The Integrated Role of Biomaterials and Stem Cells in Vascular Regeneration

  • Guoming Sun
  • Sravanti Kusuma
  • Sharon GerechtEmail author
Part of the Studies in Mechanobiology, Tissue Engineering and Biomaterials book series (SMTEB, volume 2)


A healthy vascular system is essential for maintaining normal blood supply and circulation in the body, while ischemia can lead to limb amputation or even death. Vascular regeneration engineering holds the promise of permanent, effective treatments for many vascular diseases. However, many challenges also remain to bring the therapy to the clinic, as the formation of blood vessels is a complicated process. One major challenge facing vascular engineering is developing the ability to maintain large masses of viable and functional cells during in vitro culture and following their transfer from in vitro conditions into the patient. This chapter introduces the cells being studied for vascular differentiation and regeneration and introduces the biomaterials being investigated for vascular engineering, including their sources, properties, and different scaffold types. We then discuss recent approaches to engineering microenvironments, including proper signaling cues and biodegradable scaffolds that will guide the development of these cells into vessels suitable for cell-based vascular therapy. These functional biomaterials may be used as environments to stimulate the generation of blood vessels, to deliver cells to angiogenic areas of the vasculature, or to promote differentiation from progenitor cells into mature vascular cells.


Hyaluronic Acid Endothelial Progenitor Cell Electrospun Fiber Vascular Regeneration Polymeric Scaffold 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. 1.
    Sun, G., Gerecht, S.: Vascular regeneration: engineering the stem cell microenvironment. Regener. Med. 4(3), 435–447 (2009)Google Scholar
  2. 2.
    Sata, M., Nagai, R.: Vascular regeneration and remodeling by circulating progenitor cells. In: Cardiovascular Regeneration Therapies Using Tissue Engineering Approaches, pp. 117–127. Springer, Tokyo (2005)Google Scholar
  3. 3.
    Asahara, T., Murohara, T., Sullivan, A., Silver, M., van der Zee, R., Li, T., Witzenbichler, B., Schatteman, G., Isner, J.M.: Isolation of putative progenitor endothelial cells for angiogenesis. Science 275(5302), 964–966 (1997)Google Scholar
  4. 4.
    Ferreira, L.S., Gerecht, S., Shieh, H.F., Watson, N., Rupnick, M.A., Dallabrida, S.M., Vunjak-Novakovic, G., Langer, R.: Vascular progenitor cells isolated from human embryonic stem cells give rise to endothelial and smooth muscle like cells and form vascular networks in vivo. Circ. Res. 101(3), 286–294 (2007)Google Scholar
  5. 5.
    Wagenseil, J.E., Mecham, R.P.: Vascular extracellular matrix and arterial mechanics. Physiol. Rev. 89(3), 957–989 (2009)Google Scholar
  6. 6.
    Galis, Z.S., Khatri, J.J.: Matrix metalloproteinases in vascular remodeling and atherogenesis: the good, the bad, and the ugly. Circ. Res. 90(3), 251–262 (2002)Google Scholar
  7. 7.
    Baluk, P., Hashizume, H., McDonald, D.M.: Cellular abnormalities of blood vessels as targets in cancer. Curr. Opin. Genet. Dev. 15(1), 102–111 (2005)Google Scholar
  8. 8.
    Davis, G.E., Senger, D.R.: Endothelial extracellular matrix: biosynthesis, remodeling, and functions during vascular morphogenesis and neovessel stabilization. Circ. Res. 97(11), 1093–1107 (2005)Google Scholar
  9. 9.
    Li, J., Zhang, Y.-P., Kirsner, R.S.: Angiogenesis in wound repair: angiogenic growth factors and the extracellular matrix. Microsc. Res. Tech. 60(1), 107–114 (2003)Google Scholar
  10. 10.
    Stupack, D.G., Cheresh, D.A., Gerald, P.S.: Integrins and angiogenesis. Curr. Top. Dev. Biol. 64, 207–238 (2004)Google Scholar
  11. 11.
    Wijelath, E.S., Rahman, S., Murray, J., Patel, Y., Savidge, G., Sobel, M.: Fibronectin promotes VEGF-induced CD34+ cell differentiation into endothelial cells. J. Vasc. Surg. 39(3), 655–660 (2004)Google Scholar
  12. 12.
    Stupack, D.G., Cheresh, D.A.: ECM remodeling regulates angiogenesis: endothelial integrins look for new ligands. Sci. STKE 2002(119), pe7 (2002)Google Scholar
  13. 13.
    Silva, E.A., Kim, E.-S., Kong, H.J., Mooney, D.J.: Material-based deployment enhances efficacy of endothelial progenitor cells. Proc. Natl. Acad. Sci. USA 105(38), 14347–14352 (2008)Google Scholar
  14. 14.
    Risau, W., Flamme, I.: Vasculogenesis. Ann. Rev. Cell Dev. Biol. 11(1), 73–91 (1995)Google Scholar
  15. 15.
    Carmeliet, P.: Mechanisms of angiogenesis and arteriogenesis. Nat. Med. 6(4), 389–395 (2000)Google Scholar
  16. 16.
    Thomson, J.A., Itskovitz-Eldor, J., Shapiro, S.S., Waknitz, M.A., Swiergiel, J.J., Marshall, V.S., Jones, J.M.: Embryonic stem cell lines derived from human blastocysts. Science 282(5391), 1145–1147 (1998)Google Scholar
  17. 17.
    Ferreira, L.S., Gerecht, S., Fuller, J., Shieh, H.F., Vunjak-Novakovic, G., Langer, R.: Bioactive hydrogel scaffolds for controllable vascular differentiation of human embryonic stem cells. Biomaterials 28(17), 2706–2717 (2007)Google Scholar
  18. 18.
