Advertisement

Mechanical Regulation of Vascularization in Three-Dimensional Engineered Tissues

  • Barak Zohar
  • Shira Landau
  • Shulamit Levenberg
Chapter
Part of the Biological and Medical Physics, Biomedical Engineering book series (BIOMEDICAL)

Abstract

The vascularization of three-dimensional (3D) engineered tissues enhances their in vivo integration with the host vasculature and its ability to serve as sustainable biological substitutes for injured or sick tissues. Engineered vascular networks must comply with the corresponding host’s vasculature structure, which is known to be regulated by mechanical stimuli. The impact of mechanical cues on vascularization of 3D engineered constructs is gaining much attention, as they may allow for control of vascular network structure, directionality, remodeling, and maturation to ensure long-term functionality. Mechanical forces can be generated in vitro either by actively applying an external source of force or following internal induction by cellular contractile forces responding to the mechanical properties of the engineered construct. This chapter provides an overview of recent studies aimed to explore the impact of both internal and external mechanical stimulations on vascularization of 3D engineered tissues and will propose future directions to advance some of the current challenges.

Keywords

Endothelial cells Engineered tissue 3D culture Vascular networks Biomaterials Matrix Contractile force Tension and shear stress 

References

  1. 1.
    Ando, J., & Yamamoto, K. (2009). Vascular mechanobiology: Endothelial cell responses to fluid shear stress. Circulation Journal, 73, 1983–1992.CrossRefGoogle Scholar
  2. 2.
    Anisi, F., Salehi-Nik, N., Amoabediny, G., Pouran, B., Haghighipour, N., & Zandieh-Doulabi, B. (2014). Applying shear stress to endothelial cells in a new perfusion chamber: Hydrodynamic analysis. Journal of Artificial Organs, 17, 329–336.CrossRefGoogle Scholar
  3. 3.
    Bellan, L. M., Singh, S. P., Henderson, P. W., Porri, T. J., Craighead, H. G., & Spector, J. A. (2009). Fabrication of an artificial 3-dimensional vascular network using sacrificial sugar structures. Soft Matter, 5, 1354.ADSCrossRefGoogle Scholar
  4. 4.
    Beningo, K. A., Dembo, M., Kaverina, I., Small, J. V., & Wang, Y. L. (2001). Nascent focal adhesions are responsible for the generation of strong propulsive forces in migrating fibroblasts. The Journal of Cell Biology, 153, 881–888.CrossRefGoogle Scholar
  5. 5.
    Brown, A., Burke, G., & Meenan, B. J. (2011). Modeling of shear stress experienced by endothelial cells cultured on microstructured polymer substrates in a parallel plate flow chamber. Biotechnology and Bioengineering, 108, 1148–1158.CrossRefGoogle Scholar
  6. 6.
    Ceccarelli, J., Cheng, A., & Putnam, A. J. (2012). Mechanical strain controls endothelial patterning during angiogenic sprouting. Cellular and Molecular Bioengineering, 5, 463–473.CrossRefGoogle Scholar
  7. 7.
    Chang, C. C., Krishnan, L., Nunes, S. S., Church, K. H., Edgar, L. T., Boland, E. D., et al. (2012). Determinants of microvascular network topologies in implanted neovasculatures. Arteriosclerosis, Thrombosis, and Vascular Biology, 32, 5–14.CrossRefGoogle Scholar
  8. 8.
    De Smet, F., Segura, I., De Bock, K., Hohensinner, P. J., & Carmeliet, P. (2009). Mechanisms of vessel branching filopodia on endothelial tip cells lead the way. Arteriosclerosis, Thrombosis, and Vascular Biology, 29, 639–649.CrossRefGoogle Scholar
