Journal or Book Title
Advanced Healthcare Materials
The lung extracellular matrix (ECM) maintains the structural integrity of the tissue and regulates the phenotype and functions of resident fibroblasts. Lung-metastatic breast cancer alters these cell-ECM interactions, promoting fibroblast activation. There is a need for bio-instructive ECM models that contain the ECM composition and biomechanics of the lung to study these cell-matrix interactions in vitro. Here, we developed a synthetic, bioactive hydrogel that mimics the native lung modulus and includes a representative distribution of the most abundant ECM peptide motifs responsible for integrin binding and matrix metalloproteinase (MMP)-mediated degradation in the lung, which enables quiescent culture of human lung fibroblasts (HLFs). Stimulation with transforming growth factor β1 (TGF-β1), metastatic breast cancer conditioned media (CM), or tenascin-C-derived integrin-binding peptide activated hydrogel-encapsulated HLFs, demonstrating multiple environmental methods to activate HLFs in a lung ECM mimicking hydrogel. We propose this lung hydrogel platform as a tunable, synthetic approach to studying the independent and combinatorial effects of ECM in regulating fibroblast quiescence and activation.
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Kundu, Aritra; Dougan, Carey; Mahmoud, Samar; Panagiotou, Alexi; Richbourg, Nathan; Irakoze, Ninette; and Peyton, Shelly, "Tenascin-C activation of lung fibroblasts in a 3D synthetic lung extracellular matrix mimic" (2023). Advanced Healthcare Materials. 922.
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