Biomedical Microdevices

, Volume 4, Issue 4, pp 257–266 | Cite as

Three-Dimensional Photopatterning of Hydrogels Containing Living Cells

Article

Abstract

Recent advances in tissue engineering have leveraged progress in both polymer chemistry and cell biology. For example, photopolymerizable biomaterials have been developed that can be used to photoencapsulate cells in peptide-derivatized hydrogel networks. While these materials have been useful in bone, cartilage and vascular tissue engineering, they have limited applicability to more complex tissues that are characterized by precise cell and tissue organization (e.g., liver, kidney). Typically, the tissue shape has been defined solely by the container used for photopolymerization. In this paper, we describe the use of photolithographic techniques to broaden the capability of photopolymerizable PEG-based biomaterials by inclusion of structural features within the cell/hydrogel network. Specifically, we describe the development of a photopatterning technique that allows localized photoencapsulation of live mammalian cells to control the tissue architecture. In this study, we optimized the effect of ultraviolet (UV) exposure and photoinitiator concentration on both photopatterning resolution and cell viability. With regard to photopatterning resolution, we found that increased UV exposure broadens feature size, while photoinitiator concentration had no significant effect on patterning resolution. Cell viability was characterized using HepG2 cells, a human hepatoma cell line. We observed that UV exposure itself did not cause cell death over the doses and time scale studied, while the photoinitiator 2,2-dimethoxy-2-phenyl-acetophenone was itself cytotoxic in a dose-dependent manner. Furthermore, the combination of UV and photoinitiator was the least biocompatible condition presumably due to formation of toxic free radicals. The utility of this method was demonstrated by photopatterning hydrogels containing live cells in various single layer structures, patterns of multiple cellular domains in a single “hybrid” hydrogel layer, and patterns of multiple cell types in multiple layers simulating use in a tissue engineering application. The combination of microfabrication approaches with photopolymerizable biomaterials will have implications in tissue engineering, elucidating fundamental structure–function relationships of tissues, and formation of immobilized cell arrays for biotechnological applications.

photopolymerization hydrogels patterning poly (ethylene glycol) 

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References

  1. S.F. Badylak, K. Park, N. Peppas, G. McCabe, and M. Yoder, Exp. Hematol. 29(11), 1310-1318 (2001).Google Scholar
  2. D.J. Beebe, J.S. Moore, J.M. Bauer, Y. Qing, R.H. Liu, C. Devadoss, and J. Byung-Ho, Nature 404(6778), 588-590 (2000).Google Scholar
  3. S.N. Bhatia, U.J. Balis, M.L. Yarmush, and M. Toner, Faseb Journal 13(14), 1883-1900 (1999).Google Scholar
  4. S.N. Bhatia and C.S. Chen, Biomedical Microdevices 2(2), 131-144 (1999).Google Scholar
  5. S.J. Bryant and K.S. Anseth, J. Biomed. Mater. Res. 59(1), 63-72 (2002).Google Scholar
  6. S.J. Bryant, C.R. Nuttelman, and K.S. Anseth, J. Biomater. Sci. Polym. Ed. 11(5), 439-457 (2000).Google Scholar
  7. G. Chen, Y. Imanishi, and Y. Ito, Langmuir 14, 6610-6612 (1998).Google Scholar
  8. G.M. Cruise, O.D. Hegre, D.S. Scharp, and J.A. Hubbell, Biotechnology and Bioengineering 57(6), 655-656 (1998).Google Scholar
  9. G.M. Cruise, D.S. Scharp, and J.A. Hubbell, Biomaterials 19(14), 1287-1294 (1998).Google Scholar
  10. J. Elisseeff, W. McIntosh, K. Anseth, S. Riley, P. Ragan, and R. Langer, Journal of Biomedical Materials Research 51(2), 164-171 (2000).Google Scholar
  11. A.S. Gobin and J.L. West, Faseb J. 16(7), 751-753 (2002).Google Scholar
  12. L.G. Griffith, B. Wu, M.J. Cima, M.J. Powers, B. Chaignaud, and J.P. Vacanti, Ann. N.Y. Acad. Sci. 831, 382-397 (1997).Google Scholar
  13. D.L. Hern and J.A. Hubbell, Journal of Biomedical Materials Research 39(2), 266-276 (1998).Google Scholar
  14. R. Langer and J.P. Vacanti, Science 260(5110), 920-926 (1993).Google Scholar
  15. K.Y. Lee, M.C. Peters, K.W. Anderson, and D.J. Mooney, Nature 408(6815), 998-1000 (2000).Google Scholar
  16. P.X. Ma and R. Zhang, J. Biomed. Mater. Res. 56(4), 469-477 (2001).Google Scholar
  17. M. Madou, Fundamentals of Microfabrication (CRC Press, New York, 1997).Google Scholar
  18. B.K. Mann, A.S. Gobin, A.T. Tsai, R.H. Schmedlen, and J.L. West, Biomaterials 22(22), 3045-3051 (2001).Google Scholar
  19. B.K. Mann, R.H. Schmedlen, and J.L. West, Biomaterials 22(5), 439-444 (2001).Google Scholar
  20. M.B. Mellott, K. Searcy, and M.V. Pishko, Biomaterials 22(9), 929-941 (2001).Google Scholar
  21. N.A. Peppas, P. Bures, W. Leobandung, and H. Ichikawa, Eur. J. Pharm. Biopharm. 50(1), 27-46 (2000).Google Scholar
  22. J.H. Ward, R. Bashir, and N.A. Peppas, J. Biomed. Mater. Res. 56(3), 351-360 (2001).Google Scholar
  23. T.H. Yang, H. Miyoshi, and N. Ohshima, J. Biomed. Mater. Res. 55(3), 379-386 (2001).Google Scholar
  24. T. Yu, F. Chiellini, D. Schmaljohann, R. Solaro, and C.K. Ober, Polymer Preprints 41(2), 1699-1700 (2000).Google Scholar

Copyright information

© Kluwer Academic Publishers 2002

Authors and Affiliations

  1. 1.Departments of Bioengineering and MedicineUniversity of CaliforniaSan Diego, La Jolla

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