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Hypoxia and Matrix Manipulation for Vascular Engineering

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Biophysical Regulation of Vascular Differentiation and Assembly

Abstract

The substantial majority of cell types are known to be capable of sensing changes in O2 tension and in the extracellular matrix (ECM), resulting in various responses depending on the cell type and other factors in the microenvironment, such as cell-cell interactions. A growing body of evidence suggests that hypoxia greatly influences angiogenesis and vasculogenesis through the transcription of numerous genes, including vascular endothelial growth factor (VEGF), the major regulatory protein of these processes. At the same time, the spatial and temporal distribution of ECM components affects ECM properties and growth factor (GF) availability, which, in turn, regulates vascular development. This chapter will discuss how hypoxia and the ECM influence vascular morphogenesis. It seeks to provide a better understanding of vascular development by considering recent research and emerging technologies focused on controlling O2 tension and manipulating ECM properties. We will first focus on the influences of O2 tension and ECM composition on neovascularization. Then we present strategies for manipulating the microenvironment using both synthetic and naturally derived biomaterials. Control over O2 in three-dimensional (3D) microenvironments is thoroughly highlighted, along with the currently available O2 measurement techniques and mathematical models that are necessary to monitor O2 gradients in 3D microenvironments. Finally, we discuss the state-of-the-art technology in microfluidics and smart biomaterials to provide insight into future directions of these exciting research areas.

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References

  1. Abaci, H. E., Truitt, R., Luong, E., Drazer, G., & Gerecht, S. (2010). Adaptation to oxygen deprivation in cultures of human pluripotent stem cells, endothelial progenitor cells, and umbilical vein endothelial cells. American Journal of Physiology. Cell Physiology, 298(6), C1527–C1537.

    Article  Google Scholar 

  2. Abaci, H. E., Devendra, R., Smith, Q., Gerecht, S., & Drazer, G. (2012). Design and development of microbioreactors for long-term cell culture in controlled oxygen microenvironments. Biomedical Microdevices, 14(1), 145–152.

    Article  Google Scholar 

  3. Abaci, H. E., Shen, Y. I., Tan, S., & Gerecht, S. (2014). Recapitulating physiological and pathological shear stress and oxygen to model vasculature in health and disease. Scientific Reports, 4, 9.

    Google Scholar 

  4. Abbott, J. D., Huang, Y., Liu, D., Hickey, R., Krause, D. S., & Giordano, F. J. (2004). Stromal cell-derived factor-1 alpha plays a critical role in stem cell recruitment to the heart after myocardial infarction but is not sufficient to induce homing in the absence of injury. Circulation, 110(21), 3300–3305.

    Article  Google Scholar 

  5. Adelman, D. M., Maltepe, E., & Simon, M. C. (1999). Multilineage embryonic hematopoiesis requires hypoxic ARNT activity. Genes & Development, 13(19), 2478–2483.

    Article  Google Scholar 

  6. Adler, M., Polinkovsky, M., Gutierrez, E., & Groisman, A. (2010). Generation of oxygen gradients with arbitrary shapes in a microfluidic device. Lab on a Chip, 10(3), 388–391.

    Article  Google Scholar 

  7. Airley, R., Loncaster, J., Davidson, S., Bromley, M., Roberts, S., Patterson, A., et al. (2001). Glucose transporter glut-1 expression correlates with tumor hypoxia and predicts metastasis-free survival in advanced carcinoma of the cervix. Clinical Cancer Research, 7(4), 928–934.

    Google Scholar 

  8. Akita, T., Murohara, T., Ikeda, H., Sasaki, K., Shimada, T., Egami, K., et al. (2003). Hypoxic preconditioning augments efficacy of human endothelial progenitor cells for therapeutic neovascularization. Laboratory Investigation, 83(1), 65–73.

    Article  Google Scholar 

  9. Albina, J. E., Mastrofrancesco, B., Vessella, J. A., Louis, C. A., Henry Jr., W. L., & Reichner, J. S. (2001). HIF-1 expression in healing wounds: HIF-1alpha induction in primary inflammatory cells by TNF-alpha. American Journal of Physiology. Cell Physiology, 281(6), C1971–C1977.

    Article  Google Scholar 

  10. Almany, L., & Seliktar, D. (2005). Biosynthetic hydrogel scaffolds made from fibrinogen and polyethylene glycol for 3D cell cultures. Biomaterials, 26(15), 2467–2477.

    Article  Google Scholar 

  11. Artuc, M., Hermes, B., Steckelings, U. M., Grutzkau, A., & Henz, B. M. (1999). Mast cells and their mediators in cutaneous wound healing--active participants or innocent bystanders? Experimental Dermatology, 8(1), 1–16.

    Article  Google Scholar 

  12. Asahara, T., & Kawamoto, A. (2004). Endothelial progenitor cells for postnatal vasculogenesis. American Journal of Physiology. Cell Physiology, 287(3), C572–C579.

    Article  Google Scholar 

  13. Asahara, T., Masuda, H., Takahashi, T., Kalka, C., Pastore, C., Silver, M., et al. (1999). Bone marrow origin of endothelial progenitor cells responsible for postnatal vasculogenesis in physiological and pathological neovascularization. Circulation Research, 85(3), 221–228.

    Article  Google Scholar 

  14. Astrof, S., Crowley, D., & Hynes, R. O. (2007). Multiple cardiovascular defects caused by the absence of alternatively spliced segments of fibronectin. Developmental Biology, 311(1), 11–24.

    Article  Google Scholar 

  15. Au, P., Tam, J., Fukumura, D., & Jain, R. K. (2008). Bone marrow derived mesenchymal stem cells facilitate engineering of long-lasting functional vasculature. Blood, 111(9), 4551–4558.

    Article  Google Scholar 

  16. Au, P., Daheron, L. M., Duda, D. G., Cohen, K. S., Tyrrell, J. A., Lanning, R. M., et al. (2008). Differential in vivo potential of endothelial progenitor cells from human umbilical cord blood and adult peripheral blood to form functional long-lasting vessels. Blood, 111(3), 1302–1305.

    Article  Google Scholar 

  17. Band, M., Joel, A., Hernandez, A., & Avivi, A. (2009). Hypoxia-induced BNIP3 expression and mitophagy: In vivo comparison of the rat and the hypoxia-tolerant mole rat, spalax ehrenbergi. FASEB Journal, 23(7), 2327–2335.

    Article  Google Scholar 

  18. Banerjee, S. D., & Toole, B. P. (1992). Hyaluronan-binding protein in endothelial cell morphogenesis. Journal of Cell Biology, 119(3), 643–652.

    Article  Google Scholar 

  19. Bekker, A., Holland, H. D., Wang, P. L., Rumble 3rd, D., Stein, H. J., Hannah, J. L., et al. (2004). Dating the rise of atmospheric oxygen. Nature, 427(6970), 117–120.

    Article  ADS  Google Scholar 

  20. Bellot, G., Garcia-Medina, R., Gounon, P., Chiche, J., Roux, D., Pouyssegur, J., et al. (2009). Hypoxia-induced autophagy is mediated through hypoxia-inducible factor induction of BNIP3 and BNIP3L via their BH3 domains. Molecular and Cellular Biology, 29(10), 2570–2581.

    Article  Google Scholar 

  21. Ben-Yosef, Y., Miller, A., Shapiro, S., & Lahat, N. (2005). Hypoxia of endothelial cells leads to MMP-2-dependent survival and death. American Journal of Physiology. Cell Physiology, 289(5), C1321–C1331.

