Fibrosis on a Chip for Screening of Anti-Fibrosis Drugs.

Idiopathic pulmonary fibrosis (IPF) is a chronic pathological disorder that targets alveoli interstitial tissues and is characterized by the progressive stiffening of alveolar membrane. The median survival rate of the patients with IPF is less than 5 years. Currently, IPF has no cure and there are few options to alleviate the progress of this disease. A critical roadblock in developing new anti-fibrosis therapies is the absence of reliable cell based in vitro models that can recapitulate the progressive features of this disease. Here a novel fibrotic microtissue on a chip system is created to model the fibrotic transition of the lung interstitial tissue and the effect of anti-fibrosis drugs on such transitions. This system will not only help to expedite the efficacy analysis of anti-fibrotic therapies but also help to unveil their potential mode of action.

Fibrotic microtissue array to predict anti-fibrosis drug efficacy.

Fibrosis is a severe health problem characterized by progressive stiffening of tissues which causes organ malfunction and failure. A major bottleneck in developing new anti-fibrosis therapies is the lack of in vitro models that recapitulate dynamic changes in tissue mechanics during fibrogenesis. Here we create membranous human lung microtissues to model key biomechanical events occurred during lung fibrogenesis including progressive stiffening and contraction of alveolar tissue, decline in alveolar tissue compliance and traction force-induced bronchial dilation. With these capabilities, we provide proof of principle for using this fibrotic tissue array for multi-parameter, phenotypic analysis of the therapeutic efficacy of two anti-fibrosis drugs recently approved by the FDA. Preventative treatments with Pirfenidone and Nintedanib reduce tissue contractility and prevent tissue stiffening and decline in tissue compliance. In a therapeutic treatment regimen, both drugs restore tissue compliance. These results highlight the pathophysiologically relevant modeling capability of our novel fibrotic microtissue system.