Biomedical Microdevices

, Volume 11, Issue 4, pp 795–799

A novel 3-D model for cell culture and tissue engineering

  • Xulang Zhang
  • Yubing Xie
  • Chee Guan Koh
  • L. James Lee


A novel method of making microcapsules in a macrocapsule is demonstrated as a 3-D culture system in this article. Mouse embryonic stem (mES) cells as model cells were used in the 3-D culture space, and the cell viability and histological observation were conducted. Furthermore, Oct4 gene expression was evaluated for the undifferentiated status of mES cells in this 3-D model. The results showed that mES cells can grow in this 3-D model and retain their normal viability and morphology. This 3-D model allows mES cells to stay in the undifferentiated state better than 2-D culture systems. This work demonstrates a new 3-D tissue model which can provide an in vivo like microenvironment for non-differentiated mES cells with good immunoisolation. This approach may bridge the gap between traditional 2-D cell culture and animal models.


Microcapsule Macrocapsule ES cells 3-D cell culture Differentiation 


  1. A. Alavi, D.G. Stupack, Methods Enzymol. 426, 85–101 (2007). doi:10.1016/S0076-6879(07)26005-7 CrossRefGoogle Scholar
  2. T. Ando, H. Yamazoe, K. Moriyasu, Y. Ueda, H. Iwata, Tissue Eng. 13, 2539–2547 (2007). doi:10.1089/ten.2007.0045 CrossRefGoogle Scholar
  3. J. Beck, R. Angus, B. Madsen, D. Britt, B. Vernon, K.T. Nguyen, Tissue Eng 13, 589–599 (2007). doi:10.1089/ten.2006.0183 CrossRefGoogle Scholar
  4. K.A. Beningo, M. Dembo, Y.L. Wang, Proc. Natl. Acad. Sci. USA 101, 18024–18029 (2004). doi:10.1073/pnas.0405747102 CrossRefGoogle Scholar
  5. T.M.S. Chang, Science 146, 524–525 (1964). doi:10.1126/science.146.3643.524 CrossRefGoogle Scholar
  6. T.A. Desai, W.H. Chu, G. Rasi, Biomed. Microdevices 1, 131–138 (1999). doi:10.1023/A:1009948524686 CrossRefGoogle Scholar
  7. T.A. Desai, D.J. Hansford, M. Ferrari, Biomol. Eng. 17, 23–36 (2000). doi:10.1016/S1389-0344(00)00063-0 CrossRefGoogle Scholar
  8. J.P. Frampton, M.R. Hynd, J.C. Williams, M.L. Shuler, W. Shain, J. Neural Eng. 4, 399–409 (2007). doi:10.1088/1741-2560/4/4/006 CrossRefGoogle Scholar
  9. E.P. Herrero, E.M. Del Valle, M.A. Galán, Biotechnol. Prog. 23, 940–945 (2007)Google Scholar
  10. J. Huang, H. Yamaji, H. Fukuda, J. Biosci. Bioeng. 104, 98–103 (2007). doi:10.1263/jbb.104.98 CrossRefGoogle Scholar
  11. D.S. Hwang, S.B. Sim, H.J. Cha, Biomaterials 28, 4039–4046 (2007). doi:10.1016/j.biomaterials.2007.05.028 CrossRefGoogle Scholar
  12. N.S. Hwang, S. Varghese, J. Elisseeff, Adv. Drug Deliv. Rev. 60, 199–214 (2008). doi:10.1016/j.addr.2007.08.036 CrossRefGoogle Scholar
  13. N. Kimura, T. Okegawa, K. Yamazaki, K. Matsuoka, Bioconjug. Chem. 18, 1778–1785 (2007). doi:10.1021/bc070083+ CrossRefGoogle Scholar
