Microfabricated polymeric vessel mimetics for 3-D cancer cell culture

Biomaterials. 2013 Nov;34(33):8301-13. doi: 10.1016/j.biomaterials.2013.07.013. Epub 2013 Jul 30.


Modeling tumor growth in vitro 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 in vivo 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 in vivo 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 in vivo conditions.

Keywords: Bioreactor; Carcinogenesis; Hydrogel; Microstructure; Oxygenation; Silicone.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Bioreactors
  • Cell Culture Techniques / methods*
  • Cell Line, Tumor
  • Female
  • Humans
  • Microtechnology*
  • Polymers / chemistry*


  • Polymers