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A microfabricated platform for establishing oxygen gradients in 3-D constructs

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Abstract

Oxygen gradients are increasingly implicated in a number of biological processes, including stem cell differentiation and cancer metastasis. Unfortunately, the current in vitro tools designed to mimic conditions found in vivo lack application flexibility, simplicity in operation, and precise spatial control that most researchers require for widespread dissemination. The novel microfluidic-based device presented here addresses all the above concerns, offering a simple platform for enhanced control over the oxygen microenvironment exposed to three-dimensional cell-seeded constructs. The device utilizes an oxygen diffusion membrane approach to establish a gradient across a construct sandwiched between two continually perfused microfluidic networks. The device is capable of forming steady-state gradients at both the conditions tested—0 % to 5 % O2 and 0 % to 21 % O2—but a wide variety of profiles within the construct are possible. Cell viability with two model cell lines was also tested, with no adverse effects relative to the control.

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References

  • M. Adler, M. Polinkovsky, E. Gutierrez, A. Groisman, Lab. Chip. 10, 388–391 (2010)

    Article  Google Scholar 

  • J.W. Allen, S.N. Bhatia, Biotechnol. Bioeng. 82, 253–262 (2003)

    Article  Google Scholar 

  • J.W. Allen, R.S. Johnson, S.N. Bhatia, Hepatology 38, 270a–270a (2003)

    Article  Google Scholar 

  • M.E. Alvarez, R.I. Pennell, P.J. Meijer, A. Ishikawa, R.A. Dixon, C. Lamb, Cell 92, 773–784 (1998)

    Article  Google Scholar 

  • P. Baluk, S. Morikawa, A. Haskell, M. Mancuso, D.M. McDonald, Am. J. Pathol. 163, 1801–1815 (2003)

    Article  Google Scholar 

  • K.L. Bennewith, R.E. Durand, Cancer Res. 64, 6183–6189 (2004)

    Article  Google Scholar 

  • K.G. Brurberg, B.A. Graff, E.K. Rofstad, Br. J. Cancer 89, 350–356 (2003)

    Article  Google Scholar 

  • K.G. Brurberg, M. Thuen, E.B. Ruud, E.K. Rofstad, Radiat. Res. 165, 16–25 (2006)

    Article  Google Scholar 

  • P. Carmeliet, Y. Dor, J.M. Herbert, D. Fukumura, K. Brusselmans, M. Dewerchin, M. Neeman, F. Bono, R. Abramovitch, P. Maxwell, C.J. Koch, P. Ratcliffe, L. Moons, R.K. Jain, D. Collen, E. Keshert, Nature 394, 485–490 (1998)

    Article  Google Scholar 

  • C.C. Ceresa, A.J. Knox, S.R. Johnson, Am. J. Physiol. Lung. Cell. Mol. Physiol. 296, L1059–1066 (2009)

    Article  Google Scholar 

  • G. Chamberlain, J. Fox, B. Ashton, J. Middleton, Stem Cells 25, 2739–2749 (2007)

    Article  Google Scholar 

  • D.A. Chan, A.J. Giaccia, Cancer Metastasis Rev. 26, 333–339 (2007)

    Article  Google Scholar 

  • C. Chen, K. Chen, S.T. Yang, Biotechnol. Prog. 19, 1574–1582 (2003)

    Article  Google Scholar 

  • N.W. Choi, M. Cabodi, B. Held, J.P. Gleghorn, L.J. Bonassar, A.D. Stroock, Nat. Mater. 6, 908–915 (2007)

    Article  Google Scholar 

  • M.C. Drew, Ann. Rev. Plant Physiol. Plant Mol. Biol. 48, 223–250 (1997)

    Article  Google Scholar 

  • X. Fan, R. Zou, Z. Zhao, P. Yang, Y. Li, J. Song, Tissue Cell 41, 266–270 (2009)

    Article  Google Scholar 

  • W.L. Grayson, F. Zhao, R. Izadpanah, B. Bunnell, T. Ma, J. Cell. Physiol. 207, 331–339 (2006)

    Article  Google Scholar 

  • G. Helmlinger, F. Yuan, M. Dellian, R.K. Jain, Nat. Med. 3, 177–182 (1997)

    Article  Google Scholar 

  • C. Holzer, P. Maier, J. Cell. Physiol. 133, 297–304 (1987)

    Article  Google Scholar 

  • H. Hosseinkhani, M. Hosseinkhani, H. Kobayashi, J. Bioact. Compat. Polym. 21, 277–296 (2006)

    Article  Google Scholar 

  • S.S. Kim, H. Utsunomiya, J.A. Koski, B.M. Wu, M.J. Cima, J. Sohn, K. Mukai, L.G. Griffith, J.P. Vacanti, Ann. Surg. 228, 8–13 (1998)

    Article  Google Scholar 

  • M. Kucia, R. Reca, K. Miekus, J. Wanzeck, W. Wojakowski, A. Janowska-Wieczorek, J. Ratajczak, M.Z. Ratajczak, Stem Cells 23, 879–894 (2005)

    Article  Google Scholar 

  • J. Lanzen, R.D. Braun, B. Klitzman, D. Brizel, T.W. Secomb, M.W. Dewhirst, Cancer Res. 66, 2219–2223 (2006)

    Article  Google Scholar 

  • D.P. Lennon, J.M. Edmison, A.I. Caplan, J. Cell. Physiol. 187, 345–355 (2001)

    Article  Google Scholar 

  • G.N. Li, L.L. Livi, C.M. Gourd, E.S. Deweerd, D. Hoffman-Kim, Tissue Eng. 13, 1035–1047 (2007)

    Article  Google Scholar 

  • M. Lovett, D. Rockwood, A. Baryshyan, D.L. Kaplan, Tissue Eng. Part C Methods 16, 1565–1573 (2010)

