Hostname: page-component-77c89778f8-rkxrd Total loading time: 0 Render date: 2024-07-20T16:28:59.308Z Has data issue: false hasContentIssue false

Functional Tissue Engineering Through Biofunctional Macromolecules and Surface Design

Published online by Cambridge University Press:  31 January 2011

Lorenzo Moroni
Institute for Biomedical Technology and Technical Medicine, University of Twente, The Netherlands; e-mail
Pamela Habibovic
Institute for Biomedical Technology and Technical Medicine, University of Twente, The Netherlands; e-mail
David J. Mooney
School of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138, USA; e-mail mooneyd@deas.harvard. edu.
Clemens A. van Blitterswijk
Institute for Biomedical Technology and Technical Medicine, University of Twente, The Netherlands; e-mail
Get access


Tissue engineering is a rapidly developing discipline that has already entered the clinics and will tremendously change patient management in the near future. The aim of classical tissue engineering is to heal damaged or diseased tissues and organs through the combination of cells, biological factors, and porous biomaterials. The resulting, engineered tissue must possess appropriate functional properties to replace or supplement the targeted tissue. This is still a challenge to overcome before tissue-engineered products can be considered a complete success. Classical tissue engineering approaches rely on the use of mature cells expanded in vitro and transplanted alone or seeded in passive 3D scaffolds, which can lead to the loss of cellular phenotype and production of nonfunctional extracellular matrix. An emerging strategy involves the design of bioactive 3D scaffolds with instructive properties able to recruit cells in situ and direct tissue formation. Here, we present and discuss recent efforts to achieve smart scaffolds encompassing macromolecular biofunctionalization and surface design.

Research Article
Copyright © Materials Research Society 2010

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)


