Abstract
This paper describes a simple reversible hydrogel patterning method for 3D cell culture. Alginate gel is formed in select regions of a microfluidic device through light-triggered release of caged calcium. In the pre-gelled alginate solution, calcium is chelated by DM-nitrophen (DM-n) to prevent cross-linking of alginate. After sufficient UV exposure the caged calcium is released from DM-n causing alginate to cross-link. The effect of using different concentrations of calcium and chelating agents as well as the duration of UV exposure is described. Since the cross-linking is based on calcium concentration, the cross-linked alginate can easily be dissolved by EDTA. We also demonstrate application of this capability to patterned microscale 3D co-culture using endothelial cells and osteoblastic cells in a microchannel.
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E. Alsberg, K.W. Anderson, R.T. Franceschi, D.J. Mooney, J. Dent. Res. 80, 2025–2029 (2001)
K. Arcaute, B.K. Mann, R.B. Wicker, Ann. Biomed. Eng. 34, 1429–1441 (2006)
T. Braschler, R. Johann, M. Heule, L. Metref, P. Rnaud, Lab Chip 5, 553–559 (2005)
M. Cabodi, N.W. Choi, J.P. Gleghorn, C.S.D. Lee, L.J. Bonassar, A.D.J. Stroock, J. Am. Chem. Soc. 127, 13788–13789 (2005)
J.-P. Chen, T.-H. Cheng, Polymer 50, 107–116 (2009)
D. Dendukuri, S.S. Gu, D.C. Pregibon, T.A. Hatton, P.S. Doyle, Lab Chip 7, 818–828 (2007)
D.C. Duffy, J.C. McDonald, O.J.A. Schueller, G.M. Whitesides, Anal. Chem. 70, 4974–4984 (1998)
G.C.R. Ellis-Davis, Nat. Methods. 4, 619–628 (2007)
G.C.R. Ellis-Davis, Meth Enzymol. 360A, 226–238 (2003)
N.W. Choi, M. Cabodi, B. Held, J.P. Gleghorn, L.J. Bonassar, A.D. Stroock, Nat. Mater. 7, 908–915 (2007)
E. Cukierman, R. Pankov, D.R. Stevens, K.M. Yamada, Science 294, 1708–1712 (2001)
C. Fishbach, H.J. Kong, S.X. Hsiong, M.B. Evangelista, W. Yuen, D.J. Mooney, Proc. Natl. Acad. Sci. U.S.A. 106, 399–404 (2009)
G.T. Franzesi, B. Ni, Y. Ling, A.J. Khademhosseini, J. Am, Chem. Soc. 128, 15064–15065 (2006)
B.M. Gillette, J.A. Jensen, B. Tang, G.J. Yang, A. Bazargan-Lari, M. Zhong, S.K. Sia, Nat. Mater. 7, 636–640 (2008)
L.G. Griffith, M.A. Swartz, Nat. Rev. Mol. Cell Biol. 7, 211–224 (2007)
A.P. Golden, J. Tien, Lab Chip 7, 720–725 (2007)
M.S. Hahn, J.S. Miller, J.L. West, Adv. Mater. 18, 2679–2684 (2006)
X. Hao, E.A. Silva, A. Mansson-Broberg, K. Grinnemo, A.J. Siddiqui, G. Dellgren, E. Wardell, L.A. Brodin, D.J. Mooney, C. Sylven, Cardiovasc. Res. 75, 178–185 (2007)
L. Hughes, D.A. Ledward, J.R. Mitchell, C.J. Summerlin, Texture Studies 11, 247–256 (1980)
A.M. Kloxin, A.M. Kasko, C.N. Salinas, K.S. Anseth, Science 324, 59–63 (2009)
W.G. Koh, A. Revzin, M.V. Pishko, Langmuir 18, 2459–2462 (2002)
H.J. Kong, E. Wong, D.J. Mooney, Macromolecules 36, 4582–4588 (2003)
H.J. Kong, K.Y. Lee, D.J. Mooney, Polymer 43, 6239–6246 (2002)
K. Liu, H. Ding, J. Liu, Y. Chen, X. Zhao, Langmuir 22, 9453–9457 (2006)
C.M. Nelson, M.M. VanDuijn, J.L. Inman, D.A. Fletcher, M.J. Bissell, Science 314, 298–300 (2006)
C.M. Nelson, J. Tien, Curr. Opin. Biotechnol. 17, 518–523 (2006)
J.W. Nichol, A. Khademhosseini, Soft Matter 5, 1312–1319 (2009)
P. Panda, S. Ali, E. Lo, B.G. Chung, T.A. Hatton, A. Khademhosseini, P.S. Doyle, Lab Chip 8, 1056–1061 (2008)
N.S. Peppas, J.Z. Hily, A. Khademhosseini, R. Langer, Adv. Mater. 18, 1345–1360 (2006)
B.D. Plouffe, M.A. Brown, R.K. Iyer, M. Radisic, S.K. Murthy, Lab Chip 9, 1507–1510 (2009)
J. Rettig, E. Neher, Science 298, 781–785 (2002)
J.A. Rowley, G. Madlambayan, D.J. Mooney, Biomaterials 20, 45–53 (1999)
R.W. Sands, D.J. Mooney, Curr. Opin. Biotechnol. 18, 448–453 (2007)
S.R. Sershen, G.A. Mensing, M. Ng, N.J. Halas, D.J. Beebe, J.L. West, Adv. Mat. 17, 1366–1368 (2005)
J.H. Sung, M.L. Shuler, Lab Chip 9, 1385–1394 (2009)
W. Tan, T.A. Deasi, Biomaterials 25, 1355–1364 (2004)
M.D. Tang, A.P. Golden, J. Tien, J. Am. Chem. Soc. 125, 12988–12989 (2003)
V.L. Tsang, A.A. Chen, L.M. Cho, K.D. Jadin, R.L. Sah, S. DeLong, J.L. West, S.N. Bhatia, FASEB J. 21, 790–801 (2007)
A.P. Wong, R. Perez-Castillejos, J.C. Love, G.M. Whitesides, Biomaterials 29, 1853–1861 (2008)
G. Xiao, Y. Cui, P. Ducy, G. Karsenty, R.T. Franceschi, Mol. Endo. 11, 1103–1113 (1997)
K.Y. Yamada, E. Cukierman, Cell 130, 601–610 (2007)
H. Yan, A. Nyjnen, J. Ruokolainen, D. Farrar, J.E. Gough, A. Saiani, A.F. Millar, Faraday Discuss 139, 71–84 (2008a)
H. Yan, Y. Zhao, C. Qiu, H. Wu, Sens. Actuators, B 132, 20–25 (2008b)
Acknowledgement
This material is based on work supported by the U.S. Army Research Laboratory and the U.S. Army Research Office under Contract Grant DAAD19-03-1-0168 and the NIH (HG004653).
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Chueh, Bh., Zheng, Y., Torisawa, Ys. et al. Patterning alginate hydrogels using light-directed release of caged calcium in a microfluidic device. Biomed Microdevices 12, 145–151 (2010). https://doi.org/10.1007/s10544-009-9369-6
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DOI: https://doi.org/10.1007/s10544-009-9369-6