ArticleBiomaterials2015
Dynamic stiffening of poly(ethylene glycol)-based hydrogels to direct valvular interstitial cell phenotype in a three-dimensional environment.
Article in Biomaterials, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 115 papers.
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Who cites it
115 citing papers in PubMed, 215 citations in OpenAlex.
- Aortic valve stenosis serum IGFBP2 mediates female-specific Evogliptin resistance in valve myofibroblasts.Cell reports · 2026Article
- Ancestry-linked IL-10 signaling and macrophage activation modulate fibroblast responses to oxidative stress in a PEG-based microphysiological system.npj biomedical innovations · 2026Article
- Hydrogel-Embedded Precision-Cut Lung Slices Recapitulate Fibrotic Gene Expression and Enable Therapeutic Response Evaluation.bioRxiv : the preprint server for biology · 2026Article
- Cell-Laden Supramolecular and Covalent Polymer Hydrogels for High-Shear Delivery: A Design of Experiments Approach.Chemistry of materials : a publication of the American Chemical Society · 2026Article
- Effects of Stiffness and Degradability on Cardiac Fibroblast Contractility and Extracellular Matrix Secretion in Three-Dimensional Hydrogel Scaffolds.ACS biomaterials science & engineering · 2025Article
- Revisiting the biophysical aspects of extracellular-matrix-mimicking hydrogels: what cells seeBiomaterials science · 2025Review
- Interpenetrating Polymer Network Hydrogel Composition Alters Encapsulated MSC Spreading and In Vivo Degradation Behavior.ACS biomaterials science & engineering · 2025Article
- Determining sex differences in aortic valve myofibroblast responses to drug combinations identified using a digital medicine platform.Science advances · 2025Article
- Full-Field Assessment of Geometry and Collagenous Architecture of Porcine Valve Leaflets via Laser Micrometry and Quantitative Polarized Light Imaging.Journal of biophotonics · 2025Article
- Secreted Cytokines From Inflammatory Macrophages Modulate Sex Differences in Valvular Interstitial Cells on Hydrogel Biomaterials.Journal of biomedical materials research. Part A · 2025Article
- Light-based fabrication and 4D customization of hydrogel biomaterials.Nature reviews bioengineering · 2025Article
- Evolving functional hydrogel strategies for cartilage engineering: from fundamentals to functional regeneration.Burns & trauma · 2025Review
- Insights into preclinical models of calcific aortic valve disease and their translational potential.Frontiers in cardiovascular medicine · 2025Review
- Binary fabrication of decellularized lung extracellular matrix hybridgels for in vitro chronic obstructive pulmonary disease modeling.Acta biomaterialia · 2024Article
- Harnessing the potential of hydrogels for advanced therapeutic applications: current achievements and future directions.Signal transduction and targeted therapy · 2024Review
- Enhanced osteogenesis of mesenchymal stem cells encapsulated in injectable microporous hydrogel.Scientific reports · 2024Article
- Multiscale embedded printing of engineered human tissue and organ equivalents.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Substrate stiffness modulates cardiac fibroblast activation, senescence, and proinflammatory secretory phenotype.American journal of physiology. Heart and circulatory physiology · 2024Article
- Serial Passaging Affects Stromal Cell Mechanosensitivity on Hyaluronic Acid Hydrogels.Macromolecular bioscience · 2024Article
- The Role of Apoptosis and Oxidative Stress in a Cell Spheroid Model of Calcific Aortic Valve Disease.Cells · 2023Article
55 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
Valvular interstitial cells (VICs) are active regulators of valve homeostasis and disease, responsible for secreting and remodeling the valve tissue matrix. As a result of VIC activity, the valve modulus can substantially change during development, injury and repair, and disease progression. While two-dimensional biomaterial substrates have been used to study mechanosensing and its influence on VIC phenotype, less is known about how these cells respond to matrix modulus in a three-dimensional environment. Here, we synthesized MMP-degradable poly(ethylene glycol) (PEG) hydrogels with elastic moduli ranging from 0.24 kPa to 12 kPa and observed that cell morphology was constrained in stiffer gels. To vary gel stiffness without substantially changing cell morphology, cell-laden hydrogels were cultured in the 0.24 kPa gels for 3 days to allow VIC spreading, and then stiffened in situ via a second, photoinitiated thiol-ene polymerization such that the gel modulus increased from 0.24 kPa to 1.2 kPa or 13 kPa. VICs encapsulated within soft gels exhibited αSMA stress fibers (∼ 40%), a hallmark of the myofibroblast phenotype. Interestingly, in stiffened gels, VICs became deactivated to a quiescent fibroblast phenotype, suggesting that matrix stiffness directs VIC phenotype independent of morphology, but in a manner that depends on the dimensionality of the culture platform. Collectively, these studies present a versatile method for dynamic stiffening of hydrogels and demonstrate the significant effects of matrix modulus on VIC myofibroblast properties in three-dimensional environments.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.