archives@tulane.edu / Fibrotic diseases comprise up to 45% of deaths in the industrialized world. Few effective anti-fibrotic therapeutics exist, due in part to the lack of human-relevant preclinical models. The goal of this research was to improve the modeling of fibrotic diseases in microphysiological systems (MPS) by engineering quiescence in cultured human fibroblasts prior to MPS incorporation. To create an assay for testing this approach, a versatile organ chip was designed while optimizing workflow for production of the organ chip molds with an SLA 3D printer. After identifying 2D culture conditions that repress fibroblast activation, we tested the hypothesis that the 2D culture protocol would impact the fibrotic baseline in our MPS. 3D confocal microscopy and multi-metric image analysis of immunostaining for cellular and extracellular matrix (ECM) components via intensity and pattern quantification revealed the establishment of more physiological baseline for MPS fibrosis models. To test in a disease-relevant context, we created a model of the stromal reaction in lung cancer using our organ chip and demonstrated that our integrated MPS can be used to quantify the fibrosis-inducing effects of cancer cells that drive stromal reactions. / 1 / Max Wendell