    Article  Google Scholar 

  • T. Luhmann, P. Hanseler, B. Grant, H. Hall, Biomaterials 30, 4503–4512 (2009)

    Article  Google Scholar 

  • G. Mehta, K. Mehta, D. Sud, J.W. Song, T. Bersano-Begey, N. Futai, Y.S. Heo, M.A. Mycek, J.J. Linderman, S. Takayama, Biomed. Microdevices 9, 123–134 (2007)

    Article  Google Scholar 

  • T. Nakamura, Y. Kato, H. Fujii, T. Horiuchi, Y. Chiba, K. Tanaka, Int. J. Mol. Med. 12, 693–700 (2003)

    Google Scholar 

  • S.C. Oppegard, E. Sinkala, D. Eddington, J. Vis. Exp., (2010a)

  • S.C. Oppegard, A.J. Blake, J.C. Williams, D.T. Eddington, Lab. Chip. 10, 2366–2373 (2010b)

    Article  Google Scholar 

  • S.C. Oppegard, K.H. Nam, J.R. Carr, S.C. Skaalure, D.T. Eddington, PLoS One 4, e6891 (2009)

    Article  Google Scholar 

  • K. Parmar, P. Mauch, J.A. Vergilio, R. Sackstein, J.D. Down, P. Natl. Acad. Sci. USA 104, 5431–5436 (2007)

    Article  Google Scholar 

  • S.R. Peyton, P.D. Kim, C.M. Ghajar, D. Seliktar, A.J. Putnam, Biomaterials 29, 2597–2607 (2008)

    Article  Google Scholar 

  • S.R. Peyton, C.B. Raub, V.P. Keschrumrus, A.J. Putnam, Biomaterials 27, 4881–4893 (2006)

    Article  Google Scholar 

  • M.F. Pittenger, A.M. Mackay, S.C. Beck, R.K. Jaiswal, R. Douglas, J.D. Mosca, M.A. Moorman, D.W. Simonetti, S. Craig, D.R. Marshak, Science 284, 143–147 (1999)

    Article  Google Scholar 

  • E.K. Rofstad, Int. J. Radiat. Biol. 76, 589–605 (2000)

    Article  Google Scholar 

  • E.K. Rofstad, T. Danielsen, Br. J. Cancer 77, 897–902 (1998)

    Article  Google Scholar 

  • E.K. Rofstad, T. Danielsen, Br. J. Cancer 80, 1697–1707 (1999)

    Article  Google Scholar 

  • A. Salim, A.J. Giaccia, M.T. Longaker, Nat. Biotechnol. 22, 804–05 (2004). author reply 805-806

    Article  Google Scholar 

  • G.L. Semenza, Genes Dev. 14, 1983–1991 (2000)

    Google Scholar 

  • G.L. Semenza, Science 318, 62–64 (2007)

    Article  Google Scholar 

  • G.L. Semenza, Annu. Rev. Cell Dev. Biol. 15, 551–578 (1999)

    Article  Google Scholar 

  • G.L. Semenza, Biochem. Pharmacol. 64, 993–998 (2002)

    Article  Google Scholar 

  • C.C. Solorzano, C.H. Baker, C.J. Bruns, J.J. Killion, L.M. Ellis, J. Wood, I.J. Fidler, Cancer Biother. Radiopharm. 16, 359–370 (2001)

    Article  Google Scholar 

  • R. Sullivan, C.H. Graham, Cancer Metastasis Rev. 26, 319–331 (2007)

    Article  Google Scholar 

  • P.C. Thomas, S.R. Raghavan, S.P. Forry, Anal. Chem., (2011)

  • S.S. Verbridge, N.W. Choi, Y. Zheng, D.J. Brooks, A.D. Stroock, C. Fischbach, Tissue Eng. Part A 16, 2133–2141 (2010)

    Article  Google Scholar 

  • A.P. Vollmer, R.F. Probstein, R. Gilbert, T. Thorsen, Lab. Chip. 5, 1059–1066 (2005)

    Article  Google Scholar 

  • G.L. Wang, B.H. Jiang, E.A. Rue, G.L. Semenza, P. Natl. Acad. Sci. USA 92, 5510–5514 (1995)

    Article  Google Scholar 

  • G.M. Whitesides, E. Ostuni, S. Takayama, X. Jiang, D.E. Ingber, Annu. Rev. Biomed. Eng. 3, 335–373 (2001)

    Article  Google Scholar 

  • M.A. Wozniak, K. Modzelewska, L. Kwong, P.J. Keely, Biochim. Biophys. Acta (BBA) - Mol. Cell Res. 1692, 103–119 (2004)

    Article  Google Scholar 

  • J. Zhang, A. Skardal, G.D. Prestwich, Biomaterials 29, 4521–4531 (2008)

    Article  Google Scholar 

  • X.L. Zhang, Y.B. Xie, C.G. Koh, L.J. Lee, Biomed. Microdevices 4, 795–799 (2009)

    Article  Google Scholar 

Download references

Acknowledgments

This work was supported by NSF 0852416, NIH U54 CA151880, and the Chicago Biomedical Consortium with support from the Searle Funds at The Chicago Community Trust.

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Authors and Affiliations

  1. Department of Bioengineering, University of Illinois at Chicago, Chicago, IL, USA

    Shawn C. Oppegard & David T. Eddington

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  1. Shawn C. Oppegard
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  2. David T. Eddington
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Correspondence to David T. Eddington.

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Oppegard, S.C., Eddington, D.T. A microfabricated platform for establishing oxygen gradients in 3-D constructs. Biomed Microdevices 15, 407–414 (2013). https://doi.org/10.1007/s10544-013-9737-0

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