    Article  Google Scholar 

  22. Berg, J. T., Breen, E. C., Fu, Z., Mathieu-Costello, O., & West, J. B. (1998). Alveolar hypoxia increases gene expression of extracellular matrix proteins and platelet-derived growth factor-B in lung parenchyma. American Journal of Respiratory and Critical Care Medicine, 158(6), 1920–1928.

    Article  Google Scholar 

  23. Bettinger, C. J., Zhang, Z., Gerecht, S., Borenstein, J., & Langer, R. (2008). Enhancement of in vitro capillary tube formation by substrate nanotopography. Advanced Materials, 20, 99–103.

    Article  Google Scholar 

  24. Bianchi, F., Rosi, M., Vozzi, G., Emanueli, C., Madeddu, P., & Ahluwalia, A. (2007). Microfabrication of fractal polymeric structures for capillary morphogenesis: Applications in therapeutic angiogenesis and in the engineering of vascularized tissue. Journal of Biomedical Materials Research. Part B, Applied Biomaterials, 81(2), 462–468.

    Article  Google Scholar 

  25. Blatchley, M., Park, K. M., & Gerecht, S. (2015). Designer hydrogels for precision control of oxygen tension and mechanical properties. Journal of Materials Chemistry B, 3(40), 7939–7949.

    Article  Google Scholar 

  26. Boveris, A., Costa, L. E., Poderoso, J. J., Carreras, M. C., & Cadenas, E. (2000). Regulation of mitochondrial respiration by oxygen and nitric oxide. Annals of the New York Academy of Sciences, 899, 121–135.

    Article  ADS  Google Scholar 

  27. Brown, D. A., MacLellan, W. R., Laks, H., Dunn, J. C., Wu, B. M., & Beygui, R. E. (2007). Analysis of oxygen transport in a diffusion-limited model of engineered heart tissue. Biotechnology and Bioengineering, 97(4), 962–975.

    Article  Google Scholar 

  28. Bruick, R. K., & McKnight, S. L. (2001). A conserved family of prolyl-4-hydroxylases that modify HIF. Science, 294(5545), 1337–1340.

    Article  ADS  Google Scholar 

  29. Burggren, W. W. (2004). What is the purpose of the embryonic heart beat? Or how facts can ultimately prevail over physiological dogma. Physiological and Biochemical Zoology, 77(3), 333–345.

    Article  Google Scholar 

  30. Camenisch, T. D., Spicer, A. P., Brehm-Gibson, T., Biesterfeldt, J., Augustine, M. L., Calabro Jr., A., et al. (2000). Disruption of hyaluronan synthase-2 abrogates normal cardiac morphogenesis and hyaluronan-mediated transformation of epithelium to mesenchyme. Journal of Clinical Investigation, 106(3), 349–360.

    Article  Google Scholar 

  31. Caspi, O., Lesman, A., Basevitch, Y., Gepstein, A., Arbel, G., Habib, I. H., et al. (2007). Tissue engineering of vascularized cardiac muscle from human embryonic stem cells. Circulation Research, 100, 263.

    Article  Google Scholar 

  32. Ceradini, D. J., & Gurtner, G. C. (2005). Homing to hypoxia: HIF-1 as a mediator of progenitor cell recruitment to injured tissue. Trends in Cardiovascular Medicine, 15(2), 57–63.

    Article  Google Scholar 

  33. Ceradini, D. J., Kulkarni, A. R., Callaghan, M. J., Tepper, O. M., Bastidas, N., Kleinman, M. E., et al. (2004). Progenitor cell trafficking is regulated by hypoxic gradients through HIF-1 induction of SDF-1. Nature Medicine, 10(8), 858–864.

    Article  Google Scholar 

  34. Chaudhuri, O., Gu, L., Klumpers, D., Darnell, M., Bencherif, S. A., Weaver, J. C., et al. (2016). Hydrogels with tunable stress relaxation regulate stem cell fate and activity. Nature Materials, 15(3), 326.

    Article  ADS  Google Scholar 

  35. Chavakis, E., Aicher, A., Heeschen, C., Sasaki, K. I., Kaiser, R., El Makhfi, N., et al. (2005). Role of beta 2-integrins for homing and neovascularization capacity of endothelial progenitor cells. Journal of Experimental Medicine, 201(1), 63–72.

    Article  Google Scholar 

  36. Cheema, U., Brown, R. A., Alp, B., & MacRobert, A. J. (2008). Spatially defined oxygen gradients and vascular endothelial growth factor expression in an engineered 3D cell model. Cellular and Molecular Life Sciences, 65(1), 177–186.

    Article  Google Scholar 

  37. Chen, Y. A., King, A. D., Shih, H. C., Peng, C. C., Wu, C. Y., Liao, W. H., et al. (2011). Generation of oxygen gradients in microfluidic devices for cell culture using spatially confined chemical reactions. Lab on a Chip, 11(21), 3626–3633.

    Article  Google Scholar 

  38. Cheresh, D. A., & Stupack, D. G. (2008). Regulation of angiogenesis: Apoptotic cues from the ECM. Oncogene, 27(48), 6285–6298.

    Article  Google Scholar 

  39. Chin, K., Khattak, S. F., Bhatia, S. R., & Roberts, S. C. (2008). Hydrogel-perfluorocarbon composite scaffold promotes oxygen transport to immobilized cells. Biotechnology Progress, 24(2), 358–366.

    Article  Google Scholar 

  40. Chiu, L. L. Y., & Radisic, M. (2010). Scaffolds with covalently immobilized VEGF and angiopoietin-1 for vascularization of engineered tissues. Biomaterials, 31(2), 226–241.

    Article  Google Scholar 

  41. Chow, D. C., Wenning, L. A., Miller, W. M., & Papoutsakis, E. T. (2001). Modeling pO(2) distributions in the bone marrow hematopoietic compartment. I. Krogh’s model. Biophysical Journal, 81(2), 675–684.

    Article  ADS  Google Scholar 

  42. Chung, S., & Andrew, D. J. (2008). The formation of epithelial tubes. Journal of Cell Science, 121(21), 3501–3504.

    Article  Google Scholar 

  43. Colville-Nash, P. R., & Scott, D. L. (1992). Angiogenesis and rheumatoid arthritis: Pathogenic and therapeutic implications. Annals of the Rheumatic Diseases, 51(7), 919–925.

    Article  Google Scholar 

  44. Cook, C. A., Hahn, K. C., Morrissette-McAlmon, J. B. F., & Grayson, W. L. (2015). Oxygen delivery from hyperbarically loaded microtanks extends cell viability in anoxic environments. Biomaterials, 52, 376–384.

    Article  Google Scholar 

  45. Covello, K. L., Kehler, J., Yu, H., Gordan, J. D., Arsham, A. M., Hu, C. J., et al. (2006). HIF-2alpha regulates Oct-4: Effects of hypoxia on stem cell function, embryonic development, and tumor growth. Genes & Development, 20(5), 557–570.

    Article  Google Scholar 

  46. Critser, P. J., Kreger, S. T., Voytik-Harbin, S. L., & Yoder, M. C. (2010). Collagen matrix physical properties modulate endothelial colony forming cell-derived vessels in vivo. Microvascular Research, 80, 23–30.

