ArticleActa biomaterialia2012
Cyclic strain anisotropy regulates valvular interstitial cell phenotype and tissue remodeling in three-dimensional culture.
Article in Acta biomaterialia, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers.
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Who cites it
55 citing papers in PubMed, 119 citations in OpenAlex.
- From biomechanical mechanisms to clinical reasoning: Deciphering mechanobiological drivers of aortic valve calcification for precision therapy.Mechanobiology in medicine · 2026Review
- Functional hydrogels in cardiovascular therapy: Design, applications and clinical challenges (Review).International journal of molecular medicine · 2026Review
- Restoration of structural organization in engineered cardiac microtissues is promoted by cardiomyocyte beating.Communications biology · 2026Article
- The interaction between sarcoplasmic reticulum and mitochondria: a novel mechanism for cardiac arrhythmia.Frontiers in physiology · 2026Review
- Digital light processing of hydrogel molds to guide cell mechanosensing and the fabrication of meniscal tissue constructs.APL bioengineering · 2025Article
- A multimodal microfluidic-based platform integrating topographical and equibiaxial mechanical cues for next-generationFrontiers in bioengineering and biotechnology · 2025Article
- Models for calcific aortic valve disease in vivo and in vitro.Cell regeneration (London, England) · 2024Review
- Self-organizing behaviors of cardiovascular cells on synthetic nanofiber scaffolds.APL bioengineering · 2023Article
- Strategies for Development of Synthetic Heart Valve Tissue Engineering Scaffolds.Progress in materials science · 2023Article
- The effects of strain history on aortic valve interstitial cell activation in a 3D hydrogel environment.APL bioengineering · 2023Article
- Design of a Mechanobioreactor to Apply Anisotropic, Biaxial Strain to Large Thin Biomaterials for Tissue Engineered Heart Valve Applications.Annals of biomedical engineering · 2022Article
- Engineering the aortic valve extracellular matrix through stages of development, aging, and disease.Journal of molecular and cellular cardiology · 2021Review
- Aortic valve cell microenvironment: Considerations for developing a valve-on-chip.Biophysics reviews · 2021Review
- How Do Mechanics Guide Fibroblast Activity? Complex Disruptions during Emphysema Shape Cellular Responses and Limit Research.Bioengineering (Basel, Switzerland) · 2021Review
- Degeneration of Aortic Valves in a Bioreactor System with Pulsatile Flow.Biomedicines · 2021Article
- Notch in mechanotransduction - from molecular mechanosensitivity to tissue mechanostasis.Journal of cell science · 2020Review
- TENSCell: Imaging of Stretch-Activated Cells Reveals Divergent Nuclear Behavior and Tension.Biophysical journal · 2020Article
- Engineering Biomaterials and Approaches for Mechanical Stretching of Cells in Three Dimensions.Frontiers in bioengineering and biotechnology · 2020Review
- Repeated In Vitro Impact Conditioning of Astrocytes Decreases the Expression and Accumulation of Extracellular Matrix.Annals of biomedical engineering · 2019Article
- Spatial Regulation of Valve Interstitial Cell Phenotypes within Three-Dimensional Micropatterned Hydrogels.ACS biomaterials science & engineering · 2019Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Many planar connective tissues exhibit complex anisotropic matrix fiber arrangements that are critical to their biomechanical function. This organized structure is created and modified by resident fibroblasts in response to mechanical forces in their environment. The directionality of applied strain fields changes dramatically during development, aging, and disease, but the specific effect of strain direction on matrix remodeling is less clear. Current mechanobiological inquiry of planar tissues is limited to equibiaxial or uniaxial stretch, which inadequately simulates many in vivo environments. In this study, we implement a novel bioreactor system to demonstrate the unique effect of controlled anisotropic strain on fibroblast behavior in three-dimensional (3-D) engineered tissue environments, using aortic valve interstitial fibroblast cells as a model system. Cell seeded 3-D collagen hydrogels were subjected to cyclic anisotropic strain profiles maintained at constant areal strain magnitude for up to 96 h at 1 Hz. Increasing anisotropy of biaxial strain resulted in increased cellular orientation and collagen fiber alignment along the principal directions of strain and cell orientation was found to precede fiber reorganization. Cellular proliferation and apoptosis were both significantly enhanced under increasing biaxial strain anisotropy (P<0.05). While cyclic strain reduced both vimentin and alpha-smooth muscle actin compared to unstrained controls, vimentin and alpha-smooth muscle actin expression increased with strain anisotropy and correlated with direction (P<0.05). Collectively, these results suggest that strain field anisotropy is an independent regulator of fibroblast cell phenotype, turnover, and matrix reorganization, which may inform normal and pathological remodeling in soft tissues.
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Registered trials
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