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 match the ECM composition and biomechanics of the lung to study these cell‐matrix interactions in vitro. Here, a synthetic, bioactive hydrogel is synthesized 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 demonstrates multiple environmental methods to activate HLFs in a lung ECM‐mimicking hydrogel. This lung hydrogel platform is a tunable, synthetic approach to studying the independent and combinatorial effects of ECM in regulating fibroblast quiescence and activation.
Bioengineers have designed numerous instructive brain extracellular matrix (ECM) environments with tailored and tunable protein compositions and biomechanical properties in vitro to study astrocyte reactivity during trauma and inflammation. However, a major limitation of both protein‐based and synthetic model microenvironments is that astrocytes within fail to retain their characteristic stellate morphology and quiescent state without becoming activated under “normal” culture conditions. Here, a synthetic hydrogel is introduced, which for the first time demonstrates maintenance of astrocyte quiescence and activation on demand. With this synthetic brain hydrogel, the brain‐specific integrin‐binding and matrix metalloprotease‐degradable domains of proteins are shown to control astrocyte star‐shaped morphologies, and an ECM condition that maintains astrocyte quiescence with minimal activation can be achieved. In addition, activation can be induced in a dose‐dependent manner via both defined cytokine cocktails and low molecular weight hyaluronic acid. This synthetic brain hydrogel is envisioned as a new tool to study the physiological role of astrocytes in health and disease.
more » « less- Award ID(s):
- 1454806
- NSF-PAR ID:
- 10457830
- Publisher / Repository:
- Wiley Blackwell (John Wiley & Sons)
- Date Published:
- Journal Name:
- Advanced Healthcare Materials
- Volume:
- 9
- Issue:
- 4
- ISSN:
- 2192-2640
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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