  14. Y. Kobayashi, Front. Biosci. 1, 2400–2407 (2008). doi:10.2741/2853 CrossRefGoogle Scholar
  15. C. Kosinski, V.S. Li, A.S. Chan, J. Zhang, C. Ho, W.Y. Tsui, T.L. Chan, R.C. Mifflin, D.W. Powell, S.T. Yuen, S.Y. Leung, X. Chen, Proc. Natl. Acad. Sci. USA 104, 15418–15423 (2007). doi:10.1073/pnas.0707210104 CrossRefGoogle Scholar
  16. J.M. Kuijlen, B.J. de Haan, W. Helfrich, J.F. de Boer, D. Samplonius, J.J. Mooij, P. de Vos, J. Neurooncol. 78, 31–39 (2006)CrossRefGoogle Scholar
  17. X. Ma, I. Vacek, A. Sun, Artif. Cells Blood Substit. Immobil. Biotechnol. 22, 43–69 (1994). doi:10.3109/10731199409117399 CrossRefGoogle Scholar
  18. A.P. McGuigan, D.A. Bruzewicz, A. Glavan, M. Butte, G.M. Whitesides, PLoS ONE. 3, e2258 (2008)CrossRefGoogle Scholar
  19. R. Mueller-Rath, K. Gavénis, S. Gravius, S. Andereya, T. Mumme, U. Schneider, Biomed. Mater. Eng. 17, 357–366 (2007)Google Scholar
  20. L. Nee, N. Tuite, M.P. Ryan, T. McMorrow, Nephron. Exp. Nephrol. 107, e73–86 (2007)CrossRefGoogle Scholar
  21. P.B. Stiegler, V. Stadlbauer, S. Schaffellner, G. Halwachs, C. Lackner, O. Hauser, F. Iberer, K. Tscheliessnigg, Transplant. Proc. 38, 3026–3030 (2006)CrossRefGoogle Scholar
  22. J.A. Thomson, J. Itskovitz-Eldor, S.S. Shapiro, M.A. Waknitz, J.J. Swiergiel, V.S. Marshall, J.M. Jones, Science. 282, 1145–1147 (1998)CrossRefGoogle Scholar
  23. R.J. Walczak, A. Boiarski, T. West, J. Shapiro, S. Sharma, M. Ferrari, Nanobiotech. 1, 35–42 (2005)CrossRefGoogle Scholar
  24. W. Wang, X.D. Liu, Y.B. Xie, H. Zhang, W.T. Yu, Y. Xiong, W.Y. Xie, X.J. Ma, J. Mater. Chem. 16, 3252–3267 (2006)CrossRefGoogle Scholar
  25. X. Zhang, W. Wang, W. Yu, Y. Xie, X. Zhang, Y. Zhang, X. Ma, Biotechnol. Prog. 21, 1289–1296 (2005)CrossRefGoogle Scholar
  26. Y. Zhang, W. Wang, J. Zhou, W. Yu, X. Zhang, X. Guo, X. Ma, Ann. Biomed. Eng. 35, 605–614 (2007)CrossRefGoogle Scholar
  27. X. Zhang; H. He; C. Yen; W. Ho; J. Lee, A biodegradable, immunoprotective, dual nanoporous capsule for cell-based therapies. Biomaterials. 29, 4253–4259 (2008)Google Scholar
  28. H. Zimmermann, S.G. Shirley, U. Zimmermann, Curr. Diab. Rep. 7, 314–320 (2007)CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  • Xulang Zhang
    • 1
  • Yubing Xie
    • 2
  • Chee Guan Koh
    • 3
  • L. James Lee
    • 1
    • 3
  1. 1.Nanoscale Science and Engineering Center for Affordable Nanoengineering of Polymeric Biomedical DevicesThe Ohio State UniversityColumbusUSA
  2. 2.College of Nanoscale Science & EngineeringUniversity at Albany, State University of New YorkAlbanyUSA
  3. 3.Department of Chemical and Bimolecular EngineeringThe Ohio State UniversityColumbusUSA

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