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Hydrogel scaffolds to study cell biology in four dimensions

Published online by Cambridge University Press:  13 March 2013

Katherine J.R. Lewis
Affiliation:
University of Colorado at Boulder; [email protected]
Kristi S. Anseth
Affiliation:
University of Colorado at Boulder; [email protected]
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Abstract

Poly(ethylene glycol) (PEG) hydrogels represent a versatile material scaffold for culturing cells in two or three dimensions with the advantages of limited protein fouling and cytocompatible polymerization to enable cell encapsulation. By using light-based chemistries for gelation and for incorporating biomolecules into the network, dynamic niches can be created that facilitate the study of how cells respond to user-dictated or cell-dictated changes in environmental signals. Specifically, we demonstrate integration of a photo-cleavable molecule into network cross-links and into pendant functional groups to construct gels with biophysical and biochemical properties that are spatiotemporally tunable with light. Complementary to this approach, an enzymatically cleavable peptide sequence can be introduced within hydrogel networks, in this case through photoinitiated addition reactions between thiol-containing biomacromolecules and ene-containing synthetic polymers, to enable cellular remodeling of their surrounding hydrogel microenvironment. With such tunable material platforms, researchers can employ a systematic approach for 3D cell culture experiments, spatially and temporally modulating physical properties (e.g., stiffness) as well as biological signals (e.g., adhesive ligands) to study cell behavior in response to environmental stimuli. Collectively, these material systems suggest routes for new experimentation to study and manipulate cellular functions in four dimensions.

