Microengineered 3D pulmonary interstitial mimetics highlight a critical role for matrix degradation in myofibroblast differentiation.

Fibrosis, characterized by aberrant tissue scarring from activated myofibroblasts, is often untreatable. Although the extracellular matrix becomes increasingly stiff and fibrous during disease progression, how these physical cues affect myofibroblast differentiation in 3D is poorly understood. Here, we describe a multicomponent hydrogel that recapitulates the 3D fibrous structure of interstitial tissue regions where idiopathic pulmonary fibrosis (IPF) initiates.

Fiber Density Modulates Cell Spreading in 3D Interstitial Matrix Mimetics.

Cellular phenotype is heavily influenced by the extracellular matrix (ECM), a complex and tissue-specific three-dimensional structure with distinct biophysical and biochemical properties. As naturally derived cell culture platforms are difficult to controllably modulate, engineered synthetic ECMs have facilitated our understanding of how specific matrix properties direct cell behavior. However, synthetic approaches typically lack fibrous topography, a hallmark of stromal and interstitial ECMs in vivo.