    Hanjaya-Putra, D., Gerecht, S.: Vascular engineering using human embryonic stem cells. Biotechnol. Prog. 25(1), 2–9 (2009)Google Scholar
  19. 19.
    Levenberg, S., Zoldan, J., Basevitch, Y., Langer, R.: Endothelial potential of human embryonic stem cells. Blood 110(3), 806–814 (2007)Google Scholar
  20. 20.
    Shalaby, F., Rossant, J., Yamaguchi, T.P., Gertsenstein, M., Wu, X.F., Breitman, M.L., Schuh, A.C.: Failure of blood-island formation and vasculogenesis in FLK-1-deficient mice. Nature 376(6535), 62–66 (1995)Google Scholar
  21. 21.
    Ferrara, N., Carver-Moore, K., Chen, H., Dowd, M., Lu, L., O’Shea, K.S., Powell-Braxton, L., Hillan, K.J., Moore, M.W.: Heterozygous embryonic lethality induced by targeted inactivation of the VEGF gene. Nature 380(6573), 439–442 (1996)Google Scholar
  22. 22.
    Levenberg, S., Golub, J.S., Amit, M., Itskovitz-Eldor, J., Langer, R.: Endothelial cells derived from human embryonic stem cells. Proc. Natl. Acad. Sci. USA 99(7), 4391–4396 (2002)Google Scholar
  23. 23.
    Marchetti, S., Gimond, C., Iljin, K., Bourcier, C., Alitalo, K., Pouyssegur, J., Pages, G.: Endothelial cells genetically selected from differentiating mouse embryonic stem cells incorporate at sites of neovascularization in vivo. J. Cell Sci. 115(10), 2075–2085 (2002)Google Scholar
  24. 24.
    Cao, F., Lin, S., Xie, X., Ray, P., Patel, M., Zhang, X., Drukker, M., Dylla, S.J., Connolly, A.J., Chen, X., Weissman, I.L., Gambhir, S.S., Wu, J C.: In vivo visualization of embryonic stem cell survival, proliferation, and migration after cardiac delivery. Circulation 113(7), 1005–1014 (2006)Google Scholar
  25. 25.
    Gerecht-Nir, S., Ziskind, A., Cohen, S., Itskovitz-Eldor, J.: Human embryonic stem cells as an in vitro model for human vascular development and the induction of vascular differentiation. Lab. Invest. 83(12), 1811–1820 (2003)Google Scholar
  26. 26.
    Kaufman, D.S., Lewis, R.L., Hanson, E.T., Auerbach, R., Plendl, J., Thomson, J.A.: Functional endothelial cells derived from rhesus monkey embryonic stem cells. Blood 103(4), 1325–1332 (2004)Google Scholar
  27. 27.
    Vodyanik, M.A., Slukvin, I.I.: Hematoendothelial differentiation of human embryonic stem cells. In: Juan, S.B et al. (eds.) Current Protocols in Cell Biology, Chap. 23. Wiley, New York (2007)Google Scholar
  28. 28.
    Yamashita, J., Itoh, H., Hirashima, M., Kubo, H., Yurugi, T., Ogawa, M., Naito, M., Nakao, K., Nishikawa, S.: Identification of vascular progenitor cells in ES cells and vascular regeneration. J. Hypertens. 18, S189 (2000)Google Scholar
  29. 29.
    Narazaki, G., Uosaki, H., Teranishi, M., Okita, K., Kim, B., Matsuoka, S., Yamanaka, S., Yamashita, J.K.: Directed and systematic differentiation of cardiovascular cells from mouse induced pluripotent stem cells. Circulation 118(5), 498–506 (2008)Google Scholar
  30. 30.
    Sone, M., Itoh, H., Yamahara, K., Yamashita, J.K., Yurugi-Kobayashi, T., Nonoguchi, A., Suzuki, Y., Chao, T.H., Sawada, N., Fukunaga, Y., Miyashita, K., Park, K., Oyamada, N., Sawada, N., Taura, D., Tamura, N., Kondo, Y., Nito, S., Suemori, H., Nakatsuji, N., Nishikawa, S.I., Nakao, K.: Pathway for differentiation of human embryonic stem cells to vascular cell components and their potential for vascular regeneration. Arterioscler. Thromb. Vasc. Biol. 27(10), 2127–2134 (2007)Google Scholar
  31. 31.
    Taura, D., Sone, M., Homma, K., Oyamada, N., Takahashi, K., Tamura, N., Yamanaka, S., Nakao, K.: Induction and isolation of vascular cells from human induced pluripotent stem cells—brief report. Arterioscler. Thromb. Vasc. Biol. 29(7), 1100–1103 (2009)Google Scholar
  32. 32.
    Huang, H., Zhao, X., Chen, L., Xu, C., Yao, X., Lu, Y., Dai, L., Zhang, M.: Differentiation of human embryonic stem cells into smooth muscle cells in adherent monolayer culture. Biochem. Biophys. Res. Commun. 351(2), 321–327 (2006)Google Scholar
  33. 33.
    Xie, C.-Q., Huang, H., Wei, S., Song, L.-S., Zhang, J., Ritchie, R.P., Chen, L., Zhang, M., Chen, Y.E.: A comparison of murine smooth muscle cells generated from embryonic versus induced pluripotent stem cells. Stem Cells Dev. 18(5), 741–748 (2009)Google Scholar
  34. 34.