    Article  Google Scholar 

  47. Daphne, M. (2003). A mechanochemical model of angiogenesis and vasculogenesis. Modelisation mathematique et analyse numerique, 37(4), 581–599.

    MathSciNet  MATH  Google Scholar 

  48. Davis, G. E., & Camarillo, C. W. (1995). Regulation of endothelial cell morphogenesis by integrins, mechanical forces, and matrix guidance pathways. Experimental Cell Research, 216(1), 113–123.

    Article  Google Scholar 

  49. Davis, G. E., Koh, W., & Stratman, A. N. (2007). Mechanisms controlling human endothelial lumen formation and tube assembly in three-dimensional extracellular matrices. Birth Defects Research. Part C, Embryo Today, 81(4), 270–285.

    Article  Google Scholar 

  50. Davis, G. E., & Senger, D. R. (2008). Extracellular matrix mediates a molecular balance between vascular morphogenesis and regression. Current Opinion in Hematology, 15(3), 197–203.

    Article  Google Scholar 

  51. De Falco, E., Porcelli, D., Torella, A. R., Straino, S., Iachininoto, M. G., Orlandi, A., et al. (2004). SDF-1 involvement in endothelial phenotype and ischemia-induced recruitment of bone marrow progenitor cells. Blood, 104(12), 3472–3482.

    Article  Google Scholar 

  52. Deroanne, C. F., Lapiere, C. M., & Nusgens, B. V. (2001). In vitro tubulogenesis of endothelial cells by relaxation of the coupling extracellular matrix-cytoskeleton. Cardiovascular Research, 49(3), 647–658.

    Article  Google Scholar 

  53. Desgrosellier, J. S., & Cheresh, D. A. (2010). Integrins in cancer: Biological implications and therapeutic opportunities. Nature Reviews Cancer, 10(1), 9–22.

    Article  Google Scholar 

  54. Dickinson, L. E., Moura, M. E., & Gerecht, S. (2010). Guiding endothelial progenitor cell tube formation using patterned fibronectin surfaces. Soft Matter, 6(20), 5109–5119.

    Article  ADS  Google Scholar 

  55. Dickinson, L. E., Ho, C. C., Wang, G. M., Stebe, K. J., & Gerecht, S. (2010). Functional surfaces for high-resolution analysis of cancer cell interactions on exogenous hyaluronic acid. Biomaterials, 31(20), 5472–5478.

    Article  Google Scholar 

  56. Drake, C. J., & Fleming, P. A. (2000). Vasculogenesis in the day 6.5 to 9.5 mouse embryo. Blood, 95(5), 1671–1679.

    Google Scholar 

  57. Eble, J. A., & Niland, S. (2009). The extracellular matrix of blood vessels. Current Pharmaceutical Design, 15, 1385–1400.

    Article  Google Scholar 

  58. Ehrbar, M., Djonov, V. G., Schnell, C., Tschanz, S. A., Martiny-Baron, G., Schenk, U., et al. (2004). Cell-demanded liberation of VEGF121 from fibrin implants induces local and controlled blood vessel growth. Circulation Research, 94(8), 1124–1132.

    Article  Google Scholar 

  59. Ehrbar, M., Metters, A., Zammaretti, P., Hubbell, J. A., & Zisch, A. H. (2005). Endothelial cell proliferation and progenitor maturation by fibrin-bound VEGF variants with differential susceptibilities to local cellular activity. Journal of Controlled Release, 101(1-3), 93–109.

    Article  Google Scholar 

  60. Engler, A. J., Sen, S., Sweeney, H. L., & Discher, D. E. (2006). Matrix elasticity directs stem cell lineage specification. Cell, 126(4), 677–689.

    Article  Google Scholar 

  61. Erler, J. T., Bennewith, K. L., Cox, T. R., Lang, G., Bird, D., Koong, A., et al. (2009). Hypoxia-induced lysyl oxidase is a critical mediator of bone marrow cell recruitment to form the premetastatic niche. Cancer Cell, 15(1), 35–44.

    Article  Google Scholar 

  62. Evanko, S. P., Parks, W. T., & Wight, T. N. (2004). Intracellular hyaluronan in arterial smooth muscle cells: Association with microtubules, RHAMM, and the mitotic spindle. The Journal of Histochemistry and Cytochemistry, 52(12), 1525–1535.

    Article  Google Scholar 

  63. Evans, A. M., Mustard, K. J., Wyatt, C. N., Peers, C., Dipp, M., Kumar, P., et al. (2005). Does AMP-activated protein kinase couple inhibition of mitochondrial oxidative phosphorylation by hypoxia to calcium signaling in O2-sensing cells? The Journal of Biological Chemistry, 280(50), 41504–41511.

    Article  Google Scholar 

  64. Ezashi, T., Das, P., & Roberts, R. M. (2005). Low O2 tensions and the prevention of differentiation of hES cells. Proceedings of the National Academy of Sciences of the United States of America, 102(13), 4783–4788.

    Article  ADS  Google Scholar 

  65. Fahling, M., Perlewitz, A., Doller, A., & Thiele, B. J. (2004). Regulation of collagen prolyl 4-hydroxylase and matrix metalloproteinases in fibrosarcoma cells by hypoxia. Comparative Biochemistry and Physiology, Part C: Toxicology & Pharmacology, 139(1-3), 119–126.

    Google Scholar 

  66. Figallo, E., Cannizzaro, C., Gerecht, S., Burdick, J. A., Langer, R., Elvassore, N., et al. (2007). Micro-bioreactor array for controlling cellular microenvironments. Lab on a Chip, 7(6), 710–719.

    Article  Google Scholar 

  67. Folkman, J., Haudenschild, C. C., & Zetter, B. R. (1979). Long-term culture of capillary endothelial cells. Proceedings of the National Academy of Sciences of the United States of America, 76(10), 5217–5221.

    Article  ADS  Google Scholar 

  68. Fong, G. H. (2009). Regulation of angiogenesis by oxygen sensing mechanisms. Journal of Molecular Medicine, 87(6), 549–560.

    Article  Google Scholar 

  69. Forristal, C. E., Wright, K. L., Hanley, N. A., Oreffo, R. O., & Houghton, F. D. (2010). Hypoxia inducible factors regulate pluripotency and proliferation in human embryonic stem cells cultured at reduced oxygen tensions. Reproduction, 139(1), 85–97.

    Article  Google Scholar 

  70. Fraisl, P., Mazzone, M., Schmidt, T., & Carmeliet, P. (2009). Regulation of angiogenesis by oxygen and metabolism. Developmental Cell, 16(2), 167–179.

    Article  Google Scholar 

  71. Francis, S. E., Goh, K. L., Hodivala-Dilke, K., Bader, B. L., Stark, M., Davidson, D., et al. (2002). Central roles of alpha5beta1 integrin and fibronectin in vascular development in mouse embryos and embryoid bodies. Arteriosclerosis, Thrombosis, and Vascular Biology, 22(6), 927–933.

    Article  Google Scholar 

  72. Frei, R., Gaucher, C., Poulton, S. W., & Canfield, D. E. (2009). Fluctuations in Precambrian atmospheric oxygenation recorded by chromium isotopes. Nature, 461(7261), 250–253.

    Article  ADS  Google Scholar 

  73. Fukumura, D., Kashiwagi, S., & Jain, R. K. (2006). The role of nitric oxide in tumour progression. Nature Reviews. Cancer, 6(7), 521–534.

