ArticleACS biomaterials science & engineering2019
Spatial Regulation of Valve Interstitial Cell Phenotypes within Three-Dimensional Micropatterned Hydrogels.
Article in ACS biomaterials science & engineering, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 18 citations in OpenAlex.
- Construction of a Three-Dimensional Calcific Aortic Valve Disease Model Using Human iPSC-Derived Valvular Interstitial Cells.Stem cell reviews and reports · 2026Article
- Biomechanical Remodeling of Aortic Valve Interstitial Cells During Calcified Lesion Formation In Vitro.Annals of biomedical engineering · 2024Article
- Evolution of Hybrid Hydrogels: Next-Generation Biomaterials for Drug Delivery and Tissue Engineering.Gels (Basel, Switzerland) · 2024Review
- Models for calcific aortic valve disease in vivo and in vitro.Cell regeneration (London, England) · 2024Review
- Aortic valve cell microenvironment: Considerations for developing a valve-on-chip.Biophysics reviews · 2021Review
- The effects of surface topography modification on hydrogel properties.APL bioengineering · 2021Review
- Design and Development of Hybrid Hydrogels for Biomedical Applications: Recent Trends in Anticancer Drug Delivery and Tissue Engineering.Frontiers in bioengineering and biotechnology · 2021Review
- Age related extracellular matrix and interstitial cell phenotype in pulmonary valves.Scientific reports · 2020Article
- Hybrid hydrogels for biomedical applications.Current opinion in chemical engineering · 2019Article
- Extracellular Matrix Dynamics in Aortic Valve Health and Disease: Insights into Fibrocalcific Remodeling and Creation of Biomimetic Platforms.Journal of the Heart Valve SocietyArticle
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Calcific aortic valve disease (CAVD) is the third leading cause of cardiovascular disease. CAVD exhibits progressive disruption of the normally highly organized and aligned extracellular matrix (ECM) structure within the valve leaflets simultaneously with myofibroblastic and/or osteogenic differentiation of indigenous endogenous valve interstitial cells (VIC). It is unclear how the alignment of VIC within their 3D microenvironment drives VIC phenotype or how alignment affects cellular responses to biochemical cues in physiological or pathological conditions. In this study, we implement a photolithographic technique to control the alignment and elongation of both normal and diseased human aortic VIC (HAVIC) within microengineered 3D hydrogels consisting of methacrylated hyaluronic acid and methacrylated gelatin. Stripe micropatterning created distinct alignment of HAVIC within a 3D culture system, which promoted spreading and enhanced their activation and osteogenic differentiation in pro-osteogenic conditions. HAVIC from a patient with CAVD exhibited greater susceptibility to myofibroblastic and osteogenic differentiation in culture. The roles of conjugated basic fibroblastic growth factor (bFGF) and RhoA/ROCK pathway in regulating HAVIC phenotypes were also investigated in the presence of aligned microtopography. The addition of bFGF was preventative to osteogenic differentiation for healthy HAVIC; however, it promoted osteogenic differentiation in diseased HAVIC. Inhibition of the ROCK pathway only decreased osteogenic differentiation for diseased HAVIC in the aligned formation. Collectively, these results improve our knowledge of the effects that VIC alignment has on VIC phenotypes and valve disease progression. The cell culture platform also enables a better understanding of the interplay between topography, biochemical cues, and VIC differentiation and provides information useful for directing differentiation as well as valve tissue regeneration.
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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.