    Xiao, Q., Luo, Z., Pepe, A.E., Margariti, A., Zeng, L., Xu, Q.: Embryonic stem cell differentiation into smooth muscle cells is mediated by Nox4-produced H2O2. Am. J. Phys. Cell Physiol. 296(4) (2009)Google Scholar
  35. 35.
    Sinha, S., Wamhoff, B.R., Hoofnagle, M.H., Thomas, J., Neppl, R.L., Deering, T., Helmke, B.P., Bowles, D.K., Somlyo, A.V., Owens, G.K.: Assessment of contractility of purified smooth muscle cells derived from embryonic stem cells. Stem Cells 24(7), 1678–1688 (2006)Google Scholar
  36. 36.
    Riha, G.M., Wang, X., Wang, H., Chai, H., Mu, H., Lin, P.H., Lumsden, A.B., Yao, Q., Chen, C.: Cyclic strain induces vascular smooth muscle cell differentiation from murine embryonic mesenchymal progenitor cells. Surgery 141(3), 394–402 (2007)Google Scholar
  37. 37.
    Shintani, S., Murohara, T., Ikeda, H., Ueno, T., Honma, T., Katoh, A., Sasaki, K.-I., Shimada, T., Oike, Y., Imaizumi, T.: Mobilization of endothelial progenitor cells in patients with acute myocardial infarction. Circulation 103(23), 2776–2779 (2001)Google Scholar
  38. 38.
    Takahashi, T., Kalka, C., Masuda, H., Chen, D., Silver, M., Kearney, M., Magner, M., Isner, J.M., Asahara, T.: Ischemia- and cytokine-induced mobilization of bone marrow-derived endothelial progenitor cells for neovascularization. Nat. Med. 5(4), 434–438 (1999)Google Scholar
  39. 39.
    Lee, S.T., Chu, K., Jung, K.H., Park, H.K., Kim, D.H., Bahn, J.J., Kim, J.H., Oh, M.J., Lee, S.K., Kim, M., Roh, J.K.: Reduced circulating angiogenic cells in Alzheimer disease. Neurology 72(21), 1858–1863 (2009)Google Scholar
  40. 40.
    Tepper, O.M., Galiano, R.D., Capla, J.M., Kalka, C., Gagne, P.J., Jacobowitz, G.R., Levine, J.P., Gurtner, G.C.: Human endothelial progenitor cells from type II diabetics exhibit impaired proliferation, adhesion, and incorporation into vascular structures. Circulation 106 (22), 2781–2786 (2002)Google Scholar
  41. 41.
    Dzau, V.J., Gnecchi, M., Pachori, A.S., Morello, F., Melo, L.G.: Therapeutic potential of endothelial progenitor cells in cardiovascular diseases. Hypertension 46(1), 7–18 (2005)Google Scholar
  42. 42.
    Hill, J.M., Zalos, G., Halcox, J.P.J., Schenke, W.H., Waclawiw, M.A., Quyyumi, A.A., Finkel, T.: Circulating endothelial progenitor cells, vascular function, and cardiovascular risk. N. Engl. J. Med. 348(7), 593–600 (2003)Google Scholar
  43. 43.
    Mead, L.E., Prater, D., Yoder, M.C., Ingram, D.A.: Isolation and characterization of endothelial progenitor cells from human blood. Curr. Protoc. Stem Cell Biol. 6, 2C.1.1.–2C.1.27 (2008)Google Scholar
  44. 44.
    Broxmeyer, H.E., Srour, E., Orschell, C., Ingram, D.A., Cooper, S., Plett, P.A., Mead, L.E., Yoder, M.C.:Cord blood-derived stem and progenitor cells. In: Klimanskaya, I., Lanza, R. (eds.) Methods in Enzymology, vol. 419, pp. 439–473. Academic Press/Elsevier Science, San Diego (2006)Google Scholar
  45. 45.
    Vittet, D., Prandini, M.H., Berthier, R., Schweitzer, A., Martin-Sisteron, H., Uzan, G., Dejana, E.: Embryonic stem cells differentiate in vitro to endothelial cells through successive maturation steps. Blood 88(9), 3424–3431 (1996)Google Scholar
  46. 46.
    Choi, K.-D., Junying, Y., Kim, S.-O., Giorgia, S., William, R., Maxim, V., James, T., Igor, S.: Hematopoietic and endothelial differentiation of human induced pluripotent stem cells. Stem Cells 27(3), 559–567 (2009)Google Scholar
  47. 47.
    Ross, R.: Atherosclerosis—an inflammatory disease. N. Engl. J. Med. 340(2), 115–126 (1999)Google Scholar
  48. 48.
    Blank, R.S., Swartz, E.A., Thompson, M.M., Olson, E.N., Owens, G.K.: A retinoic acid-induced clonal cell line derived from multipotential P19 embryonal carcinoma cells expresses smooth muscle characteristics. Circ. Res. 76(5), 742–749 (1995)Google Scholar
  49. 49.
    Van Tomme, S.R., Hennink, W.E.: Biodegradable dextran hydrogels for protein delivery applications. Expert Rev. Med. Dev. 4(2), 147–164 (2007)Google Scholar
  50. 50.
    Weinberg, C.B., Bell, E.: A blood vessel model constructed from collagen and cultured vascular cells. Science 231(4736), 397–400 (1986)Google Scholar
  51. 51.
    Thomas, V., Zhang, X., Catledge, S.A., Vohra, Y.K.: Functionally graded electrospun scaffolds with tunable mechanical properties for vascular tissue regeneration. Biomed. Mater. 2(4), 224–232 (2007)Google Scholar
  52. 52.
    He, W., Yong, T., Ma, Z.W., Inai, R., Teo, W.E., Ramakrishna, S.: Biodegradable polymer nanofiber mesh to maintain functions of endothelial cells. Tissue Eng. 12(9), 2457–2466 (2006)Google Scholar
  53. 53.