    Article  Google Scholar 

  74. Funamoto, K., Zervantonakis, I. K., Liu, Y. C., Ochs, C. J., Kim, C., & Kamm, R. D. (2012). A novel microfluidic platform for high-resolution imaging of a three-dimensional cell culture under a controlled hypoxic environment. Lab on a Chip, 12(22), 4855–4863.

    Article  Google Scholar 

  75. Gafni, Y., Zilberman, Y., Ophir, Z., Abramovitch, R., Jaffe, M., Gazit, Z., et al. (2006). Design of a filamentous polymeric scaffold for in vivo guided angiogenesis. Tissue Engineering, 12(11), 3021–3034.

    Article  Google Scholar 

  76. Galban, C. J., & Locke, B. R. (1999). Effects of spatial variation of cells and nutrient and product concentrations coupled with product inhibition on cell growth in a polymer scaffold. Biotechnology and Bioengineering, 64(6), 633–643.

    Article  Google Scholar 

  77. Galban, C. J., & Locke, B. R. (1999). Analysis of cell growth kinetics and substrate diffusion in a polymer scaffold. Biotechnology and Bioengineering, 65(2), 121–132.

    Article  Google Scholar 

  78. Garedew, A., Kammerer, U., & Singer, D. (2009). Respiratory response of malignant and placental cells to changes in oxygen concentration. Respiratory Physiology & Neurobiology, 165(2-3), 154–160.

    Article  Google Scholar 

  79. Gerecht, S., Burdick, J. A., Ferreira, L. S., Townsend, S. A., Langer, R., & Vunjak-Novakovic, G. (2007). Hyaluronic acid hydrogel for controlled self-renewal and differentiation of human embryonic stem cells. Proceedings of the National Academy of Sciences of the United States of America, 104(27), 11298–11303.

    Article  ADS  Google Scholar 

  80. Gerecht-Nir, S., Cohen, S., Ziskind, A., & Itskovitz-Eldor, J. (2004). Three-dimensional porous alginate scaffolds provide a conducive environment for generation of well-vascularized embryoid bodies from human embryonic stem cells. Biotechnology and Bioengineering, 88(3), 313–320.

    Article  Google Scholar 

  81. Giannelli, G., Falk-Marzillier, J., Schiraldi, O., Stetler-Stevenson, W. G., & Quaranta, V. (1997). Induction of cell migration by matrix metalloprotease-2 cleavage of laminin-5. Science, 277(5323), 225–228.

    Article  Google Scholar 

  82. Gobin, A. S., & West, J. L. (2002). Cell migration through defined, synthetic extracellular matrix analogues. The FASEB Journal, 16, 751–753.

    Article  Google Scholar 

  83. Guaccio, A., Borselli, C., Oliviero, O., & Netti, P. A. (2008). Oxygen consumption of chondrocytes in agarose and collagen gels: A comparative analysis. Biomaterials, 29(10), 1484–1493.

    Article  Google Scholar 

  84. Hadden, W. J., Young, J. L., Holle, A. W., McFetridge, M. L., Kim, D. Y., Wijesinghe, P., et al. (2017). Stem cell migration and mechanotransduction on linear stiffness gradient hydrogels. Proceedings of the National Academy of Sciences of the United States of America, 114(22), 5647–5652.

    Article  Google Scholar 

  85. Hagemann, T., Robinson, S. C., Schulz, M., Trumper, L., Balkwill, F. R., & Binder, C. (2004). Enhanced invasiveness of breast cancer cell lines upon co-cultivation with macrophages is due to TNF-alpha dependent up-regulation of matrix metalloproteases. Carcinogenesis, 25(8), 1543–1549.

    Article  Google Scholar 

  86. Hanjaya-Putra, D., & Gerecht, S. (2009). Vascular engineering using human embryonic stem cells. Biotechnology Progress, 25(1), 2–9.

    Article  Google Scholar 

  87. Hanjaya-Putra, D., & Gerecht, S. (2009). Mending the failing heart with a vascularized cardiac patch. Cell Stem Cell, 5(6), 575–576.

    Article  Google Scholar 

  88. Hanjaya-Putra, D., Yee, J., Ceci, D., Truitt, R., Yee, D., & Gerecht, S. (2009). Vascular endothelial growth factor and substrate mechanics regulate in vitro tubulogenesis of endothelial progenitor cells. Journal of Cellular and Molecular Medicine, 14(10), 2436–2447.

    Article  Google Scholar 

  89. Hanjaya-Putra, D., Bose, V., Shen, Y. I., Yee, J., Khetan, S., Fox-Talbot, K., et al. (2011). Controlled activation of morphogenesis to generate a functional human microvasculature in a synthetic matrix. Blood, 118(3), 804–815.

    Article  Google Scholar 

  90. Hanjaya-Putra, D., Wong, K. T., Hirotsu, K., Khetan, S., Burdick, J. A., & Gerecht, S. (2012). Spatial control of cell-mediated degradation to regulate vasculogenesis and angiogenesis in hyaluronan hydrogels. Biomaterials, 33(26), 6123–6131.

    Article  Google Scholar 

  91. Harrison, J. S., Rameshwar, P., Chang, V., & Bandari, P. (2002). Oxygen saturation in the bone marrow of healthy volunteers. Blood, 99(1), 394.

    Article  Google Scholar 

  92. Heissig, B., Hattori, K., Dias, S., Friedrich, M., Ferris, B., Hackett, N. R., et al. (2002). Recruitment of stem and progenitor cells from the bone marrow niche requires MMP-9 mediated release of kit-ligand. Cell, 109(5), 625–637.

    Article  Google Scholar 

  93. Helmlinger, G., Endo, M., Ferrara, N., Hlatky, L., & Jain, R. K. (2000). Formation of endothelial cell networks. Nature, 405(6783), 139–141.

    Article  ADS  Google Scholar 

  94. Hirota, K., & Semenza, G. L. (2005). Regulation of hypoxia-inducible factor 1 by prolyl and asparaginyl hydroxylases. Biochemical and Biophysical Research Communications, 338(1), 610–616.

    Article  Google Scholar 

  95. Hirschi, K. K., & D’Amore, P. A. (1996). Pericytes in the microvasculature. Cardiovascular Research, 32(4), 687–698.

    Article  Google Scholar 

  96. Hirschi, K. K., Ingram, D. A., & Yoder, M. C. (2008). Assessing identity, phenotype, and fate of endothelial progenitor cells. Arteriosclerosis, Thrombosis, and Vascular Biology, 28(9), 1584–1595.

    Article  Google Scholar 

  97. Hirschi, K. K., Rohovsky, S. A., & D’Amore, P. A. (1998). PDGF, TGF-Î2, and heterotypic cell-cell interactions mediate endothelial cell-induced recruitment of 10T1/2 cells and their differentiation to a smooth muscle fate. Journal of Cell Biology, 141(3), 805–814.

    Article  Google Scholar 

  98. Hirsila, M., Koivunen, P., Gunzler, V., Kivirikko, K. I., & Myllyharju, J. (2003). Characterization of the human prolyl 4-hydroxylases that modify the hypoxia-inducible factor. The Journal of Biological Chemistry, 278(33), 30772–30780.

    Article  Google Scholar 

  99. Hofmann, U. B., Westphal, J. R., Van Kraats, A. A., Ruiter, D. J., & Van Muijen, G. N. (2000). Expression of integrin alpha(v)beta(3) correlates with activation of membrane-type matrix metalloproteinase-1 (MT1-MMP) and matrix metalloproteinase-2 (MMP-2) in human melanoma cells in vitro and in vivo. International Journal of Cancer, 87(1), 12–19.

