Microfabricated polymeric vessel mimetics for 3-D cancer cell culture

  • Jaeger A
  • Das C
  • Morgan N
 et al. 
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Abstract

Modeling tumor growth invitro is essential for cost-effective testing of hypotheses in preclinical cancer research. 3-D cell culture offers an improvement over monolayer culture for studying cellular processes in cancer biology because of the preservation of cell-cell and cell-ECM interactions. Oxygen transport poses a major barrier to mimicking invivo environments and is not replicated in conventional cell culture systems. We hypothesized that we can better mimic the tumor microenvironment using a bioreactor system for controlling gas exchange in cancer cell cultures with silicone hydrogel synthetic vessels. Soft-lithography techniques were used to fabricate oxygen-permeable silicone hydrogel membranes containing arrays of micropillars. These membranes were inserted into a bioreactor and surrounded by basement membrane extract (BME) within which fluorescent ovarian cancer (OVCAR8) cells were cultured. Cell clusters oxygenated by synthetic vessels showed a ~100μm drop-off to anoxia, consistent with invivo studies of tumor nodules fed by the microvasculature. Oxygen transport in the bioreactor system was characterized by experimental testing with a dissolved oxygen probe and finite element modeling of convective flow. Our study demonstrates differing growth patterns associated with controlling gas distributions to better mimic invivo conditions. © 2013 .

Author-supplied keywords

  • Bioreactor
  • Carcinogenesis
  • Hydrogel
  • Microstructure
  • Oxygenation
  • Silicone

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Authors

  • Ashley A. Jaeger

  • Chandan K. Das

  • Nicole Y. Morgan

  • Randall H. Pursley

  • Philip G. McQueen

  • Matthew D. Hall

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