  9. 9.
    Edgar, L. T., Underwood, C. J., Guilkey, J. E., Hoying, J. B., & Weiss, J. A. (2014). Extracellular matrix density regulates the rate of neovessel growth and branching in sprouting angiogenesis. PLoS One, 9, e85178.ADSCrossRefGoogle Scholar
  10. 10.
    Engler, A. J., Sen, S., Sweeney, H. L., & Discher, D. E. (2006). Matrix elasticity directs stem cell lineage specification. Cell, 126, 677–689.CrossRefGoogle Scholar
  11. 11.
    Fish, J. E., Santoro, M. M., Morton, S. U., Yu, S., Yeh, R.-F., Wythe, J. D., et al. (2008). miR-126 regulates angiogenic signaling and vascular integrity. Dev. Cell, 15, 272–284.Google Scholar
  12. 12.
    Francis-Sedlak, M. E., Moya, M. L., Huang, J.-J., Lucas, S. A., Chandrasekharan, N., Larson, J. C., et al. (2010). Collagen glycation alters neovascularization in vitro and in vivo. Microvascular Research, 80, 3–9.CrossRefGoogle Scholar
  13. 13.
    Galie, P. A., Nguyen, D.-H. T., Choi, C. K., Cohen, D. M., Janmey, P. A., & Chen, C. S. (2014). Fluid shear stress threshold regulates angiogenic sprouting. Proceedings of the National Academy of Sciences of the United States of America, 111, 7968–7973.ADSCrossRefGoogle Scholar
  14. 14.
    Gassman, A. A., Kuprys, T., Ucuzian, A. A., Brey, E., Matsumura, A., Pang, Y., et al. (2011). Three-dimensional 10% cyclic strain reduces bovine aortic endothelial cell angiogenic sprout length and augments tubulogenesis in tubular fibrin hydrogels. Journal of Tissue Engineering and Regenerative Medicine, 5, 375–383.CrossRefGoogle Scholar
  15. 15.
    Gee, E., Milkiewicz, M., & Haas, T. L. (2010). p38 MAPK activity is stimulated by vascular endothelial growth factor receptor 2 activation and is essential for shear stress-induced angiogenesis. Journal of Cellular Physiology, 222, 120–126.CrossRefGoogle Scholar
  16. 16.
    Ghajar, C. M., Chen, X., Harris, J. W., Suresh, V., Hughes, C. C. W., Jeon, N. L., et al. (2008). The effect of matrix density on the regulation of 3-D capillary morphogenesis. Biophysical Journal, 94, 1930–1941.ADSCrossRefGoogle Scholar
  17. 17.
    Helm, C.-L. E., Zisch, A., & Swartz, M. A. (2007). Engineered blood and lymphatic capillaries in 3-D VEGF-fibrin-collagen matrices with interstitial flow. Biotechnology and Bioengineering, 96, 167–176.CrossRefGoogle Scholar
  18. 18.
    Hernández Vera, R., Genové, E., Alvarez, L., Borrós, S., Kamm, R., Lauffenburger, D., et al. (2009). Interstitial fluid flow intensity modulates endothelial sprouting in restricted Src-activated cell clusters during capillary morphogenesis. Tissue Engineering. Part A, 15, 175–185.CrossRefGoogle Scholar
  19. 19.
    Huang, A. H., Balestrini, J. L., Udelsman, B. V., Zhou, K. C., Zhao, L., Ferruzzi, J., et al. (2016). Biaxial stretch improves elastic fiber maturation, collagen arrangement, and mechanical properties in engineered arteries. Tissue Engineering. Part C, Methods, 22, 524–533.CrossRefGoogle Scholar
  20. 20.
    Ingber, D. E. (2002). Mechanical signaling and the cellular response to extracellular matrix in angiogenesis and cardiovascular physiology. Circulation Research, 91, 877–887.CrossRefGoogle Scholar
  21. 21.
    Jeon, J. S., Bersini, S., Whisler, J. A., Chen, M. B., Dubini, G., Charest, J. L., et al. (2014). Generation of 3D functional microvascular networks with human mesenchymal stem cells in microfluidic systems. Integrative Biology, 6, 555–563.CrossRefGoogle Scholar
  22. 22.