    Article  Google Scholar 

  100. Holash, J., Wiegand, S. J., & Yancopoulos, G. D. (1999). New model of tumor angiogenesis: Dynamic balance between vessel regression and growth mediated by angiopoietins and VEGF. Oncogene, 18(38), 5356–5362.

    Article  Google Scholar 

  101. Holash, J., Maisonpierre, P. C., Compton, D., Boland, P., Alexander, C. R., Zagzag, D., et al. (1999). Vessel cooption, regression, and growth in tumors mediated by angiopoietins and VEGF. Science, 284(5422), 1994–1998.

    Article  Google Scholar 

  102. Hopf, H. W., & Rollins, M. D. (2007). Wounds: An overview of the role of oxygen. Antioxidants & Redox Signaling, 9(8), 1183–1192.

    Article  Google Scholar 

  103. Horino, Y., Takahashi, S., Miura, T., & Takahashi, Y. (2002). Prolonged hypoxia accelerates the posttranscriptional process of collagen synthesis in cultured fibroblasts. Life Sciences, 71(26), 3031–3045.

    Article  Google Scholar 

  104. Hou, L. Q., CoIler, J., Natu, V., Hastie, T. J., & Huang, N. F. (2016). Combinatorial extracellular matrix microenvironments promote survival and phenotype of human induced pluripotent stem cell-derived endothelial cells in hypoxia. Acta Biomaterialia, 44, 188–199.

    Article  Google Scholar 

  105. Hou, L. Q., Kim, J. J., Wanjare, M., Patlolla, B., Coller, J., Natu, V., et al. (2017). Combinatorial extracellular matrix microenvironments for probing endothelial differentiation of human pluripotent stem cells. Scientific Reports, 7, 12.

    Article  ADS  Google Scholar 

  106. Huang, P. H., Chen, Y. H., Wang, C. H., Chen, J. S., Tsai, H. Y., Lin, F. Y., et al. (2009). Matrix metalloproteinase-9 is essential for ischemia-induced neovascularization by modulating bone marrow-derived endothelial progenitor cells. Arteriosclerosis, Thrombosis, and Vascular Biology, 29(8), 1179–1U58.

    Article  Google Scholar 

  107. Huber, T. L., Kouskoff, V., Fehling, H. J., Palis, J., & Keller, G. (2004). Haemangioblast commitment is initiated in the primitive streak of the mouse embryo. Nature, 432(7017), 625–630.

    Article  ADS  Google Scholar 

  108. Igarashi, S., Tanaka, J., & Kobayashi, H. (2007). Micro-patterned nanofibrous biomaterials. Journal of Nanoscience and Nanotechnology, 7(3), 814–817.

    Article  Google Scholar 

  109. Ingber, D. E. (2002). Mechanical signaling and the cellular response to extracellular matrix in angiogenesis and cardiovascular physiology. Circulation Research, 91(10), 877–887.

    Article  Google Scholar 

  110. Ingber, D. E., & Folkman, J. (1989). Mechanochemical switching between growth and differentiation during fibroblast growth factor-stimulated angiogenesis in vitro: Role of extracellular matrix. Journal of Cell Biology, 109(1), 317–330.

    Article  Google Scholar 

  111. Iwasaki, H. (2009). The Niche regulation of hematopoietic stem cells. In Regulatory networks in stem cells (pp. 165–175). New York: Humana Press.

    Chapter  Google Scholar 

  112. Iyer, R. K., Radisic, M., Cannizzaro, C., & Vunjak-Novakovic, G. (2007). Synthetic oxygen carriers in cardiac tissue engineering. Artificial Cells, Blood Substitutes, and Immobilization Biotechnology, 35(1), 135–148.

    Article  Google Scholar 

  113. Jain, R. K. (2003). Molecular regulation of vessel maturation. Nature Medicine, 9(6), 685–693.

    Article  Google Scholar 

  114. Jain, R. K., Au, P., Tam, J., Duda, D. G., & Fukumura, D. (2005). Engineering vascularized tissue. Nature Biotechnology, 23(7), 821–823.

    Article  Google Scholar 

  115. Jauniaux, E., Gulbis, B., & Burton, G. J. (2003). The human first trimester gestational sac limits rather than facilitates oxygen transfer to the foetus--a review. Placenta, 24(Suppl A), S86–S93.

    Article  Google Scholar 

  116. Ji, L., Liu, Y. X., Yang, C., Yue, W., Shi, S. S., Bai, C. X., et al. (2009). Self-renewal and pluripotency is maintained in human embryonic stem cells by co-culture with human fetal liver stromal cells expressing hypoxia inducible factor 1alpha. Journal of Cellular Physiology, 221(1), 54–66.

    Article  Google Scholar 

  117. Jiang, M., Wang, B., Wang, C., He, B., Fan, H., Guo, T. B., et al. (2008). Angiogenesis by transplantation of HIF-1 alpha modified EPCs into ischemic limbs. Journal of Cellular Biochemistry, 103(1), 321–334.

    Article  Google Scholar 

  118. Jones 3rd, C. I., Han, Z., Presley, T., Varadharaj, S., Zweier, J. L., Ilangovan, G., et al. (2008). Endothelial cell respiration is affected by the oxygen tension during shear exposure: Role of mitochondrial peroxynitrite. American Journal of Physiology. Cell Physiology, 295(1), C180–C191.

    Article  Google Scholar 

  119. Kang, X. L., Wei, X. X., Wang, X. H., Jiang, L., Niu, C., Zhang, J. Y., et al. (2016). Nox2 contributes to the arterial endothelial specification of mouse induced pluripotent stem cells by upregulating notch signaling. Scientific Reports, 6, 13.

    Article  ADS  Google Scholar 

  120. Kellner, K., Liebsch, G., Klimant, I., Wolfbeis, O. S., Blunk, T., Schulz, M. B., et al. (2002). Determination of oxygen gradients in engineered tissue using a fluorescent sensor. Biotechnology and Bioengineering, 80(1), 73–83.

    Article  Google Scholar 

  121. Khetan, S., Chung, C., & Burdick, J. A. (2009). Tuning hydrogel properties for applications in tissue engineering. Conference Proceedings: Annual International Conference of the IEEE Engineering in Medicine and Biology Society, 1, 2094–2096.

    Google Scholar 

  122. Kilarski, W. W., Samolov, B., Petersson, L., Kvanta, A., & Gerwins, P. (2009). Biomechanical regulation of blood vessel growth during tissue vascularization. Nature Medicine, 15(6), 657–664.

    Article  Google Scholar 

  123. Kloxin, A. M., Kasko, A. M., Salinas, C. N., & Anseth, K. S. (2009). Photodegradable hydrogels for dynamic tuning of physical and chemical properties. Science, 324(5923), 59–63.

    Article  ADS  Google Scholar 

  124. Klumb, L. A., & Horbett, T. A. (1992). Design of insulin delivery devices based on glucose sensitive membranes. Journal of Controlled Release, 18(1), 59–80.

    Article  Google Scholar 

  125. Koay, E. J., & Athanasiou, K. A. (2008). Hypoxic chondrogenic differentiation of human embryonic stem cells enhances cartilage protein synthesis and biomechanical functionality. Osteoarthritis and Cartilage, 16(12), 1450–1456.

