Skip to main content
Log in

Two-dimensional microarray of HepG2 spheroids using collagen/polyethylene glycol micropatterned chip

  • Published:
Journal of Materials Science: Materials in Medicine Aims and scope Submit manuscript

Abstract

A new cell chip technology in the form of a two-dimensional microarray of HepG2 spheroids was developed by using the microcontact printing technique. The chip consisted of several collagen spots in a triangular arrangement within a 100-mm2 area at the center of a glass plate (24 × 24 mm), which served as the cell adhesion area; the region excluding the collagen spots that was modified with polyethylene glycol (PEG) served as the non-adhesion area. HepG2 cells inoculated onto the chip gradually formed spheroids with smooth surfaces and high circularity on each collagen spot due to cell proliferation; the spheroid diameters remained constant after 10 days of culture. Such a two-dimensional microarray configuration of HepG2 spheroids could be maintained for at least 2 weeks. The spheroid diameter was directly proportional to the pitch between the collagen spots on the chip. This indicates that we can factitiously control the spheroid diameter. In addition, albumin secretion activity of HepG2 spheroids increased with the increase of spheroid diameter. This chip technology may be applicable as a cellular platform for developing two-dimensional spheroid microarrays.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9

Similar content being viewed by others

References

  1. J. ZIAUDDIN and D. M. SABATINI, Nature 411 (2001) 107

    Article  CAS  Google Scholar 

  2. J. P. STEPHAN, S. SCHANZ, A. WONG, P. SCHOW and W. L. T. WONG, Am. J. Pathol. 161 (2002) 787

    Google Scholar 

  3. C. J. FLAIM, S. CHIEN and S. N. BHATIA, Nat. Methods 2 (2005) 119

    Article  CAS  Google Scholar 

  4. I. K. KO, K. KATO and H. IWATA, Biomaterials 26 (2005) 4882

    Article  CAS  Google Scholar 

  5. A. REVZIN, P. RAJAGOPALAN, A. W. TILLES, F. BERTHIAUME, M. L. YARMUSH and M. TONER, Langmuir 20 (2004) 2999

    Article  CAS  Google Scholar 

  6. A. KHADEMHOSSEINI, K. Y. SUH, J. M. YANG, G. ENG, J. YEH, S. LEVENBERG and R. LANGER, Biomaterials 25 (2004) 3583

    Article  CAS  Google Scholar 

  7. H. ANDERSSON and A. BERG, Lab Chip 4 (2004) 98

    Article  CAS  Google Scholar 

  8. Y. ITO and M. NOGAWA, Biomaterials 24 (2003) 3021

    Article  CAS  Google Scholar 

  9. J. H. YEON and J. K. PARK, Anal. Biochem. 341 (2005) 308

    Article  CAS  Google Scholar 

  10. J. XU, M. MA and W. M. PURCELL, Toxicol. Appl. Pharmacol. 189 (2003) 100

    Article  CAS  Google Scholar 

  11. B. LAMBERT, L. D. RIDDER, G. SLEGERS, V. GELDER, R. A. DIERCKX and H. THIERENS, Can. J. Physiol. Pharmacol. 82 (2004) 146

    Article  CAS  Google Scholar 

  12. J. M. KELM, N. E. TIMMINS, C. J. BROWN, M. FUSSENEGGER and L. K. NIELSEN, Biotechnol. Bioeng. 83 (2003) 173

    Article  CAS  Google Scholar 

  13. H. OTSUKA, A. HIRANO, Y. NAGASAKI, T. OKANO, Y. HORIIKE and K. KATAOKA, Chembiochem 5 (2004) 850

    Article  CAS  Google Scholar 

  14. M. J. POWERS, D. M. JANIGIAN, K. E. WACK, C. S. BAKER, D. B. STOLZ and L. G. GRIFFITH, Tissue Eng. 8 (2002) 499

    Article  Google Scholar 

  15. Y. TORISAWA, A. TAKAGI, Y. NASHIMOTO, T. YASUKAWA, H. SHIKU and T. MAYSUE, Biomaterials 28 (2007) 559

    Article  CAS  Google Scholar 

  16. J. FUKUDA and K. NAKAZAWA, Tissue Eng. 11 (2005) 1254

    Article  CAS  Google Scholar 

  17. J. FUKUDA, Y. SAKAI and K. NAKAZAWA, Biomaterials 27 (2006) 1061

    Article  CAS  Google Scholar 

  18. K. NAKAZAWA, Y. IZUMI, J. FUKUDA and T. YASUDA, J. Biomater. Sci. Polymer Edn. 17 (2006) 859

    Article  CAS  Google Scholar 

  19. N. KOIDE, K. SAKAGUCHI, Y. KOIDE, K. ASANO, M. KAWAGUCHI, H. MATSUSHITA, T. TAKENAMI, T. SHINJI, M. MORI and T. TSUJI, Exp. Cell Res. 186 (1990) 227

    Article  CAS  Google Scholar 

  20. J. Z. TONG, P. D. LAGAUSIE, V. FURLAN, T. CRESTEIL, O. BERNARD and F. ALVAREZ, Exp. Cell Res. 200 (1992) 326

    Article  CAS  Google Scholar 

  21. H. IJIMA, T. MATSUSHITA, K. NAKAZAWA, Y. FUJII and K. FUNATSU, Tissue Eng. 4 (1998) 213

    Article  CAS  Google Scholar 

  22. S. ZHANG, L. YAN, M. ALTMAN, M. LASSLE, H. NUGENT, F. FRANKEL, D. A. LAUFFENBURGER, G. M. WHITESIDES and A. RICH, Biomaterials 20 (1999) 1213

    Article  CAS  Google Scholar 

  23. R. S. KANE, S. TAKAYAMA, E. OSTUNI, D. E. INGBER and G. M. WHITESIDES, Biomaterials 20 (1999) 2363

    Article  CAS  Google Scholar 

  24. M. KHALIL, A. S. PANAHI, R. TOOTLE, T. RYDER, P. M. CLOSKEY, E. ROBERTS, H. HODGSON and C. SELDEN, J. Hepatol. 34 (2001) 68

    Article  CAS  Google Scholar 

  25. Y. YAMASHITA, M. SHIMADA, E. TSUJITA, S. TANAKA, H. IJIMA, K. NAKAZAWA, R. SAKIYAMA, J. FUKUDA, T. UEDA, K. FUNATSU and K. SUGIMACHI, Cell Transplant. 10 (2001) 717

    CAS  Google Scholar 

  26. J. FUKUDA, K. OKAMURA, K. NAKAZAWA, H. IJIMA, Y. YAMASHITA, M. SHIMADA, K. SHIRABE, E. TSUJITA, K. SUGIMACHI and K. FUNATSU, Cell Transplant. 12 (2003) 51

    CAS  Google Scholar 

Download references

Acknowledgements

This research was supported by funds from the Japanese Ministry of Education, Culture, Sports, Science and Technology (MEXT) via the Kitakyushu innovative cluster project and a Grant-in-Aid for Young Scientists (B) (17760628).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to K. Nakazawa.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Tamura, T., Sakai, Y. & Nakazawa, K. Two-dimensional microarray of HepG2 spheroids using collagen/polyethylene glycol micropatterned chip. J Mater Sci: Mater Med 19, 2071–2077 (2008). https://doi.org/10.1007/s10856-007-3305-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10856-007-3305-1

Keywords

Navigation