1.Behrens, P., Bitter, T., Kurz, B., Russlies, M., Th Knee 13, 194 (2006).CrossRefGoogle Scholar
2.Pavesio, A.Abatangelo, G., Borrione, A., Brocchetta, D., Hollander, A.P., Kon, E., Torasso, F., Zanasi, S., Marcacci, M., Novartis Foundation Symp 249, 203 (2003).CrossRefGoogle Scholar
3.Sadick, N., Sorhaindo, L., Expert Rev. Med Devices 4, 559 (2007).CrossRefGoogle Scholar
4.Arnesen, H., Lunde, K., Aakhus, S., Forfang, K., Lancet 369, 2142 (2007).Google Scholar
5.Takahashi, J., Expert Rev. Neurother. 7, 667 (2007).Google Scholar
6.Brittberg, M., Peterson, L., Sjogren-Jansson, E.Tallheden, T., Lindahl, A., J. Bone Joint Surg. Am 85-A (Suppl. 3), 109 (2003).Google Scholar
7.Varghese, S., Hwang, N.S., Canver, A.C., Theprungsirikul, P., Lin, D.W., Elisseeff, J., Matrix Biol. 27, 12 (2007).CrossRefGoogle Scholar
8.Elisseeff, J., Puleo, C., Yang, F., Sharma, B., Orthod. Craniofac. Res. 8, 150 (2005).CrossRefGoogle Scholar
9.Hollister, S.J., Nat. Mater. 4, 518 (2005).CrossRefGoogle Scholar
10.Hutmacher, D.W., J. Biomater. Sci. Polym. Ed 12, 107 (2001).CrossRefGoogle Scholar
11.Moroni, L., Elisseeff, J.H., Materials Today 11 44 (2008).CrossRefGoogle Scholar
12.Sohier, J., Vlugt, T.J., Cabrol, N., Van Blitterswijk, C., de Groot, K., Bezemer, J.M., J Control Release 111, 95 (2006).CrossRefGoogle Scholar
13.Wang, Y., Bansal, V., Zelikin, A.N., Caruso, F.Nano Lett. 8, 1741 (2008).CrossRefGoogle Scholar
14.Kong, H.J., Mooney, D.J., Nat. Rev. Drug Discov. 6, 455 (2007).CrossRefGoogle Scholar
15.Lutolf, M.P., Hubbell, J.A., Nat. Biotechnol. 23, 47 (2005).CrossRefGoogle Scholar
16.Dalby, M.J., Gadegaard, N., Tare, R., Andar, A., Riehle, M.O., Herzyk, P., Wilkinson, C.D., Oreffo, R.O., Nat. Mater. 6, 997 (2007).Google Scholar
17.Ruiz, S.A., Chen, C.S., Stem Cells 26, 2921 (2008).Google Scholar
18.Alsberg, E., von Recum, H.A., Mahoney, M.J., Expert Opin. Biol. Ther. 6, 847 (2006).CrossRefGoogle Scholar
19.Mrksich, M., Dike, L.E., Tien, J., Ingber, D.E., Whitesides, G.M., Exp. Cell Res. 235, 305 (1997).CrossRefGoogle Scholar
20.Engler, A.J., Sen, S., Sweeney, H.L., Discher, D.E., Cell 126, 677 (2006).Google Scholar
21.Evans, N.D., Minelli, C., Gentleman, E., LaPointe, V., Patankar, S.N., Kallivretaki, M., Chen, X., Roberts, C.J., Stevens, M.M., Eur. Cell. Mater. 18, 1 (2009).Google Scholar
22.Fischbach, C., Mooney, D.J., Biomaterials 28, 2069 (2007).CrossRefGoogle Scholar
23.Chen, R.R., Silva, E.A., Yuen, W.W., Brock, A.A., Fischbach, C., Lin, A.S., Guldberg, R.E., Mooney, D.J., FASEB J. 21, 3896 (2007).Google Scholar
24.Park, J.Y., Kim, S.K., Woo, D.H., Lee, E.J., Kim, J.H., Lee, S.H., Stem Cells 27, 2646 (2009).Google Scholar
25.Shamloo, A., Ma, N., Poo, M.M., Sohn, L.L., Heilshorn, S.C., Lab Chip 8, 1292 (2008).CrossRefGoogle Scholar
26.Silva, E.A., Mooney, D.J., Biomaterials 31, 1235 (2010).Google Scholar
27.Langer, R., Nature 392, 5 (1998).Google Scholar
28.Kang, C.E., Poon, P.C., Tator, C.H., Shoichet, M.S., Tissue Eng. Part A 15, 595 (2009).Google Scholar
29.Sawyer, A.A., Song, S.J., Susanto, E., Chuan, P., Lam, C.X., Woodruff, M.A., Hutmacher, D.W., Cool, S.M., Biomaterials 30, 2479 (2009).Google Scholar
30.Sakiyama-Elbert, S.E., Panitch, A., Hubbell, J.A., FASEB J. 15, 1300 (2001).CrossRefGoogle Scholar