    Swartz, D.D., Russell, J.A., Andreadis, S.T.: Engineering of fibrin-based functional and implantable small-diameter blood vessels. Am. J. Physiol. Heart Circ. Physiol. 288(3), H1451–H1460 (2005)Google Scholar
  54. 54.
    Beamish, J.A., Fu, A.Y., Choi, A.-J., Haq, N.A., Kottke-Marchant, K., Marchant, R.E.: The influence of RGD-bearing hydrogels on the re-expression of contractile vascular smooth muscle cell phenotype. Biomaterials 30(25), 4127–4135 (2009)Google Scholar
  55. 55.
    Freeman, I., Cohen, S.: The influence of the sequential delivery of angiogenic factors from affinity-binding alginate scaffolds on vascularization. Biomaterials 30(11), 2122–2131 (2009)Google Scholar
  56. 56.
    Kedem, A., Perets, A., Gamlieli-Bonshtein, I., Dvir-Ginzberg, M., Mizrahi, S., Cohen, S.: Vascular endothelial growth factor-releasing scaffolds enhance vascularization and engraftment of hepatocytes transplanted on liver lobes. Tissue Eng. 11(5–6), 715–722 (2005)Google Scholar
  57. 57.
    Loebsack, A., Greene, K., Wyatt, S., Culberson, C., Austin, C., Beiler, R., Roland, W., Eiselt, P., Rowley, J., Burg, K., Mooney, D., Holder, W., Halberstadt, C.: In vivo characterization of a porous hydrogel material for use as a tissue bulking agent. J. Biomed. Mater. Res. 57(4), 575–581 (2001)Google Scholar
  58. 58.
    Gerecht-Nir, S., Cohen, S., Ziskind, A., Itskovitz-Eldor, J.: Three-dimensional porous alginate scaffolds provide a conducive environment for generation of well-vascularized embryoid bodies from human embryonic stem cells. Biotechnol. Bioeng. 88(3), 313–320 (2004)Google Scholar
  59. 59.
    Chupa, J.M., Foster, A.M., Sumner, S.R., Madihally, S.V., Matthew, H.W.T.: Vascular cell responses to polysaccharide materials: in vitro and in vivo evaluations. Biomaterials 21(22), 2315–2322 (2000)Google Scholar
  60. 60.
    Sun, G., Chu, C.-C.: Synthesis, characterization of biodegradable dextran-allyl isocyanate-ethylamine/polyethylene glycol-diacrylate hydrogels and their in vitro release of albumin. Carbohydr. Polym. 65(3), 273–287 (2006)Google Scholar
  61. 61.
    Stephen, P., Massia, J.S.: Immobilized RGD peptides on surface-grafted dextran promote biospecific cell attachment. J. Biomed. Mater. Res. 56(3), 390–399 (2001)Google Scholar
  62. 62.
    Sun, G., Shen, Y.I., Ho, C.C., Kusuma, S., Gerecht, S.: Functional groups affect physical and biological properties of dextran-based hydrogels. J. Biomed. Mater. Res. Part A 9999 (9999), NA (2009)Google Scholar
  63. 63.
    Peattie, R.A., Nayate, A.P., Firpo, M.A., Shelby, J., Fisher, R.J., Prestwich, G.D.: Stimulation of in vivo angiogenesis by cytokine-loaded hyaluronic acid hydrogel implants. Biomaterials 25(14), 2789–2798 (2004)Google Scholar
  64. 64.
    Giavaresi, G., Torricelli, P., Fornasari, P.M., Giardino, R., Barbucci, R., Leone, G.: Blood vessel formation after soft-tissue implantation of hyaluronanbased hydrogel supplemented with copper ions. Biomaterials 26(16), 3001–3008 (2005)Google Scholar
  65. 65.
    Slevin, M., Krupinski, J., Kumar, S., Gaffney, J.: Angiogenic oligosaccharides of hyaluronan induce protein tyrosine kinase activity in endothelial cells and activate a cytoplasmic signal transduction pathway resulting in proliferation. Lab. Invest. 78(8), 987–1003 (1998)Google Scholar
  66. 66.
    Gerecht, S., Burdick, J.A., Ferreira, L.S., Townsend, S.A., Langer, R., Vunjak-Novakovic, G.: Hyaluronic acid hydrogel for controlled self-renewal and differentiation of human embryonic stem cells. Proc. Natl. Acad. Sci. USA 104(27), 11298–11303 (2007)Google Scholar
  67. 67.
    Autissier, A., Letourneur, D., Visage, C.L.: Pullulan-based hydrogel for smooth muscle cell culture. J. Biomed. Mater. Res. Part A 82A(2), 336–342 (2007)Google Scholar
  68. 68.
    Koch, S., Yao, C., Grieb, G., Prevel, P., Noah, E.M., Steffens, G.C.M.: Enhancing angiogenesis in collagen matrices by covalent incorporation of VEGF. J. Mater. Sci. Mater. Med. 17(8), 735–741 (2006)Google Scholar
  69. 69.
    Matthews, J.A., Wnek, G.E., Simpson, D.G., Bowlin, G.L.: Electrospinning of collagen nanofibers. Biomacromolecules 3(2), 232–238 (2002)Google Scholar
  70. 70.
    Matthews, J.A., Boland, E.D., Wnek, G.E., Simpson, D.G., Bowlin, G.L.: Electrospinning of collagen type II: a feasibility study. J. Bioact. Compat. Polym. 18(2), 125–134 (2003).Google Scholar
  71. 71.