    Article  Google Scholar 

  126. Koh, M. Y., & Powis, G. (2012). Passing the baton: The HIF switch. Trends in Biochemical Sciences, 37(9), 364–372.

    Article  Google Scholar 

  127. Koh, W., Stratman, A. N., Sacharidou, A., & Davis, G. E. (2008). In vitro three dimensional collagen matrix models of endothelial lumen formation during vasculogenesis and angiogenesis. Methods in Enzymology, 443, 83–101.

    Article  Google Scholar 

  128. Koike, N., et al. (2004). Tissue engineering: Creation of long-lasting blood vessels. Nature, 428, 138.

    Article  ADS  Google Scholar 

  129. Korin, N., Bransky, A., Dinnar, U., & Levenberg, S. (2009). Periodic “flow-stop” perfusion microchannel bioreactors for mammalian and human embryonic stem cell long-term culture. Biomedical Microdevices, 11(1), 87–94.

    Article  Google Scholar 

  130. Kreger, S. T., & Voytik-Harbin, S. L. (2009). Hyaluronan concentration within a 3D collagen matrix modulates matrix viscoelasticity, but not fibroblast response. Matrix Biology, 28(6), 336–346.

    Article  Google Scholar 

  131. Kumar, R., Stepanek, F., & Mantalaris, A. (2003). A conceptual model for oxygen transport in the human marrow. Modelling and Control in Biomedical Systems 2003 (Including Biological Systems). pp. 365–370.

    Article  Google Scholar 

  132. Kumar, R., Stepanek, F., & Mantalaris, A. (2004). An oxygen transport model for human bone marrow microcirculation. Food and Bioproducts Processing, 82(C2), 105–116.

    Article  Google Scholar 

  133. Kumar, R., Panoskaltsis, N., Stepanek, F., & Mantalaris, A. (2008). Coupled oxygen-carbon dioxide transport model for the human bone marrow. Food and Bioproducts Processing, 86(C3), 211–219.

    Article  Google Scholar 

  134. Kusuma, S., Zhao, S., & Gerecht, S. (2012). The extracellular matrix is a novel attribute of endothelial progenitors and of hypoxic mature endothelial cells. FASEB Journal, 26(12), 4925–4936.

    Article  Google Scholar 

  135. Kusuma, S., Peijnenburg, E., Patel, P., & Gerecht, S. (2014). Low oxygen tension enhances endothelial fate of human pluripotent stem cells. Arteriosclerosis, Thrombosis, and Vascular Biology, 34(4), 913–920.

    Article  Google Scholar 

  136. Lai, E. S., Huang, N. F., Cooke, J. P., & Fuller, G. G. (2012). Aligned nanofibrillar collagen regulates endothelial organization and migration. Regenerative Medicine, 7(5), 649–661.

    Article  Google Scholar 

  137. Landman, K. A., & Cai, A. Q. (2007). Cell proliferation and oxygen diffusion in a vascularising scaffold. Bulletin of Mathematical Biology, 69(7), 2405–2428.

    Article  MathSciNet  MATH  Google Scholar 

  138. Langer, R., & Tirrell, D. A. (2004). Designing materials for biology and medicine. Nature, 428(6982), 487–492.

    Article  ADS  Google Scholar 

  139. Lanza, V. A., Ambrosi, D., & Preziosi, L. (2006). Exogenous control of vascular network formation in vitro: A mathematical model. Networks and Heterogeneous Media, 1(4), 621–638.

    Article  MathSciNet  MATH  Google Scholar 

  140. Lee, S. W., Jeong, H. K., Lee, J. Y., Yang, J., Lee, E. J., Kim, S. Y., et al. (2012). Hypoxic priming of mESCs accelerates vascular-lineage differentiation through HIF1-mediated inverse regulation of Oct4 and VEGF. EMBO Molecular Medicine, 4(9), 924–938.

    Article  Google Scholar 

  141. Lee, Y. M., Jeong, C. H., Koo, S. Y., Son, M. J., Song, H. S., Bae, S. K., et al. (2001). Determination of hypoxic region by hypoxia marker in developing mouse embryos in vivo: A possible signal for vessel development. Developmental Dynamics, 220(2), 175–186.

    Article  Google Scholar 

  142. Levenberg, S., Rouwkema, J., Macdonald, M., Garfein, E. S., Kohane, D. S., Darland, D. C., et al. (2005). Engineering vascularized skeletal muscle tissue. Nature Biotechnology, 23(7), 879–884.

    Article  Google Scholar 

  143. Lewis, D. M., Park, K. M., Tang, V., Xu, Y., Pak, K., Eisinger-Mathason, T. S. K., et al. (2016). Intratumoral oxygen gradients mediate sarcoma cell invasion. Proceedings of the National Academy of Sciences, 113, 9292–9297.

    Article  ADS  Google Scholar 

  144. Lewis, D. M., Blatchley, M. R., Park, K. M., & Gerecht, S. (2017). O-2-controllable hydrogels for studying cellular responses to hypoxic gradients in three dimensions in vitro and in vivo. Nature Protocols, 12(8), 1620–1638.

    Article  Google Scholar 

  145. Lewis, M. C., Macarthur, B. D., Malda, J., Pettet, G., & Please, C. P. (2005). Heterogeneous proliferation within engineered cartilaginous tissue: The role of oxygen tension. Biotechnology and Bioengineering, 91(5), 607–615.

    Article  Google Scholar 

  146. Li, C., Issa, R., Kumar, P., Hampson, I. N., Lopez-Novoa, J. M., Bernabeu, C., et al. (2003). CD105 prevents apoptosis in hypoxic endothelial cells. Journal of Cell Science, 116(Pt 13), 2677–2685.

    Article  Google Scholar 

  147. Li, S. R., Nih, L. R., Bachman, H., Fei, P., Li, Y. L., Nam, E., et al. (2017). Hydrogels with precisely controlled integrin activation dictate vascular patterning and permeability. Nature Materials, 16(9), 953.

    Article  ADS  Google Scholar 

  148. Limper, A. H., & Roman, J. (1992). Fibronectin. A versatile matrix protein with roles in thoracic development, repair and infection. Chest, 101(6), 1663–1673.

    Article  Google Scholar 

  149. Lubarsky, B., & Krasnow, M. A. (2003). Tube morphogenesis: Making and shaping biological tubes. Cell, 112(1), 19–28.

    Article  Google Scholar 

  150. Lucitti, J. L., Jones, E. A., Huang, C., Chen, J., Fraser, S. E., & Dickinson, M. E. (2007). Vascular remodeling of the mouse yolk sac requires hemodynamic force. Development, 134(18), 3317–3326.

    Article  Google Scholar 

  151. Lutolf, M. P. (2009). Biomaterials: Spotlight on hydrogels. Nature Materials, 8(6), 451–453.

    Article  ADS  Google Scholar 

  152. Lutolf, M. P., & Hubbell, J. A. (2005). Synthetic biomaterials as instructive extracellular microenvironments for morphogenesis in tissue engineering. Nature Biotechnology, 23(1), 47–55.

    Article  Google Scholar 

  153. Lutolf, M. P., Lauer-Fields, J. L., Schmoekel, H. G., Metters, A. T., Weber, F. E., Fields, G. B., et al. (2003). Synthetic matrix metalloproteinase-sensitive hydrogels for the conduction of tissue regeneration: Engineering cell-invasion characteristics. Proceedings of the National Academy of Sciences of the United States of America, 100(9), 5413–5418.

