Microengineered 3D pulmonary interstitial mimetics highlight a critical role for matrix degradation in idiopathic pulmonary fibrosis

• DOI: 10.1101/2020.06.02.129718
• Publication Date: 2020-06-03T12:55:17Z
• Authors: Daniel L. Matera; Katarina M. DiLillo; Makenzee R. Smith; Christopher D. Da...; Ritika Parikh; Mohammed Said; Carole A. Wilke; Isabelle M. Lombaert; Kelly B. Arnold; Bethany B. Moore; Brendon M. Baker
• Keywords: Myofibroblast; Matrix (chemical analysis)

Abstract Fibrosis is often untreatable and characterized by aberrant tissue scarring from activated myofibroblasts. Although the extracellular matrix becomes increasingly stiff fibrous during disease progression, how these physical cues impact myofibroblast differentiation in 3D poorly understood. Here we describe a multicomponent hydrogel that recapitulates structure hallmark to interstitial regions where idiopathic pulmonary fibrosis (IPF) initiates. In contrast findings on 2D hydrogels, was inversely correlated with stiffness, but positively fiber density. Employing multi-step bioinformatics analysis of IPF patient transcriptomes vitro pharmacologic screening, identify matrix-metalloprotease activity be essential for not differentiation. Given our observation compliant degradable matrices amply support fibrogenesis, studies demonstrate departure established relationship between stiffness 2D, provide new model studying fibrosis.