    Kaunas, R., & Deguchi, S. (2016). Cyclic stretch-induced reorganization of stress fibers in endothelial cells. Vascular engineering (pp. 99–110). Tokyo: Springer.Google Scholar
  23. 23.
    Kim, S., Lee, H., Chung, M., & Jeon, N. L. (2013). Engineering of functional, perfusable 3D microvascular networks on a chip. Lab on a Chip, 13, 1489–1500.CrossRefGoogle Scholar
  24. 24.
    Kniazeva, E., & Putnam, A. J. (2009). Endothelial cell traction and ECM density influence both capillary morphogenesis and maintenance in 3-D. American Journal of Physiology. Cell Physiology, 297, C179–C187.CrossRefGoogle Scholar
  25. 25.
    Kniazeva, E., Weidling, J. W., Singh, R., Botvinick, E. L., Digman, M. A., Gratton, E., et al. (2012). Quantification of local matrix deformations and mechanical properties during capillary morphogenesis in 3D. Integrative Biology, 4, 431–439.CrossRefGoogle Scholar
  26. 26.
    Korff, T., & Augustin, H. G. (1999). Tensional forces in fibrillar extracellular matrices control directional capillary sprouting. Journal of Cell Science, 112(Pt 19), 3249–3258.Google Scholar
  27. 27.
    Krishnan, L., Underwood, C. J., Maas, S., Ellis, B. J., Kode, T. C., Hoying, J. B., et al. (2008). Effect of mechanical boundary conditions on orientation of angiogenic microvessels. Cardiovascular Research, 78, 324–332.CrossRefGoogle Scholar
  28. 28.
    Krishnan, R., Klumpers, D. D., Park, C. Y., Rajendran, K., Trepat, X., van Bezu, J., et al. (2011). Substrate stiffening promotes endothelial monolayer disruption through enhanced physical forces. American Journal of Physiology. Cell Physiology, 300, C146–C154.CrossRefGoogle Scholar
  29. 29.
    Lee, E. J., & Niklason, L. E. (2010). A novel flow bioreactor for in vitro microvascularization. Tissue Engineering. Part C, Methods, 16, 1191–1200.CrossRefGoogle Scholar
  30. 30.
    Lee, P.-F., Yeh, A. T., & Bayless, K. J. (2009). Nonlinear optical microscopy reveals invading endothelial cells anisotropically alter three-dimensional collagen matrices. Experimental Cell Research, 315, 396–410.ADSCrossRefGoogle Scholar
  31. 31.
    Lesman, A., Koffler, J., Atlas, R., Blinder, Y. J., Kam, Z., & Levenberg, S. (2011). Engineering vessel-like networks within multicellular fibrin-based constructs. Biomaterials, 32, 7856–7869.CrossRefGoogle Scholar
  32. 32.
    Lesman, A., Notbohm, J., Tirrell, D. A., & Ravichandran, G. (2014). Contractile forces regulate cell division in three-dimensional environments. The Journal of Cell Biology, 205, 155–162.CrossRefGoogle Scholar
  33. 33.
    Li, Y.-S. J., Haga, J. H., & Chien, S. (2005). Molecular basis of the effects of shear stress on vascular endothelial cells. Journal of Biomechanics, 38, 1949–1971.CrossRefGoogle Scholar
  34. 34.
    Liu, S. Q. (1998). Influence of tensile strain on smooth muscle cell orientation in rat blood vessels. Journal of Biomechanical Engineering, 120, 313–320.CrossRefGoogle Scholar
  35. 35.
    Lu, D., & Kassab, G. S. (2011). Role of shear stress and stretch in vascular mechanobiology. Journal of the Royal Society Interface, 8, 1379–1385.CrossRefGoogle Scholar
  36. 36.
    Mason, B. N., Starchenko, A., Williams, R. M., Bonassar, L. J., & Reinhart-King, C. A. (2013). Tuning three-dimensional collagen matrix stiffness independently of collagen concentration modulates endothelial cell behavior. Acta Biomaterialia, 9, 4635–4644.CrossRefGoogle Scholar
  37. 37.
    Matsumoto, T., Yung, Y. C., Fischbach, C., Kong, H. J., Nakaoka, R., & Mooney, D. J. (2007). Mechanical strain regulates endothelial cell patterning in vitro. Tissue Engineering, 13, 207–217.CrossRefGoogle Scholar
