Mimicking Embedded Vasculature Structure for 3D Cancer on a Chip Approaches through Micromilling
Open accessAbstract
The ability for cells to sense and respond to microenvironmental signals is influenced by their three dimensional (3D) surroundings, which includes the extracellular matrix (ECM). In the 3D environment, vascular structures supply cells with nutrients and oxygen thus affecting cell responses such as motility. Interpretation of cell motility studies though is often restricted by the applied approaches such as 2D conventional soft lithography methods that have rectangular channel cross-sectional morphology. To better simulate cell responses to vascular supply in 3D, we developed a cell on a chip system with microfluidic channels with curved cross-sections embedded within a 3D collagen matrix that emulates anatomical vasculature more closely than inorganic polymers, thus to mimic a more physiologically relevant 3D cellular environment. To accomplish this, we constructed perfusable microfluidic channels by embedding sacrificial circular gelatin vascular templates in collagen, which were removed through temperature control. Motile breast cancer cells were pre-seeded into the collagen matrix and when presented with a controlled chemical stimulation from the artificial vasculature, they migrated towards the vasculature structure. We believe this innovative vascular 3D ECM system can be used to provide novel insights into cellular dynamics during multidirectional chemokineses and chemotaxis that exist in cancer and other diseases.
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Through precise microfluidic designs, microfluidic devices can reconstruct physiological dynamic characteristics in tissues, such as physiological flow, shear stress, nutrient delivery, and drug action, in a controllable environment.
“Through precise microfluidic designs, microfluidic devices can reconstruct physiological dynamic characteristics in tissues, such as physiological flow, shear stress, nutrient delivery, and drug action, in a controllable environment, providing a platform for cell culture, microenvironment creation, and organ simulation or in vitro assessment of organ tissue60–67.”
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- Authors
- Wan, L., Skoko, J., Yu, J., Ozdoganlar, O. B., LeDuc, P. R., & Neumann, C. A.
- Affiliations
- Carnegie Mellon University (US)
- Magee-Womens Research Institute (US)
- Corresponding author
- LeDuc, P. R.
- Neumann, C. A.
- Venue
- Scientific Reports
- Published
- 2017-12-01
- Volume
- 7
- Issue
- 1
- Pages
- 16724-16724
- ISSN
- 2045-2322 (ISSN-L)
- PMC
- PMC5711800
- OpenAlex
- W2770077816
- Cited by
- 38
- References
- 45
- Citations by year
- 2024: 8 · 2023: 5 · 2022: 4 · 2021: 8 · 2020: 7 · 2019: 4 · 2018: 2
- FWCI
- 1.60
- Type
- journal article
- Language
- en
- Update notices
- correction (2019-03-28)
- Open access
- gold
- doi.org
- Locations
- Scientific Reports (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Funders
- National Science Foundation (N00014-17-1-2566, 1547810)
- Cotswold Foundation
- National Institutes of Health
- Office of Naval Research (N00014-17-1-2566, N00014-17-1, CBET-1547810, FA9550, N00014)
- National Cancer Institute (R01CA131350)
- Division of Chemical, Bioengineering, Environmental, and Transport Systems (CBET-1547810)
- Air Force Office of Scientific Research (FA9550-, FA9550-13-1-01 08)
- Topics
- Physical Sciences › Engineering › Biomedical Engineering › 3D Printing in Biomedical Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
- Physical Sciences › Engineering › Biomedical Engineering › Microfluidic and Capillary Electrophoresis Applications
- Keywords
- micro-milling, collagen matrix, microfluidic channels, chemotaxis, chemokines, extracellular matrix, cell microenvironment
- MeSH terms
- Breast Neoplasms, Cell Movement, Cross-Sectional Studies, Extracellular Matrix, Female, Humans, Cell Culture Techniques, Tissue Engineering, Cell Line, Tumor, Microfluidic Analytical Techniques
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