    Shaikh, F.M., Callanan, A., Kavanagh, E.G., Burke, P.E., Grace, P.A., McGloughlin, T.M.: Fibrin: a natural biodegradable scaffold in vascular tissue engineering. Cells Tissues Organs 188(4), 333–346 (2008)Google Scholar
  72. 72.
    Jin, H.J., Chen, J.S., Karageorgiou, V., Altman, G.H., Kaplan, D.L.: Human bone marrow stromal cell responses on electrospun silk fibroin mats. Biomaterials 25(6), 1039–1047 (2004)Google Scholar
  73. 73.
    Soffer, L., Wang, X.Y., Mang, X.H., Kluge, J., Dorfmann, L., Kaplan, D.L., Leisk, G.: Silk-based electrospun tubular scaffolds for tissue-engineered vascular grafts. J. Biomater. Sci. Polym. Ed. 19(5), 653–664 (2008)Google Scholar
  74. 74.
    Jin, H.J., Fridrikh, S.V., Rutledge, G.C., Kaplan, D.L.: Electrospinning Bombyx mori silk with poly(ethylene oxide). Biomacromolecules 3(6), 1233–1239 (2002)Google Scholar
  75. 75.
    Silva, E.A., Mooney, D.J.: Spatiotemporal control of vascular endothelial growth factor delivery from injectable hydrogels enhances angiogenesis. J. Thromb. Haem. 5(3), 590–598 (2007)Google Scholar
  76. 76.
    Chenite, A., Chaput, C., Wang, D., Combes, C., Buschmann, M.D., Hoemann, C.D., Leroux, J.C., Atkinson, B.L., Binette, F., Selmani, A.: Novel injectable neutral solutions of chitosan form biodegradable gels in situ. Biomaterials 21(21), 2155–2161 (2000)Google Scholar
  77. 77.
    Ishihara, M., Obara, K., Ishizuka, T., Fujita, M., Sato, M., Masuoka, K., Saito, Y., Yura, H., Matsui, T., Hattori, H., Kikuchi, M., Kurita, A.: Controlled release of fibroblast growth factors and heparin from photocrosslinked chitosan hydrogels and subsequent effect on in vivo vascularization. J. Biomed. Mater. Res. Part A 64A(3), 551–559 (2003)Google Scholar
  78. 78.
    Bettinger, C.J., Bruggeman, J.P., Borenstein, J.T., Langer, R.S.: Amino alcohol-based degradable poly(ester amide) elastomers. Biomaterials 29(15), 2315–2325 (2008)Google Scholar
  79. 79.
    Yamanouchi, D., Wu, J., Lazar, A.N., Craig Kent, K., Chu, C.-C., Liu, B.: Biodegradable arginine-based poly(ester-amide)s as non-viral gene delivery reagents. Biomaterials 29(22), 3269–3277 (2008)Google Scholar
  80. 80.
    Levenberg, S., Huang, N.F., Lavik, E., Rogers, A.B., Itskovitz-Eldor, J., Langer, R.: Differentiation of human embryonic stem cells on three-dimensional polymer scaffolds. Proc. Natl. Acad. Sci. USA 100(22), 12741–12746 (2003)Google Scholar
  81. 81.
    Wang, G.J., Hsueh, C.C., Hsu, S.H., Hung, H.S.: Fabrication of PLGA microvessel scaffolds with circular microchannels using soft lithography. J. Micromech. Microeng. 17(10), 2000–2005 (2007)Google Scholar
  82. 82.
    Ma, Z.W., He, W., Yong, T., Ramakrishna, S.: Grafting of gelatin on electrospun poly(caprolactone) nanofibers to improve endothelial cell spreading and proliferation and to control cell orientation. Tissue Eng. 28(3), 1149–1158 (2005)Google Scholar
  83. 83.
    Williamson, M.R., Woollard, K.J., Griffiths, H.R., Coombes, A.G.A.: Gravity spun polycaprolactone fibers for applications in vascular tissue engineering: proliferation and function of human vascular endothelial cells. Tissue Eng. 12(1), 45–51 (2006)Google Scholar
  84. 84.
    Pankajakshan, D., Kalliyana, K., Krishnan, L.K.: Vascular tissue generation in response to signaling molecules integrated with a novel poly(epsilon-caprolactone)-fibrin hybrid scaffold. J. Tissue Eng. Regen. Med. 1(5), 389–397 (2007)Google Scholar
  85. 85.
    Sarkar, S., Lee, G.Y., Wong, J.Y., Desai, T.A.: Development and characterization of a porous micro-patterned scaffold for vascular tissue engineering applications. Biomaterials 27(27), 4775–4782 (2006)Google Scholar
  86. 86.
    Dong, Y.X., Yong, T., Liao, S., Chan, C.K., Ramakrishna, S.: Long-term viability of coronary artery smooth muscle cells on poly(l-lactide-co-epsilon-caprolactone) nanofibrous scaffold indicates its potential for blood vessel tissue engineering. J. R. Soc. Interface 5(26), 1109–1118 (2008)Google Scholar
  87. 87.
    Hemmrich, K., Salber, J., Meersch, M., Wiesemann, U., Gries, T., Pallua, N., Klee, D.: Three-dimensional nonwoven scaffolds from a novel biodegradable poly(ester amide) for tissue engineering applications. J. Mater. Sci. Mater. Med. 19(1), 257–267 (2008)Google Scholar
  88. 88.
    Nijst, C.L.E., Bruggeman, J.P., Karp, J.M., Ferreira, L., Zumbuehl, A., Bettinger, C.J., Langer, R.: Synthesis and characterization of photocurable elastomers from poly(glycerol-co-sebacate). Biomacromolecules 8(10), 3067–3073 (2007)Google Scholar
  89. 89.