  38. 38.
    Munevar, S., Wang, Y., & Dembo, M. (2001). Traction force microscopy of migrating normal and H-ras transformed 3T3 fibroblasts. Biophysical Journal, 80, 1744–1757.ADSCrossRefGoogle Scholar
  39. 39.
    Ng, C. P., Helm, C.-L. E., & Swartz, M. A. (2004). Interstitial flow differentially stimulates blood and lymphatic endothelial cell morphogenesis in vitro. Microvascular Research, 68, 258–264.CrossRefGoogle Scholar
  40. 40.
    Nicoli, S., Standley, C., Walker, P., Hurlstone, A., Fogarty, K. E., & Lawson, N. D. (2010). MicroRNA-mediated integration of haemodynamics and Vegf signalling during angiogenesis. Nature, 464, 1196–1200.ADSCrossRefGoogle Scholar
  41. 41.
    Pelham Jr., R. J., & Yl, W. (1997). Cell locomotion and focal adhesions are regulated by substrate flexibility. Proceedings of the National Academy of Sciences of the United States of America, 94, 13661–13665.ADSCrossRefGoogle Scholar
  42. 42.
    Reinhart-King, C. A., Dembo, M., & Hammer, D. A. (2003). Endothelial cell traction forces on RGD-derivatized polyacrylamide substrata. Langmuir, 19, 1573–1579.CrossRefGoogle Scholar
  43. 43.
    Reinhart-King, C. A., Dembo, M., & Hammer, D. A. (2008). Cell-cell mechanical communication through compliant substrates. Biophysical Journal, 95, 6044–6051.ADSCrossRefGoogle Scholar
  44. 44.
    Resnick, N., Yahav, H., Shay-Salit, A., Shushy, M., Schubert, S., Zilberman, L. C. M., et al. (2003). Fluid shear stress and the vascular endothelium: For better and for worse. Progress in Biophysics and Molecular Biology, 81, 177–199.CrossRefGoogle Scholar
  45. 45.
    Rosenfeld, D., Landau, S., Shandalov, Y., Raindel, N., Freiman, A., Shor, E., et al. (2016). Morphogenesis of 3D vascular networks is regulated by tensile forces. Proceedings of the National Academy of Sciences of the United States of America, 113, 3215–3220.ADSCrossRefGoogle Scholar
  46. 46.
    Rotenberg, M. Y., Ruvinov, E., Armoza, A., & Cohen, S. (2012). A multi-shear perfusion bioreactor for investigating shear stress effects in endothelial cell constructs. Lab on a Chip, 12, 2696–2703.CrossRefGoogle Scholar
  47. 47.
    Santos, L., Fuhrmann, G., Juenet, M., Amdursky, N., Horejs, C.-M., Campagnolo, P., et al. (2015). Extracellular stiffness modulates the expression of functional proteins and growth factors in endothelial cells. Advanced Healthcare Materials, 4(14), 2056–2063.CrossRefGoogle Scholar
  48. 48.
    Shamloo, A., & Heilshorn, S. C. (2010). Matrix density mediates polarization and lumen formation of endothelial sprouts in VEGF gradients. Lab on a Chip, 10, 3061–3068.CrossRefGoogle Scholar
  49. 49.
    Steward Jr., R., Tambe, D., Hardin, C. C., Krishnan, R., & Fredberg, J. J. (2015). Fluid shear, intercellular stress, and endothelial cell alignment. American Journal of Physiology. Cell Physiology, 308, C657–C664.CrossRefGoogle Scholar
  50. 50.
    Sun, J., Jamilpour, N., Wang, F.-Y., & Wong, P. K. (2014). Geometric control of capillary architecture via cell-matrix mechanical interactions. Biomaterials, 35, 3273–3280.CrossRefGoogle Scholar
  51. 51.
    Ueda, A., Koga, M., Ikeda, M., Kudo, S., & Tanishita, K. (2004). Effect of shear stress on microvessel network formation of endothelial cells with in vitro three-dimensional model. American Journal of Physiology. Heart and Circulatory Physiology, 287, H994–H1002.CrossRefGoogle Scholar