31.Ehrbar, M., Djonov, V.G., Schnell, C., Tschanz, S.A., Martiny-Baron, G., Schenk, U., Wood, J., Burri, P.H., Hubbell, J.A., Zisch, A.H., Circ. Res. 94, 1124 (2004).Google Scholar
32.Lutolf, M.P., Weber, F.E., Schmoekel, H.G., Schense, J.C., Kohler, T., Muller, R., Hubbell, J.A., Nat. Biotechnol. 21, 513 (2003).CrossRefGoogle Scholar
33.Jay, S.M., Shepherd, B.R., Andrejecsk, J.W., Kyriakides, T.R., Pober, J.S., Saltzman, W.M., Biomaterials 31, 3054 (2010).CrossRefGoogle Scholar
34.Hsieh, P.C.H., Davis, M.E., Gannon, J., MacGillivray, C., Lee, R.T., J. Clin. Invest. 116, 237 (2006).Google Scholar
35.Borselli, C., Storrie, H., Benesch-Lee, F., Shvartsman, D., Cezar, C., Lichtman, J.W., Vandenburgh, H.H., Mooney, D.J., Proc. Natl. Acad. Sci. U.S.A. 107, 3287 (2010).Google Scholar
36.Young, S., Patel, Z.S., Kretlow, J.D., Murphy, M.B., Mountziaris, P.M., Baggett, L.S., Ueda, H., Tabata, Y., Jansen, J.A., Wong, M., Mikos, A.G., Tissue Eng. Part A 15, 2347 (2009).Google Scholar
37.Sun, Q., Silva, E.A., Wang, A., Fritton, J.C., Mooney, D.J., Schaffler, M.B., Grossman, P.M., Rajagopalan, S., Pharm. Res. 27, 264 (2010).CrossRefGoogle Scholar
38.Yilgor, P., Tuzlakoglu, K., Reis, R.L., Hasirci, N., Hasirci, V., Biomaterials 30, 3551 (2009).CrossRefGoogle Scholar
39.Curran, J.M., Chen, R., Hunt, J.A., Biomaterials 27, 4783 (2006).Google Scholar
40.Curran, J.M., Chen, R., Hunt, J.A., Biomaterials 31, 1463 (2010).Google Scholar
41.DeForest, C.A., Polizzotti, B.D., Anseth, K.S., Nat. Mater. 8, 659 (2009).Google Scholar
42.Kloxin, A.M., Kasko, A.M., Salinas, C.N., Anseth, K.S., Science 324, 59 (2009).Google Scholar
43.Kim, J., Yoon, J., Hayward, R.C., Nat. Mater. 9, 159 (2010).Google Scholar
44.Saha, K., Pollock, J.F., Schaffer, D.V., Healy, K.E., Curr. Opin. Chem. Biol. 11, 381 (2007).Google Scholar
45.Zhang, K.C., Sugawara, A., Tirrell, D.A., Chembiochem 10, 2617 (2009).Google Scholar
46.Comisar, W.A., Hsiong, S.X., Kong, H.J., Mooney, D.J., Linderman, J.J., Biomaterials 27, 2322 (2006).Google Scholar
47.Patel, S., Tsang, J., Harbers, G.M., Healy, K.E., Li, S., J. Biomed. Mater. Res. A 83, 423 (2007).CrossRefGoogle Scholar
48.Hsiong, S.X., Huebsch, N., Fischbach, C., Kong, H.J., Mooney, D.J., Biomacromol. 9, 1843 (2008).CrossRefGoogle Scholar
49.Cushing, M.C., Liao, J.T., Jaeggli, M.P., Anseth, K.S., Biomater. 28, 3378 (2007).Google Scholar
50.Weber, L.M., Hayda, K.N., Haskins, K., Anseth, K.S., Biomater. 28, 3004 (2007).Google Scholar
51.Gunn, J.W., Turner, S.D., Mann, B.K., J. Biomed. Mater. Res. A 72, 91 (2005).CrossRefGoogle Scholar
52.Hwang, N.S., Varghese, S., Lee, H.J., Theprungsirikul, P., Canver, A., Sharma, B., Elisseeff, J., FEBS Lett. 581, 4172 (2007).Google Scholar
53.Raeber, G.P., Lutolf, M.P., Hubbell, J.A., Biophys. J. 89, 1374 (2005).Google Scholar
54.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
55.Gelain, F., Horii, A., Zhang, S., Macromol. Biosci. 7, 544 (2007).Google Scholar
56.Hartgerink, J.D., Beniash, E., Stupp, S.I., Science 294, 1684 (2001).Google Scholar
57.Mata, A., Hsu, L., Capito, R., Aparicio, C., Henrikson, K., Stupp, S.I., Soft Mat. 5, 1228 (2009).Google Scholar
58.Capito, R.M., Azevedo, H.S., Velichko, Y.S., Mata, A., Stupp, S.I., Science 319, 1812 (2008).CrossRefGoogle Scholar
59.Cui, H., Muraoka, T., Cheetham, A.G., Stupp, S.I., Nano Lett. 9, 945 (2009).Google Scholar
