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Structural and molecular micropatterning of dual hydrogel constructs for neural growth models using photochemical strategies

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Abstract

Chemotactic and haptotactic cues guide neurite growth toward appropriate targets by eliciting attractive or repulsive responses from the neurite growth cones. Here we present an integrated system allowing both structural and molecular micropatterning in dual hydrogel 3D tissue culture constructs for directing in vitro neuronal growth via structural, immobilized, and soluble guidance cues. These tissue culture constructs were fabricated into specifiable geometries using UV light reflected from a digital micromirror device acting as a dynamic photomask, resulting in dual hydrogel constructs consisting of a cell growth-restrictive polyethylene glycol (PEG) boundary with a cell growth-permissive interior of photolabile α-carboxy-2-nitrobenzyl cysteine agarose (CNBC-A). This CNBC-A was irradiated in discrete areas and subsequently tagged with maleimide-conjugated biomolecules. Fluorescent microscopy showed biomolecule binding only at the sites of irradiation in CNBC-A, and confocal microscopy confirmed 3D binding through the depth of the construct. Neurite outgrowth studies showed contained growth throughout CNBC-A. The diffusion rate of soluble fluorescein-bovine serum albumin through the dual hydrogel construct was controlled by PEG concentration and the distance between the protein source and the agarose interior; the timescale for a transient protein gradient changed with these parameters. These findings suggest the dual hydrogel system is a useful platform for manipulating a 3D in vitro microenvironment with patterned structural and molecular guidance cues for modeling neural growth and guidance.

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References

  • A. Abbott, Nature 424, 870–872 (2003)

    Article  Google Scholar 

  • L. Almany, D. Seliktar, Biomaterials 26, 2467–2477 (2005)

    Article  Google Scholar 

  • A.P. Balgude, X. Yu, A. Szymanski, R.V. Bellamkonda, Biomaterials 22, 1077–1084 (2001)

    Article  Google Scholar 

  • R.V. Bellamkonda, J.P. Ranieri, P. Aebischer, J. Neurosci. Res. 41, 501–509 (1995)

    Article  Google Scholar 

  • A. Bernard, J.P. Renault, B. Michel, H.R. Bosshard, E. Delamarche, Adv. Mater. 12, 1067–1070 (2000)

    Article  Google Scholar 

  • N. Bhattacharjee, N.Z. Li, T.M. Keenan, A. Folch, Integr. Biol. 2, 669–679 (2010)

    Article  Google Scholar 

  • M.J. Bissell, D. Radisky, Nat. Rev. Cancer 1, 46–54 (2001)

    Article  Google Scholar 

  • S.J. Bryant, K.S. Anseth, J. Biomed. Mater. Res. 59, 63–72 (2002)

    Article  Google Scholar 

  • S.J. Bryant, K.S. Anseth, J. Biomed. Mater. Res. A 64A, 70–79 (2003)

    Article  Google Scholar 

  • E. Cukierman, R. Pankov, D.R. Stevens, K.M. Yamada, Science 294, 1708–1712 (2001)

    Article  Google Scholar 

  • J.L. Curley, M.J. Moore, J. Biomed. Mater. Res. A 99A, 532–543 (2011)

    Article  Google Scholar 

  • J.L. Curley, S.R. Jennings, M.J. Moore, J. Vis. Exp. 48, e2636 (2011)

    Google Scholar 

  • A. Desai, W.S. Kisaalita, C. Keith, Z.Z. Wu, Biosens. Bioelectron. 21, 1483–1492 (2006)

    Article  Google Scholar 

  • B. Dhariwala, E. Hunt, T. Boland, Tissue Eng. 10, 1316–1322 (2004)

    Google Scholar 

  • M.S. Hahn, L.J. Taite, J.J. Moon, M.C. Rowland, K.A. Ruffino, J.L. West, Biomaterials 27, 2519–2524 (2006)

    Article  Google Scholar 

  • M.J. Hansen, G.E. Dallal, J.G. Flanagan, Neuron 42, 717–730 (2004)

    Article  Google Scholar 

  • H.R. Irons, D.K. Cullen, N.P. Shapiro, N.A. Lambert, R.H. Lee, M.C. Laplaca, J. Neural Eng. 5, 333–341 (2008)

    Article  Google Scholar 

  • K. Kim, A. Yeatts, D. Dean, J.P. Fisher, Tissue Eng. Part B Rev. 16, 523–539 (2010)

    Article  Google Scholar 

  • A.M. Kloxin, A.M. Kasko, C.N. Salinas, K.S. Anseth, Science 324, 59–63 (2009)

    Article  Google Scholar 

  • C.R. Kothapalli, E. van Veen, S. de Valence, S. Chung, I.K. Zervantonakis, F.B. Gertler, R.D. Kamm, Lab Chip 11, 497–507 (2011)

    Article  Google Scholar 

  • N. Kotzur, B. Briand, M. Beyerman, V. Hagan, Chem. Comm, 3255–3257 (2009)

  • C.Y. Chang, B. Niblack, B. Walker, H. Bayley, Chem Biol 2, 391–400 (1995)

    Article  Google Scholar 

  • K.Y. Lee, D.J. Mooney, Chem. Rev. 101, 1869–1879 (2001)

    Article  Google Scholar 

  • K.N. Lee, D.S. Shin, Y.S. Lee, Y.K. Kim, J. Micromech. Microeng. 13, 18–25 (2003)

