Pulmonary fibrotic microtissue array for screening anti-fibrosis therapy

Statement of Purpose: Idiopathic pulmonary fibrosis, characterized by the progressive stiffening of lung’s soft tissue, leads to organ failure and currently has no cure. Anti-fibrosis drug development is significantly limited by the long duration and high cost of clinical trials. Pre-clinical models that can recapitulate sophisticated biomechanical environment of lung tissue and provide early efficacy of the drugs are highly desired. 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 [1]. We then integrate fibrotic microtissue array with a cyclic stretching system to mimic respiration motion. Finally, 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.