  52. 52.
    Underwood, C. J., Edgar, L. T., Hoying, J. B., & Weiss, J. A. (2014). Cell-generated traction forces and the resulting matrix deformation modulate microvascular alignment and growth during angiogenesis. American Journal of Physiology. Heart and Circulatory Physiology, 307, H152–H164.CrossRefGoogle Scholar
  53. 53.
    Vailhé, B., Ronot, X., Tracqui, P., Usson, Y., & Tranqui, L. (1997). In vitro angiogenesis is modulated by the mechanical properties of fibrin gels and is related to αvβ3 integrin localization. In Vitro Cellular & Developmental Biology – Animal, 33, 763–773.CrossRefGoogle Scholar
  54. 54.
    van der Schaft, D. W. J., van Spreeuwel, A. C. C., van Assen, H. C., & Baaijens, F. P. T. (2011). Mechanoregulation of vascularization in aligned tissue-engineered muscle: A role for vascular endothelial growth factor. Tissue Engineering. Part A, 17, 2857–2865.CrossRefGoogle Scholar
  55. 55.
    Vickerman, V., & Kamm, R. D. (2012). Mechanism of a flow-gated angiogenesis switch: Early signaling events at cell--matrix and cell--cell junctions. Integrative Biology, 4, 863–874.CrossRefGoogle Scholar
  56. 56.
    Walshe, T. E., dela Paz, N. G., & D’Amore, P. A. (2013). The role of shear-induced transforming growth factor-signaling in the endothelium. Arteriosclerosis, Thrombosis, and Vascular Biology, 33, 2608–2617.CrossRefGoogle Scholar
  57. 57.
    Wang, X., Phan, D. T. T., Sobrino, A., George, S. C., Hughes, C. C. W., & Lee, A. P. (2016). Engineering anastomosis between living capillary networks and endothelial cell-lined microfluidic channels. Lab on a Chip, 16, 282–290.CrossRefGoogle Scholar
  58. 58.
    Wanjare, M., Agarwal, N., & Gerecht, S. (2015). Biomechanical strain induces elastin and collagen production in human pluripotent stem cell-derived vascular smooth muscle cells. American Journal of Physiology. Cell Physiology, 309, C271–C281.CrossRefGoogle Scholar
  59. 59.
    Wilkins, J. R., Pike, D. B., Gibson, C. C., Li, L., & Shiu, Y.-T. (2015). The interplay of cyclic stretch and vascular endothelial growth factor in regulating the initial steps for angiogenesis. Biotechnology Progress, 31, 248–257.CrossRefGoogle Scholar
  60. 60.
    Yamamura, N., Sudo, R., Ikeda, M., & Tanishita, K. (2007). Effects of the mechanical properties of collagen gel on the in vitro formation of microvessel networks by endothelial cells. Tissue Engineering, 13, 1443–1453.CrossRefGoogle Scholar
  61. 61.
    Yeung, T., Georges, P. C., Flanagan, L. A., Marg, B., Ortiz, M., Funaki, M., et al. (2005). Effects of substrate stiffness on cell morphology, cytoskeletal structure, and adhesion. Cell Motility and the Cytoskeleton, 60, 24–34.CrossRefGoogle Scholar
  62. 62.
    Yung, Y. C., Chae, J., Buehler, M. J., Hunter, C. P., & Mooney, D. J. (2009). Cyclic tensile strain triggers a sequence of autocrine and paracrine signaling to regulate angiogenic sprouting in human vascular cells. Proceedings of the National Academy of Sciences of the United States of America, 106, 15279–15284.ADSCrossRefGoogle Scholar
  63. 63.
    Zohar, B., Blinder, Y., Mooney, D. J., & Levenberg, S. (2018). Flow-induced vascular network formation and maturation in three-dimensional engineered tissue. ACS Biomaterials Science & Engineering, 4(4), 1265–1271.CrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2018

Authors and Affiliations

  1. 1.Department of Biomedical EngineeringTechnion-Israel Institute of TechnologyHaifaIsrael

Personalised recommendations