viewpoint of developing organ-on-chip (OoC) disease models, focusing on five key features: the ECM component, inflammation, mechanical cues, hypoxia and vascularization. We explore the potential of OoC technology for better modeling these features in the context of studying fibrotic diseases and emphasize the interplay between various key features. We review how organ-specific fibrotic diseases have been modeled in OoC platforms, which elements have been included in these existing models, and we highlight avenues for novel research directions. Finally, we conclude with a perspective section on how to address the current gap with respect to the inclusion of multiple features to yield more sophisticated and relevant models of fibrotic diseases in an OoC format. This article is protected by copyright. All rights reserved.