Publication Date
2023
Journal or Book Title
Advanced Healthcare Materials
Abstract
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.
ISSN
2192-2659
License
UMass Amherst Open Access Policy
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.
Recommended Citation
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.
Retrieved from https://scholarworks.umass.edu/che_faculty_pubs/922