    Article  ADS  Google Scholar 

  154. Lyons, T. W., Reinhard, C. T., & Planavsky, N. J. (2014). The rise of oxygen in Earth’s early ocean and atmosphere. Nature, 506(7488), 307–315.

    Article  ADS  Google Scholar 

  155. Ma, T., Grayson, W. L., Frohlich, M., & Vunjak-Novakovic, G. (2009). Hypoxia and stem cell-based engineering of mesenchymal tissues. Biotechnology Progress, 25(1), 32–42.

    Article  Google Scholar 

  156. Maltepe, E., & Simon, M. C. (1998). Oxygen, genes, and development: An analysis of the role of hypoxic gene regulation during murine vascular development. Journal of Molecular Medicine, 76(6), 391–401.

    Article  Google Scholar 

  157. Mamchaoui, K., & Saumon, G. (2000). A method for measuring the oxygen consumption of intact cell monolayers. American Journal of Physiology. Lung Cellular and Molecular Physiology, 278(4), L858–L863.

    Article  Google Scholar 

  158. Mammoto, A., Connor, K. M., Mammoto, T., Yung, C. W., Huh, D., Aderman, C. M., et al. (2009). A mechanosensitive transcriptional mechanism that controls angiogenesis. Nature, 457(7233), 1103–1108.

    Article  ADS  Google Scholar 

  159. Manalo, D. J., Rowan, A., Lavoie, T., Natarajan, L., Kelly, B. D., Ye, S. Q., et al. (2005). Transcriptional regulation of vascular endothelial cell responses to hypoxia by HIF-1. Blood, 105(2), 659–669.

    Article  Google Scholar 

  160. Martorell, L., Gentile, M., Rius, J., Rodriguez, C., Crespo, J., Badimon, L., et al. (2009). The hypoxia-inducible factor 1/NOR-1 axis regulates the survival response of endothelial cells to hypoxia. Molecular and Cellular Biology, 29(21), 5828–5842.

    Article  Google Scholar 

  161. Massabuau, J. C. (2001). From low arterial- to low tissue-oxygenation strategy. An evolutionary theory. Respiration Physiology, 128(3), 249–261.

    Article  Google Scholar 

  162. Massabuau, J. C. (2003). Primitive, and protective, our cellular oxygenation status? Mechanisms of Ageing and Development, 124(8-9), 857–863.

    Article  Google Scholar 

  163. Mehta, G., Mehta, K., Sud, D., Song, J. W., Bersano-Begey, T., Futai, N., et al. (2007). Quantitative measurement and control of oxygen levels in microfluidic poly(dimethylsiloxane) bioreactors during cell culture. Biomedical Microdevices, 9(2), 123–134.

    Article  Google Scholar 

  164. Melero-Martin, J. M., De Obaldia, M. E., Kang, S. Y., Khan, Z. A., Yuan, L., Oettgen, P., et al. (2008). Engineering robust and functional vascular networks in vivo with human adult and cord blood-derived progenitor cells. Circulation Research, 103(2), 194–202.

    Article  Google Scholar 

  165. Moon, J. J., Hahn, M. S., Kim, I., Nsiah, B. A., & West, J. L. (2009). Micropatterning of poly(ethylene glycol) diacrylate hydrogels with biomolecules to regulate and guide endothelial morphogenesis. Tissue Engineering Part A, 15(3), 579–585.

    Article  Google Scholar 

  166. Moon, J. J., Saik, J. E., Poché, R. A., Leslie-Barbick, J. E., Lee, S.-H., Smith, A. A., et al. (2010). Biomimetic hydrogels with pro-angiogenic properties. Biomaterials, 31(14), 3840–3847.

    Article  Google Scholar 

  167. Myllyharju, J., & Schipani, E. (2010). Extracellular matrix genes as hypoxia-inducible targets. Cell and Tissue Research, 339(1), 19–29.

    Article  Google Scholar 

  168. Niebruegge, S., Bauwens, C. L., Peerani, R., Thavandiran, N., Masse, S., Sevaptisidis, E., et al. (2009). Generation of human embryonic stem cell-derived mesoderm and cardiac cells using size-specified aggregates in an oxygen-controlled bioreactor. Biotechnology and Bioengineering, 102(2), 493–507.

    Article  Google Scholar 

  169. Oppegard, S. C., Blake, A. J., Williams, J. C., & Eddington, D. T. (2010). Precise control over the oxygen conditions within the Boyden chamber using a microfabricated insert. Lab on a Chip, 10(18), 2366–2373.

    Article  Google Scholar 

  170. Ottino, P., Finley, J., Rojo, E., Ottlecz, A., Lambrou, G. N., Bazan, H. E., et al. (2004). Hypoxia activates matrix metalloproteinase expression and the VEGF system in monkey choroid-retinal endothelial cells: Involvement of cytosolic phospholipase A2 activity. Molecular Vision, 10, 341–350.

    Google Scholar 

  171. Papandreou, I., Cairns, R. A., Fontana, L., Lim, A. L., & Denko, N. C. (2006). HIF-1 mediates adaptation to hypoxia by actively downregulating mitochondrial oxygen consumption. Cell Metabolism, 3(3), 187–197.

    Article  Google Scholar 

  172. Papandreou, I., Lim, A. L., Laderoute, K., & Denko, N. C. (2008). Hypoxia signals autophagy in tumor cells via AMPK activity, independent of HIF-1, BNIP3, and BNIP3L. Cell Death and Differentiation, 15(10), 1572–1581.

    Article  Google Scholar 

  173. Park, K. M., & Gerecht, S. (2014). Hypoxia-inducible hydrogels. Nature Communications, 5, 12.

    Google Scholar 

  174. Park, T. G., & Hoffman, A. S. (1992). Synthesis and characterization of pH- and or temperature-sensitive hydrogels. Journal of Applied Polymer Science, 46(4), 659–671.

    Article  Google Scholar 

  175. Parmar, K., Mauch, P., Vergilio, J. A., Sackstein, R., & Down, J. D. (2007). Distribution of hematopoietic stem cells in the bone marrow according to regional hypoxia. Proceedings of the National Academy of Sciences of the United States of America, 104(13), 5431–5436.

    Article  ADS  Google Scholar 

  176. Phelps, E. A., Landazuri, N., Thule, P. M., Taylor, W. R., & Garcia, A. J. (2009). Bioartificial matrices for therapeutic vascularization. Proceedings of the National Academy of Sciences, 107(8), 3323–3328.

    Article  ADS  Google Scholar 

  177. Phillips, P. G., Birnby, L. M., & Narendran, A. (1995). Hypoxia induces capillary network formation in cultured bovine pulmonary microvessel endothelial cells. The American Journal of Physiology, 268(5 Pt 1), L789–L800.

    Google Scholar 

  178. Pierschbacher, M. D., & Ruoslahti, E. (1984). Cell attachment activity of fibronectin can be duplicated by small synthetic fragments of the molecule. Nature, 309(5963), 30–33.

    Article  ADS  Google Scholar 

  179. Pollard, P. J., Loenarz, C., Mole, D. R., McDonough, M. A., Gleadle, J. M., Schofield, C. J., et al. (2008). Regulation of Jumonji-domain-containing histone demethylases by hypoxia-inducible factor (HIF)-1alpha. The Biochemical Journal, 416(3), 387–394.