    Gerecht, S., Townsend, S.A., Pressler, H., Zhu, H., Nijst, C.L.E., Bruggeman, J.P., Nichol, J.W., Langer, R.: A porous photocurable elastomer for cell encapsulation and culture. Biomaterials 28(32), 4826–4835 (2007)Google Scholar
  90. 90.
    Yang, F., Cho, S.-W.C., Son, S.M., Bogatyrev, S.R., Singh, D., Green, J.J., Mei, Y., Park, S., Bhang, S.H., Kim, B.-S., Langer, R., Anderson, D.G.: Genetic engineering of human stem cells for enhanced angiogenesis using biodegradable polymeric nanoparticles. Proc. Natl. Acad. Sci. USA 107(8) 3317–3322 (2009)Google Scholar
  91. 91.
    Richardson, T.P., Peters, M.C., Ennett, A.B., Mooney, D.J.: Polymeric system for dual growth factor delivery. Nat. Biotech. 19(11), 1029–1034 (2001)Google Scholar
  92. 92.
    Zong, X., Bien, H., Chung, C.-Y., Yin, L., Fang, D., Hsiao, B.S., Chu, B., Entcheva, E.: Electrospun fine-textured scaffolds for heart tissue constructs. Biomaterials 26(26), 5330–5338 (2005)Google Scholar
  93. 93.
    Xu, C.Y., Inai, R., Kotaki, M., Ramakrishna, S.: Aligned biodegradable nanofibrous structure: a potential scaffold for blood vessel engineering. Biomaterials 25(5), 877–886 (2004)Google Scholar
  94. 94.
    Yoshimoto, H., Shin, Y.M., Terai, H., Vacanti, J.P.: A biodegradable nanofiber scaffold by electrospinning and its potential for bone tissue engineering. Biomaterials 24(12), 2077–2082 (2003)Google Scholar
  95. 95.
    Shin, M., Yoshimoto, H., Vacanti, J.P.: In vivo bone tissue engineering using mesenchymal stem cells on a novel electrospun nanofibrous scaffold. Tissue Eng. 10(1–2), 33–41 (2004)Google Scholar
  96. 96.
    Davis, M.E., Motion, J.P.M., Narmoneva, D.A., Takahashi, T., Hakuno, D., Kamm, R.D., Zhang, S., Lee, R.T.: Injectable self-assembling peptide nanofibers create intramyocardial microenvironments for endothelial cells. Circulation 111(4), 442–450 (2005)Google Scholar
  97. 97.
    Ekaputra, A.K., Prestwich, G.D., Cool, S.M., Hutmacher, D.W.: Combining electrospun scaffolds with electrosprayed hydrogels leads to three-dimensional cellularization of hybrid constructs. Biomacromolecules 9(8), 2097–2103 (2008)Google Scholar
  98. 98.
    Kashyap, N., Kumar, N., Kumar, M.N.V.R.: Hydrogels for pharmaceutical and biomedical applications. 22(2), 107–150 (2005)Google Scholar
  99. 99.
    Jagur-Grodzinski, J.: Polymeric gels and hydrogels for biomedical and pharmaceutical applications. Polym. Adv. Technol. 9999(9999), n/a (2009)Google Scholar
  100. 100.
    Nicodemus, G.D., Bryant, S.J.: Cell encapsulation in biodegradable hydrogels for tissue engineering applications. Tissue Eng. Part B Rev. 14(2), 149–165 (2008)Google Scholar
  101. 101.
    Seliktar, D., Black, R.A., Vito, R.P., Nerem, R.M.: Dynamic mechanical conditioning of collagen-gel blood vessel constructs induces remodeling in vitro. Ann. Biomed. Eng. 28(4), 351–362 (2000)Google Scholar
  102. 102.
    Yamamoto, M., Ikada, Y., Tabata, Y.: Controlled release of growth factors based on biodegradation of gelatin hydrogel. J. Biomater. Sci. Polym. Ed. 12(1), 77–88 (2001)Google Scholar
  103. 103.
    Kraehenbuehl, T.P., Ferreira, L.S., Zammaretti, P., Hubbell, J.A., Langer, R.: Cell-responsive hydrogel for encapsulation of vascular cells. Biomaterials 30(26), 4318–4324 (2009)Google Scholar
  104. 104.
    Subbiah, T., Bhat, G.S., Tock, R.W., Parameswaran, S., Ramkumar, S.S.: Electrospinning of nanofibers. J. Appl. Polym. Sci. 96(2), 557–569 (2005)Google Scholar
  105. 105.
    Kidoaki, S., Kwon, I.K., Matsuda, T.: Mesoscopic spatial designs of nano- and microfiber meshes for tissue-engineering matrix and scaffold based on newly devised multilayering and mixing electrospinning techniques. Biomaterials 26(1), 37–46 (2005)Google Scholar
  106. 106.
    Yang, F., Murugan, R., Wang, S., Ramakrishna, S.: Electrospinning of nano/micro scale poly(l-lactic acid) aligned fibers and their potential in neural tissue engineering. Biomaterials 26(15), 2603–2610 (2005)Google Scholar
  107. 107.
    Stankus, J.J., Soletti, L., Fujimoto, K., Hong, Y., Vorp, D.A., Wagner, W.R.: Fabrication of cell microintegrated blood vessel constructs through electrohydrodynamic atomization. Biomaterials 28(17), 2738–2746 (2007)Google Scholar
  108. 108.