60.Mei, Y., Cannizzaro, C., Park, H., Xu, Q., Bogatyrev, S.R., Yi, K., Goldman, N., Langer, R., Anderson, D.G., Small 4, 1600 (2008).Google Scholar
61.Curran, J.M., Chen, R., Stokes, R., Irvine, E., Graham, D., Gubbins, E., Delaney, D., Amro, N., Sanedrin, R., Jamil, H., Hunt, J.A., J. Mater. Sci. Mater. Med. 21, 1021 (2009).Google Scholar
62.Thapa, A., Webster, T.J., Haberstroh, K.M., J. Biomed. Mater. Res. A 67, 1374 (2003).Google Scholar
63.Thapa, A., Miller, D.C., Webster, T.J., Haberstroh, K.M., Biomater. 24, 2915 (2003).Google Scholar
64.Claase, M.B., Olde Riekerink, M.B., de Bruijn, J.D., Grijpma, D.W., Engbers, G.H., Feijen, J., Biomacromol. 4, 57 (2003).Google Scholar
65.Chim, H., Ong, J.L., Schantz, J.T., Hutmacher, D.W., Agrawal, C.M., J. Biomed. Mater. Res. A 65, 327 (2003).Google Scholar
66.Nelea, V., Luo, L., Demers, C.N., Antoniou, J., Petit, A., Lerouge, S., Wertheimer, R., Mwale, F., J. Biomed. Mater. Res. A 75, 216 (2005).Google Scholar
67.Lipski, A.M., Jaquiery, C., Choi, H., Eberli, D., Stevens, M., Martin, I., Chen, I.W., Shastri, V.P., Adv. Mater. 19, 553 (2007).Google Scholar
68.Li, W.J., Tuli, R., Huang, X., Laquerriere, P., Tuan, R.S., Biomater. 26, 5158 (2005).CrossRefGoogle Scholar
69.Jackman, R.J., Brittain, S.T., Adams, A., Prentiss, M.G., Whitesides, G.M., Science 280, 2089 (1998).Google Scholar
70.Csucs, G., Michel, R., Lussi, J.W., Textor, M., Danuser, G., Biomaterials 24, 1713 (2003).CrossRefGoogle Scholar
71.Flaim, C.J., Chien, S., Bhatia, S.N., Nat. Methods 2, 119 (2005).Google Scholar
72.Moroni, L., Lee, L.P., J. Biomed. Mater. Res. A 88, 644 (2009).Google Scholar
73.Flemming, R.G., Murphy, C.J., Abrams, G.A., Goodman, S.L., Nealey, P.F., Biomaterials 20, 573 (1999).Google Scholar
74.Duncan, A.C., Rouais, F., Lazare, S., Bordenave, L., Baquey, C., Colloids Surf. 54, 150 (2007).Google Scholar
75.Dalby, M.J., Andar, A., Nag, A., Affrossman, S., Tare, R., McFarlane, S., Oreffo, R.O., J. R. Soc., Interface 5, 1055 (2008).Google Scholar
76. P. De Biase, Capanna, R., Injury 36 (Suppl. 3), S43 (2005).Google Scholar
77.Habibovic, P., de Groot, K., J. Tissue Eng. Regen. Med. 1, 25 (2007).Google Scholar
78.Habibovic, P., Yuan, H., van den Doel, M., Sees, T.M., van Blitterswijk, C.A., de Groot, K., J. Orthop. Res. 24, 867 (2006).Google Scholar
79.Anderson, D.G., Levenberg, S., Langer, R., Nat. Biotechnol. 22, 863 (2004).Google Scholar
80.Truckenmuller, R., Giselbrecht, S., van Blitterswijk, C., Dambrowsky, N., Gottwald, E., Mappes, T., Rolletschek, A., Saile, V., Trautmann, C., Weibezahn, K.F., Welle, A., Lab Chip 8, 1570 (2008).Google Scholar
81.Flaim, C.J., Teng, D., Chien, S., Bhatia, S.N., Stem Cells Dev. 17, 29 (2008).Google Scholar
82.Papenburg, B., Vogelaar, L., Bolhuis-Versteeg, L., Lammertink, R., Stamatialis, D., Wessling, M., Biomaterials 28, 1998 (2007).Google Scholar
83.Figallo, E., Flaibani, M., Zavan, B., Abatangelo, G., Elvassore, N., Biotechnol. Prog. 23, 210 (2007).Google Scholar
84.Choi, N.W., Cabodi, M., Held, B., Gleghorn, J.P., Bonassar, L.J., Stroock, A.D., Nat. Mater. 6, 908 (2007).Google Scholar
85.Rivron, N.C., Rouwkema, J., Truckenmuller, R., Karperien, M., De Boer, J., van Blitterswijk, C.A., Biomater. 30, 4851 (2009).Google Scholar
86.Groenendijk, M., Laser Technik Journal 3, 44 (2008).Google Scholar
87.Groenendijk, M., Meijer, J., Journal of Laser Applications 18, 227 (2006).Google Scholar