Three-dimensional microfluidic collagen hydrogels for investigating flow-mediated tumor-endothelial signaling and vascular organization
Open accessAbstract
Hyperpermeable tumor vessels are responsible for elevated interstitial fluid pressure and altered flow patterns within the tumor microenvironment. These aberrant hydrodynamic stresses may enhance tumor development by stimulating the angiogenic activity of endothelial cells lining the tumor vasculature. However, it is currently not known to what extent shear forces affect endothelial organization or paracrine signaling during tumor angiogenesis. The objective of this study was to develop a three-dimensional (3D), in vitro microfluidic tumor vascular model for coculture of tumor and endothelial cells under varying flow shear stress conditions. A central microchannel embedded within a collagen hydrogel functions as a single neovessel through which tumor-relevant hydrodynamic stresses are introduced and quantified using microparticle image velocimetry (μ-PIV). This is the first use of μ-PIV in a tumor representative, 3D collagen matrix comprised of cylindrical microchannels, rather than planar geometries, to experimentally measure flow velocity and shear stress. Results demonstrate that endothelial cells develop a confluent endothelium on the microchannel lumen that maintains integrity under physiological flow shear stresses. Furthermore, this system provides downstream molecular analysis capability, as demonstrated by quantitative RT-PCR, in which, tumor cells significantly increase expression of proangiogenic genes in response to coculture with endothelial cells under low flow conditions. This work demonstrates that the microfluidic in vitro cell culture model can withstand a range of physiological flow rates and permit quantitative measurement of wall shear stress at the fluid-collagen interface using μ-PIV optical flow diagnostics, ultimately serving as a versatile platform for elucidating the role of fluid forces on tumor-endothelial cross talk.
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Microfluidic platforms have been developed that integrate spheroid cultures with controlled flow.
“microfluidic platforms have been developed that integrate spheroid cultures with controlled flow [49,223].”
From Modeling Tumor Microenvironment Complexity In Vitro: Spheroids as Physiologically Relevant Tumor Models and Strategies for Their Analysis (2025) · cites this paper as [223]
The Results (page not provided) describe a microfluidic collagen hydrogel with controlled flow and tumor cells seeded in the bulk of the hydrogel. This supports the controlled-flow platform, but the paper does not describe integrating spheroid cultures; its model uses tumor–endothelial cell coculture instead. (LLM, conf=0.89)
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Self-citation
- Authors
- Buchanan, C. F., Voigt, E. E., Szot, C. S., Freeman, J. W., Vlachos, P. P., & Rylander, M. N.
- Affiliations
- Virginia Tech - Wake Forest University School of Biomedical Engineering & Sciences (US)
- Department of Mechanical Engineering, Virginia Tech, Blacksburg, Virginia.
- Rutgers, The State University of New Jersey (US)
- Corresponding author
- Buchanan, Cara F.
- Venue
- Tissue Engineering Part C: Methods
- Publisher
- SAGE Publications
- Published
- 2014-01
- Volume
- 20
- Issue
- 1
- Pages
- 64-75
- ISSN
- 1937-3384 (ISSN-L)
- 1937-3392
- PMC
- PMC3870485
- OpenAlex
- W2075280869
- Cited by
- 143
- References
- 82
- Citations by year
- 2026: 7 · 2025: 5 · 2024: 7 · 2023: 6 · 2022: 14 · 2021: 14 · 2020: 13 · 2019: 11 · 2018: 15 · 2017: 13 · 2016: 12 · 2015: 12 · 2014: 11 · 2013: 3
- FWCI
- 6.99
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Tissue Engineering Part C Methods (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Science Foundation (0955072, CAREER)
- National Cancer Institute (IR21CA158454-01A1)
- Division of Chemical, Bioengineering, Environmental, and Transport Systems
- Topics
- Physical Sciences › Engineering › Biomedical Engineering › 3D Printing in Biomedical Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Angiogenesis and VEGF in Cancer
- Keywords
- tumor angiogenesis, endothelial cells, shear stress, wall shear stress, collagen gel, tumor microenvironment, paracrine signaling, micro-PIV
- MeSH terms
- Animals, Cell Survival, Collagen, Neoplasms, Refractometry, Rheology, Signal Transduction, Gene Expression Regulation, Neoplastic, Coculture Techniques, Hydrogels, Endothelial Cells, Cell Line, Tumor, Microfluidic Analytical Techniques, Cell Proliferation, Rats
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