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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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Available for download on Friday, November 15, 2024