Microfabricated Fibrotic Microtissue Array for Screening of Potential Anti-Fibrotic Treatments
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Fibrosis is a severe disease characterized by excessive accumulation of extracellular matrix and stiffening of the tissue during wound healing. It often leads to organ failure and has a high mortality rate. Development of new anti-fibrosis therapies is a highly inefficient process, as no existing in vitro models can accurately recapitulate the dynamic patho-physiological changes in tissue mechanics during fibrogenesis. In this study, we created novel micropillar microdevices, which allow thin and membranous fibroblast microtissues to be formed, similar to the morphology of lung alveolar tissue. We show the capability of these devices to replicate the fibrogenesis process, by using TGF-β1 to induce compliant lung microtissues into a rigid and contractile condition that matches that of interstitial lung fibrosis. Two drugs in phase II clinical trial for idiopathic pulmonary fibrosis, which have been shown to potentially possess anti-fibrotic properties, are used to treat the fibrotic microtissues. Both drugs provided significant reduction in contraction forces, ECM production, and stiffness of the fibrotic tissues. The results indicate that these microdevices can model the dynamic process of fibrogenesis on a multiscale level and is therefore an excellent platform for screening potential anti-fibrotic drugs.