Type
Research Article
Copyright
Copyright © Materials Research Society 2013

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References

1. Reginato, M.J., Mills, K.R., Paulus, J.K., Lynch, D.K., Sgroi, D.C., Debnath, J., Muthuswamy, S.K., Brugge, J.S., Nat. Cell Biol. 5, 733 (2003).Google Scholar
2. Magnusson, M.K., Mosher, D.F., Arterioscler. Thromb. Vasc. Biol. 18, 1363 (1998).Google Scholar
3. Parsons, J.T., Martin, K.H., Slack, J.K., Taylor, J.M., Weed, S.A., Oncogene 19, 5606 (2000).Google Scholar
4. Tibbitt, M.W., Anseth, K.S., Biotechnol. Bioeng. 103, 655 (2009).Google Scholar
5. Taipale, J., Keski-Oja, J., FASEB J. 11, 51 (1997).Google Scholar
6. Kim, S.-H., Turnbull, J., Guimond, S., J. Endocrinol. 209, 139 (2011).Google Scholar
7. Bacac, M., Stamenkovic, I., Annu. Rev. Pathol. 3, 221 (2008).Google Scholar
8. Daley, W.P., Peters, S.B., Larsen, M., J. Cell Sci. 121, 255 (2008).Google Scholar
9. Ingber, D., Annu. Rev. Physiol. 59, 575 (1997).Google Scholar
10. Levental, I., Georges, P.C., Janmey, P.A., Soft Matter 3, 299 (2007).Google Scholar
11. Engler, A.J., Sen, S., Sweeney, H.L., Discher, D.E., Cell 126, 677 (2006).Google Scholar
12. Paszek, M.J., Zahir, N., Johnson, K.R., Lakins, J.N., Rozenberg, G.I., Gefen, A., Reinhart-King, D.A., Margulies, S.S., Dembo, M., Boettiger, D., Hammer, D.A., Weaver, V.M., Cancer Cell 8, 241 (2005).Google Scholar
13. Rosso, F., Marino, G., Giordano, A., Barbarisi, M., Parmeggiani, D., Barbarisi, A., J. Cell. Physiol. 203, 465 (2005).CrossRefGoogle Scholar
14. Lutolf, M.P., Hubbell, J.A., Nat. Biotechnol. 23, 47 (2005).Google Scholar
15. Peppas, N.A., Hilt, J.Z., Khademhosseini, A., Langer, R., Adv. Mater. 18, 1345 (2006).Google Scholar
16. Sawhney, A., Pathak, C., Hubbell, J., Macromolecules 26, 581 (1993).Google Scholar
17. Bryant, S.J., Nuttelman, C.R., Anseth, K.S., J. Biomater. Sci., Polym. Ed. 11, 439 (2000).Google Scholar
18. Bryant, S.J., Anseth, K.S., J. Biomed. Mater. Res. 59, 63 (2002).Google Scholar
19. Cushing, M.C., Anseth, K.S., Science 316, 1133 (2007).Google Scholar
20. Weber, L.M., He, J., Bradley, B., Haskins, K., Anseth, K.S., Acta Biomater. 2, 1 (2006).Google Scholar
21. Cordey, M., Limacher, M., Kobel, S., Taylor, V., Lutolf, M.P., Stem Cells 26, 2586 (2008).Google Scholar
22. Rice, M.A., Anseth, K.S., J. Biomed. Mater. Res. Part A 70, 560 (2004).Google Scholar
23. Nuttelman, C.R., Henry, S.M., Anseth, K.S., Biomaterials 23, 3617 (2002).Google Scholar
24. Bryant, S.J., Anseth, K.S., J. Biomed. Mater. Res. Part A 64, 70 (2003).Google Scholar
25. Lutolf, M.P., Lauer-Fields, J.L., Schmoekel, H.G., Metters, A.T., Weber, F.E., Fields, G.B., Hubbell, J.A., Proc. Natl. Acad. Sci. U.S.A. 100, 5413 (2003).CrossRefGoogle Scholar
26. Salinas, C.N., Anseth, K.S., Biomaterials 29, 2370 (2008).Google Scholar
27. Kloxin, A.M., Kasko, A.M., Salinas, C.N., Anseth, K.S., Science 324, 59 (2009).Google Scholar
28. Bryant, S.J., Anseth, K.S., in Scaffolding in Tissue Engineering, Ma, P.X., Elisseeff, J., Eds. (CRC Press, Boca Raton, FL, 2006), chap. 6, p. 71.Google Scholar
29. Metters, A., Hubbell, J., Biomacromolecules 6, 290 (2005).Google Scholar
30. Kloxin, A.M., Tibbitt, M.W., Kasko, A.M., Fairbairn, J.A., Anseth, K.S., Adv. Mater. 22, 61 (2010).Google Scholar
31. Benton, J.A., Kern, H.B., Anseth, K.S., J. Heart Valve Dis. 17, 689 (2008).Google Scholar
32. Yip, C.Y.Y., Chen, J.-H., Zhao, R., Simmons, C.A., Arterioscler. Thromb. Vasc. Biol. 29, 936 (2009).Google Scholar
33. Kloxin, A.M., Benton, J.A., Anseth, K.S., Biomaterials 31, 1 (2010).Google Scholar
34. Wang, H., Haeger, S.M., Kloxin, A.M., Leinwand, L.A., Anseth, K.S., PloS One 7, e39969 (2012).CrossRefGoogle Scholar
35. Engler, A., Bacakova, L., Newman, C., Hategan, A., Griffin, M., Discher, D., Biophys. J. 86, 617 (2004).Google Scholar
36. Tse, J.R., Engler, A.J., PloS One 6, e15978 (2011).Google Scholar
37. Zaari, N., Rajagopalan, P., Kim, S.K., Engler, A.J., Wong, J.Y., Adv. Mater. 16, 2133 (2004).Google Scholar
38. Ruoslahti, E., Pierschbacher, M.D., Science 238, 491 (1987).Google Scholar
39. Hubbell, J., Nat. Biotechnol. 13, 565 (1995).Google Scholar
40. Burdick, J.A., Anseth, K.S., Biomaterials 23, 4315 (2002).Google Scholar
41. Tavella, S., Bellese, G., Castagnola, P., Martin, I., Piccini, D., Doliana, R., Colombatti, A., Cancedda, R., Tacchetti, C., J. Cell Sci. 110, 2261 (1997).CrossRefGoogle Scholar
42. DeLise, A.M., Fischer, L., Tuan, R.S., Osteoarth. Cartil. 8, 309 (2000).Google Scholar
43. Fairbanks, B.D., Schwartz, M.P., Halevi, A.E., Nuttelman, C.R., Bowman, C.N., Anseth, K.S., Adv. Mater. 21, 5005 (2009).Google Scholar
44. Hoyle, C.E., Bowman, C.N., Angew. Chem. Int. Ed. 49, 1540 (2010).Google Scholar
45. Lutolf, M.P., Tirelli, N., Cerritelli, S., Cavalli, L., Hubbell, J.A., Bioconjugate Chem. 12, 1051 (2001).Google Scholar
46. Elbert, D.L., Hubbell, J.A., Biomacromolecules 2, 430 (2001).Google Scholar
47. Lutolf, M.P., Hubbell, J.A., Biomacromolecules 4, 713 (2003).Google Scholar
48. Lutolf, M.P., Raeber, G.P., Zisch, A.H., Tirelli, N., Hubbell, J.A., Adv. Mater. 15, 888 (2003).Google Scholar
49. Polizzotti, B.D., Fairbanks, B.D., Anseth, K.S., Biomacromolecules 9, 1084 (2008).Google Scholar
50. Anderson, S.B., Lin, C.-C., Kuntzler, D.V., Anseth, K.S., Biomaterials 32, 3564 (2011).Google Scholar
51. Benton, J.A., Fairbanks, B.D., Anseth, K.S., Biomaterials 30, 6593 (2009).Google Scholar
52. Mann, B.K., Gobin, A.S., Tsai, A.T., Schmedlen, R.H., West, J.L., Biomaterials 22, 3045 (2001).Google Scholar
53. Codelli, J.A., Baskin, J.M., Agard, N.J., Bertozzi, C.R., J. Am. Chem. Soc. 130, 11486 (2008).Google Scholar
54. DeForest, C.A., Polizzotti, B.D., Anseth, K.S., Nat. Mater. 8, 659 (2009).Google Scholar
55. DeForest, C.A., Sims, E.A., Anseth, K.S., Chem. Mater. 22, 4783 (2010).Google Scholar
56. DeForest, C.A., Anseth, K.S., Nat. Chem. 3, 925 (2011).Google Scholar