    Article  Google Scholar 

  • J. Lee, M.J. Cuddihy, N.A. Kotov, Tissue Eng. Part B Rev. 14, 61–86 (2008a)

    Article  Google Scholar 

  • S.H. Lee, J.J. Moon, J.L. West, Biomaterials 29, 2962–2968 (2008b)

    Article  Google Scholar 

  • K. Lehmann, M. Herklotz, M. Espig, T. Paumer, M. Nitschke, C. Werner, T. Pompe, Biomaterials 31, 8802–8809 (2010)

    Article  Google Scholar 

  • Y. Lu, G. Mapili, G. Suhali, S.C. Chen, K. Roy, J. Biomed. Mater. Res. A 77A, 396–405 (2006)

    Article  Google Scholar 

  • Y. Luo, M.S. Shoichet, Biomacromolecules 5, 2315–2323 (2004a)

    Article  Google Scholar 

  • Y. Luo, M.S. Shoichet, Nat. Mater. 3, 249–253 (2004b)

    Article  Google Scholar 

  • M.P. Lutolf, J.A. Hubbell, Nat. Biotechnol. 23, 47–55 (2005)

    Article  Google Scholar 

  • F.P.W. Melchels, K. Bertoldi, R. Gabbrielli, A.H. Velders, J. Feijen, D.W. Grijpma, Biomaterials 31, 6909–6916 (2010)

    Article  Google Scholar 

  • J.J. Moon, S.H. Lee, J.L. West, Biomacromolecules 8, 42–49 (2007)

    Article  Google Scholar 

  • S. Nemir, H.N. Hayenga, J.L. West, Biotechnol. Bioeng. 105, 636–644 (2010)

    Article  Google Scholar 

  • K.T. Nguyen, J.L. West, Biomaterials 23, 4307–4314 (2002)

    Article  Google Scholar 

  • P. Pan, H. Bayley, FEBS Lett. 405, 81–85 (1997)

    Article  Google Scholar 

  • N.A. Peppas, Y. Huang, M. Torres-Lugo, J.H. Ward, J. Zhang, Annu. Rev. Biomed. Eng. 2, 9–29 (2000)

    Article  Google Scholar 

  • A. Ribeiro, S. Vargo, E.M. Powell, J.B. Leach, Tissue Eng. Part A 18, 93–102 (2012)

    Article  Google Scholar 

  • W.J. Rosoff, J.S. Urbach, R.G. McAllister, L.J. Richards, G.J. Goodhill, Nat. Neurosci. 7, 678–682 (2004)

    Article  Google Scholar 

  • A.C. Von Philipsborn, S. Lang, A. Bernard, J. Loeschinger, C. David, D. Lehnert, M. Bastmeyer, F. Bonhoeffer, Nat. Protoc. 1, 1322–1328 (2006)

    Article  Google Scholar 

  • J.W. Walker, S.H. Gilbert, R.M. Drummond, M. Yamada, R. Sreekumar, R.E. Carraway, M. Ikebe, F.S. Fay, Proc Nat Acad Sci USA 95, 1568–1573 (1998)

    Article  Google Scholar 

  • S. Wang, C.W.P. Foo, A. Warrier, M.M. Poo, S.C. Heilshorn, X. Zhang, Biomed Microdev 11, 1127–1134 (2009)

    Article  Google Scholar 

  • V.M. Weaver, O.W. Petersen, F. Wang, C.A. Larabell, P. Briand, C. Damsky, M.J. Bissell, J. Cell Biol. 137, 231–245 (1997)

    Article  Google Scholar 

  • D.G. Wilkinson, Nat. Rev. Neurosci. 2, 155–164 (2001)

    Article  Google Scholar 

  • S.E. Williams, C.A. Mason, E. Herrera, Curr. Opin. Neurobiol. 14, 51–60 (2004)

    Article  Google Scholar 

  • T.W. Yu, C.I. Bargmann, Nat. Neurosci. 4, 1169–1176 (2001)

    Article  Google Scholar 

  • S. Zalipsky, J. M. Harris, in Poly(Ethylene Glycol), ed. by J. M. Harris, S. Zalipsky (American Chemical Society, Washington, DC, 1997), pp. 1–13

  • J.M. Zhu, Biomaterials 31, 4639–4656 (2010)

    Article  Google Scholar 

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Acknowledgments

This research was funded in part by grants from the Louisiana Board of Regents (LEQSF[2009-10]-RD-A-18), the NIH (NS065374), and an NSF CAREER award to MJM (CBET-1055990). We also thank Chris Rodell for assistance with tBu-BNPA synthesis.

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Authors and Affiliations

  1. Department of Biomedical Engineering, Tulane University, New Orleans, LA, 70118, USA

    Elaine L. Horn-Ranney, J. Lowry Curley, Gary C. Catig, Renee M. Huval & Michael J. Moore

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  1. Elaine L. Horn-Ranney
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  2. J. Lowry Curley
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  3. Gary C. Catig
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  4. Renee M. Huval
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  5. Michael J. Moore
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Correspondence to Michael J. Moore.

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Horn-Ranney, E.L., Curley, J.L., Catig, G.C. et al. Structural and molecular micropatterning of dual hydrogel constructs for neural growth models using photochemical strategies. Biomed Microdevices 15, 49–61 (2013). https://doi.org/10.1007/s10544-012-9687-y

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