    Jeong, S.I., Kim, S.Y., Cho, S.K., Chong, M.S., Kim, K.S., Kim, H., Lee, S.B., Lee, Y.M.: Tissue-engineered vascular grafts composed of marine collagen and PLGA fibers using pulsatile perfusion bioreactors. Biomaterials 28(6), 1115–1122 (2007)Google Scholar
  109. 109.
    Lee, S.J., Yoo, J.J., Lim, G.J., Atala, A., Stitze, J.: In vitro evaluation of electrospun nanofiber scaffolds for vascular graft application. J. Biomed. Mater. Res. A 83A(4), 999–1008 (2007)Google Scholar
  110. 110.
    Qi, H.X., Kong, S.L., Hu, P., Zhang, J., Lin, W.J., Song, F.: In: Kim, H.S., Li,Y.B., Lee, S.W. (eds.) Biomimic Tubulose Scaffolds with Multilayer Prepared by Electrospinning for Tissue Engineering, pp. 882–885. Trans Tech, Zurich (2006)Google Scholar
  111. 111.
    Pham, Q.P., Sharma, U., Mikos, A.G.: Electrospun poly(ε-caprolactone) microfiber and multilayer nanofiber/microfiber scaffolds:  characterization of scaffolds and measurement of cellular infiltration. Biomacromolecules 7(10), 2796–2805 (2006)Google Scholar
  112. 112.
    Zhang, D., Chang, J.: Electrospinning of three-dimensional nanofibrous tubes with controllable architectures. Nano Lett. 8(10), 3283–3287 (2008)Google Scholar
  113. 113.
    Park, T.G., Hoffman, A.S.: Synthesis and characterization of pH- and or temperature-sensitive hydrogels. J. Appl. Polym. Sci. 46(4), 659–671 (1992)Google Scholar
  114. 114.
    Sun, G.M., Zhang, X.Z., Chu, C.C.: Formulation and characterization of chitosan-based hydrogel films having both temperature and pH sensitivity. J. Mater. Sci. Mater. Med. 18(8), 1563–1577 (2007)Google Scholar
  115. 115.
    Klumb, L.A., Horbett, T.A.: Design of insulin delivery devices based on glucose sensitive membranes. J. Contr. Rel. 18(1), 59–80 (1992)Google Scholar
  116. 116.
    Moroni, L., De Wijn, J.R., Van Blitterswijk, C.A.: Integrating novel technologies to fabricate smart scaffolds. J. Biomater. Sci. Polym. Ed. 19(5), 543–572 (2008)Google Scholar
  117. 117.
    Sittinger, M., Hutmacher, D.W., Risbud, M.V.: Current strategies for cell delivery in cartilage and bone regeneration. Curr. Opin. Biotechnol. 15(5), 411–418 (2004)Google Scholar
  118. 118.
    Kloxin, A.M., Kasko, A.M., Salinas, C.N., Anseth, K.S.: Photodegradable hydrogels for dynamic tuning of physical and chemical properties. Science 324(5923), 59–63 (2009)Google Scholar
  119. 119.
    Khetan, S., Katz, J.S., Burdick, J.A.: Sequential crosslinking to control cellular spreading in 3-dimensional hydrogels. Soft Matter 5(8), 1601–1606 (2009)Google Scholar
  120. 120.
    Deutsch, J., Motlagh, D., Russell, B., Desai, T.A.: Fabrication of microtextured membranes for cardiac myocyte attachment and orientation. J. Biomed. Mater. Res. 53(3), 267–275 (2000)Google Scholar
  121. 121.
    Timpl, R.: Macromolecular organization of basement membranes. Curr. Opin. Cell Biol. 8(5), 618–624 (1996)Google Scholar
  122. 122.
    Abrams, G.A., Schaus, S.S., Goodman, S.L., Nealey, P.F., Murphy, C.J.: Nanoscale topography of the corneal epithelial basement membrane and Descemet’s membrane of the human. Cornea 19(1), 57–64 (2000)Google Scholar
  123. 123.
    Watt, F.M., Jordan, P.W., O’Neill, C.H.: Cell shape controls terminal differentiation of human epidermal keratinocytes. Proc. Natl. Acad. Sci. USA 85(15), 5576–5580 (1988)Google Scholar
  124. 124.
    McBeath, R., Pirone, D.M., Nelson, C.M., Bhadriraju, K., Chen, C.S.: Cell shape, cytoskeletal tension, and RhoA regulate stem cell lineage commitment. Dev. Cell 6(4), 483–495 (2004)Google Scholar
  125. 125.
    Yim, E.K., Reano, R.M., Pang, S.W., Yee, A.F., Chen, C.S., Leong, K.W.: Nanopattern-induced changes in morphology and motility of smooth muscle cells. Biomaterials 26(26), 5405–5413 (2005)Google Scholar
  126. 126.
    Pasqui, D., Rossi, A., Barbucci, R., Lamponi, S., Gerli, R., Weber, E.: Hyaluronan and sulphated hyaluronan micropatterns: effect of chemical and topographic cues on lymphatic endothelial cell alignment and proliferation. Lymphology 38(2), 50–65 (2005)Google Scholar
  127. 127.
    Rossi, A., Pasqui, D., Barbucci, R., Gerli, R., Weber, E.: The topography of microstructured surfaces differently affects fibrillin deposition by blood and lymphatic endothelial cells in culture. Tissue Eng. Part A 15(3), 525–533 (2009)Google Scholar
  128. 128.
    Bettinger, C.J., Zhang, Z., Gerecht, S., Borenstein, J.T., Langer, R.: Enhancement of in vitro capillary tube formation by substrate nanotopography. Adv. Mater. 20(1), 99–103 (2008)Google Scholar
  129. 129.
    Kim, B.S., Nikolovski, J., Bonadio, J., Mooney, D.J.: Cyclic mechanical strain regulates the development of engineered smooth muscle tissue. Nat. Biotechnol. 17(10), 979–983 (1999)Google Scholar
  130. 130.
    Nerem, R.M.: Vascular fluid mechanics, the arterial wall, and atherosclerosis. J. Biomech. Eng. 114(3), 274–282 (1992)Google Scholar
  131. 131.
    Mo, M., Eskin, S.G., Schilling, W.P.: Flow-induced changes in Ca2+ signaling of vascular endothelial cells: effect of shear–stress and ATP. Am. J. Physiol. 260(5), H1698-H1707 (1991)Google Scholar
  132. 132.
    De Keulenaer, G.W., Chappell, D.C., Ishizaka, N., Nerem, R.M., Alexander, R.W., Griendling, K.K.: Oscillatory and steady laminar shear stress differentially affect human endothelial redox state—role of a superoxide-producing NADH oxidase. Circ. Res. 82(10), 1094–1101 (1998)Google Scholar
  133. 133.
    Shyy, J.Y., Chien, S.: Role of integrins in endothelial mechanosensing of shear stress. Circ. Res. 91(9), 769–775 (2002)Google Scholar
  134. 134.
    Stone, P.H., Coskun, A.U., Kinlay, S., Clark, M.E., Sonka, M., Wahle, A., Ilegbusi, O.J., Yeghiazarians, Y., Popma, J.J., Orav, J., Kuntz, R.E., Feldman, C.L.: Effect of endothelial shear stress on the progression of coronary artery disease, vascular remodeling, and in-stent restenosis in humans—in vivo 6-month follow-up study. Circulation 108(4), 438–444 (2003)Google Scholar
  135. 135.
    Huang, H., Nakayama, Y., Qin, K., Yamamoto, K., Ando, J., Yamashita, J., Itoh, H., Kanda, K., Yaku, H., Okamoto, Y., Nemoto, Y.: Differentiation from embryonic stem cells to vascular wall cells under in vitro pulsatile flow loading. J. Art. Org. 8(2), 110–118 (2005)Google Scholar
  136. 136.
    Wang, H., Riha, G.M., Yan, S., Li, M., Chai, H., Yang, H., Yao, Q., Chen, C.: Shear stress induces endothelial differentiation from a murine embryonic mesenchymal progenitor cell line. Arterioscler. Thromb. Vasc. Biol. 25(9), 1817–1823 (2005)Google Scholar
  137. 137.
    Illi, B., Scopece, A., Nanni, S., Farsetti, A., Morgante, L., Biglioli, P., Capogrossi, M.C., Gaetano, C.: Epigenetic histone modification and cardiovascular lineage programming in mouse embryonic stem cells exposed to laminar shear stress. Circ. Res. 96(5), 501–508 (2005)Google Scholar
  138. 138.
    Zeng, L.F., Xiao, Q.Z., Margariti, A., Zhang, Z.Y., Zampetaki, A., Patel, S., Capogrossi, M.C., Hu, Y.H., Xu, Q.B.: HDAC3 is crucial in shear- and VEGF-induced stem cell differentiation toward endothelial cells. J. Cell Biol. 174(7), 1059–1069 (2006)Google Scholar
  139. 139.
    Metallo, C.M., Vodyanik, M.A., Pablo, J.J.D., Slukvin, I.I., Palecek, S.P.: The response of human embryonic stem cell-derived endothelial cells to shear stress. Biotechnol. Bioeng. 100(4), 830–837 (2008)Google Scholar
  140. 140.
    Ye, C., Bai, L., Yan, Z.Q., Wang, Y.H., Jiang, Z.L.: Shear stress and vascular smooth muscle cells promote endothelial differentiation of endothelial progenitor cells via activation of Akt. Clin. Biomech.23, S118-S124 (2008)Google Scholar
  141. 141.
    Kasper, G., Dankert, N., Tuischer, J., Hoeft, M., Gaber, T., Glaeser, J.D., Zander, D., Tschirschmann, M., Thompson, M., Matziolis, G., Duda, G.N.: Mesenchymal stem cells regulate angiogenesis according to their mechanical environment. Stem Cells 25(4), 903–910 (2007)Google Scholar
  142. 142.
    Gong, Z.D., Niklason, L.E.: Small-diameter human vessel wall engineered from bone marrow-derived mesenchymal stem cells (hMSCs). FASEB J. 22(6), 1635–1648 (2008)Google Scholar
  143. 143.
    Wu, X., Rabkin-Aikawa, E., Guleserian, K.J., Perry, T.E., Masuda, Y., Sutherland, F.W.H., Schoen, F.J., Mayer, J.E., Jr, Bischoff, J.: Tissue-engineered microvessels on three-dimensional biodegradable scaffolds using human endothelial progenitor cells. Am. J. Physiol. Heart Circ. Physiol. 287(2), H480–H487 (2004)Google Scholar
  144. 144.
    Hiraoka, N., Allen, E., Apel, I.J., Gyetko, M.R., Weiss, S.J.: Matrix metalloproteinases regulate neovascularization by acting as pericellular fibrinolysins. 95(3), 365–377 (1998)Google Scholar
  145. 145.
    Cao, L., Arany, P.R., Wang, Y.S., Mooney, D.J.: Promoting angiogenesis via manipulation of VEGF responsiveness with notch signaling. Biomaterials 30(25), 4085–4093 (2009)Google Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2010

Authors and Affiliations

  1. 1.Departments of Chemical and Biomolecular EngineeringJohns Hopkins UniversityBaltimoreUSA
  2. 2.Department of Biomedical EngineeringJohns Hopkins UniversityBaltimoreUSA

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