    Article  Google Scholar 

  180. Popel, A. S. (1989). Theory of oxygen transport to tissue. Critical Reviews in Biomedical Engineering, 17(3), 257–321.

    Google Scholar 

  181. Prado-Lopez, S., Conesa, A., Arminan, A., Martinez-Losa, M., Escobedo-Lucea, C., Gandia, C., et al. (2010). Hypoxia promotes efficient differentiation of human embryonic stem cells to functional endothelium. Stem Cells, 28, 407–418.

    Google Scholar 

  182. Prasad, S. M., Czepiel, M., Cetinkaya, C., Smigielska, K., Weli, S. C., Lysdahl, H., et al. (2009). Continuous hypoxic culturing maintains activation of Notch and allows long-term propagation of human embryonic stem cells without spontaneous differentiation. Cell Proliferation, 42(1), 63–74.

    Article  Google Scholar 

  183. Radisic, M., Deen, W., Langer, R., & Vunjak-Novakovic, G. (2005). Mathematical model of oxygen distribution in engineered cardiac tissue with parallel channel array perfused with culture medium containing oxygen carriers. American Journal of Physiology. Heart and Circulatory Physiology, 288(3), H1278–H1289.

    Article  Google Scholar 

  184. Risau, W. (1997). Mechanisms of angiogenesis. Nature, 386(6626), 671–674.

    Article  ADS  Google Scholar 

  185. Risau, W., & Flamme, I. (1995). Vasculogenesis. Annual Review of Cell and Developmental Biology, 11, 73–91.

    Article  Google Scholar 

  186. Robins, S. P. (2007). Biochemistry and functional significance of collagen cross-linking. Biochemical Society Transactions, 35(5), 849–852.

    Article  Google Scholar 

  187. Rodenhizer, D., Gaude, E., Cojocari, D., Mahadevan, R., Frezza, C., Wouters, B. G., et al. (2016). A three-dimensional engineered tumour for spatial snapshot analysis of cell metabolism and phenotype in hypoxic gradients. Nature Materials, 15(2), 227.

    Article  ADS  Google Scholar 

  188. Rodesch, F., Simon, P., Donner, C., & Jauniaux, E. (1992). Oxygen measurements in endometrial and trophoblastic tissues during early pregnancy. Obstetrics and Gynecology, 80(2), 283–285.

    Google Scholar 

  189. Roeder, B. A., Kokini, K., Sturgis, J. E., Robinson, J. P., & Voytik-Harbin, S. L. (2002). Tensile mechanical properties of three-dimensional type I collagen extracellular matrices with varied microstructure. Journal of Biomechanical Engineering, 124(2), 214–222.

    Article  Google Scholar 

  190. Romer, L. H., Birukov, K. G., & Garcia, J. G. (2006). Focal adhesions: Paradigm for a signaling nexus. Circulation Research, 98(5), 606–616.

    Article  Google Scholar 

  191. 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(12), 3215–3220.

    Article  ADS  Google Scholar 

  192. Sage, E. H., & Vernon, R. B. (1994). Regulation of angiogenesis by extracellular matrix: The growth and the glue. Journal of Hypertension, 12(suppl. 10), S145–S152.

    Google Scholar 

  193. Saunders, W. B., Bayless, K. J., & Davis, G. E. (2005). MMP-1 activation by serine proteases and MMP-10 induces human capillary tubular network collapse and regression in 3D collagen matrices. Journal of Cell Science, 118(Pt 10), 2325–2340.

    Article  Google Scholar 

  194. Scott, C., Lyons, T. W., Bekker, A., Shen, Y., Poulton, S. W., Chu, X., et al. (2008). Tracing the stepwise oxygenation of the Proterozoic ocean. Nature, 452(7186), 456–459.

    Article  ADS  Google Scholar 

  195. Segura, I., Serrano, A., De Buitrago, G. G., Gonzalez, M. A., Abad, J. L., Claveria, C., et al. (2002). Inhibition of programmed cell death impairs in vitro vascular-like structure formation and reduces in vivo angiogenesis. The FASEB Journal, 16(8), 833–841.

    Article  Google Scholar 

  196. Seliktar, D., Zisch, A. H., Lutolf, M. P., Wrana, J. L., & Hubbel, J. A. (2004). MMP-2 sensitive, VEGF-bearing bioactive hydrogels for promotion of vascular healing. Journal of Biomedical Materials Research - Part A, 68(4), 704–716.

    Article  Google Scholar 

  197. Shaw, A. D., Li, Z., Thomas, Z., & Stevens, C. W. (2002). Assessment of tissue oxygen tension: Comparison of dynamic fluorescence quenching and polarographic electrode technique. Critical Care, 6(1), 76–80.

    Article  Google Scholar 

  198. Shen, Y. H., Shoichet, M. S., & Radisic, M. (2008). Vascular endothelial growth factor immobilized in collagen scaffold promotes penetration and proliferation of endothelial cells. Acta Biomaterialia, 4(3), 477–489.

    Article  Google Scholar 

  199. Shweiki, D., Neeman, M., Itin, A., & Keshet, E. (1995). Induction of vascular endothelial growth factor expression by hypoxia and by glucose deficiency in multicell spheroids: Implications for tumor angiogenesis. Proceedings of the National Academy of Sciences of the United States of America, 92(3), 768–772.

    Article  ADS  Google Scholar 

  200. Sieminski, A. L., Hebbel, R. P., & Gooch, K. J. (2004). The relative magnitudes of endothelial force generation and matrix stiffness modulate capillary morphogenesis in vitro. Experimental Cell Research, 297(2), 574–584.

    Article  Google Scholar 

  201. Sieminski, A. L., Was, A. S., Kim, G., Gong, H., & Kamm, R. D. (2007). The stiffness of three-dimensional ionic self-assembling peptide gels affects the extent of capillary-like network formation. Cell Biochemistry and Biophysics, 49(2), 73–83.

    Article  Google Scholar 

  202. Siggaard-Andersen, O., & Huch, R. (1995). The oxygen status of fetal blood. Acta Anaesthesiologica Scandinavica. Supplementum, 107, 129–135.

    Article  Google Scholar 

  203. Silva, G. A., Czeisler, C., Niece, K. L., Beniash, E., Harrington, D. A., Kessler, J. A., et al. (2004). Selective differentiation of neural progenitor cells by high-epitope density nanofibers. Science, 303(5662), 1352–1355.

    Article  ADS  Google Scholar 

  204. Silver, I. A. (1984). Cellular microenvironment in healing and non-healing wounds. In T. K. Hunt (Ed.), Soft and hard tissue repair (pp. 50–66). New York: Praeger.

    Google Scholar 

  205. Smith, Q., Chan, X. Y., Carmo, A. M., Trempel, M., Saunders, M., & Gerecht, S. (2017). Compliant substratum guides endothelial commitment from human pluripotent stem cells. Science Advances, 3(5), 9.

    Google Scholar 

  206. Sorrell, J. M., Baber, M. A., & Caplan, A. I. (2007). A self-assembled fibroblast-endothelial cell co-culture system that supports in vitro vasculogenesis by both human umbilical vein endothelial cells and human dermal microvascular endothelial cells. Cells, Tissues, Organs, 186(3), 157–168.

    Article  Google Scholar 

  207. Sottile, J., & Hocking, D. C. (2002). Fibronectin polymerization regulates the composition and stability of extracellular matrix fibrils and cell-matrix adhesions. Molecular Biology of the Cell, 13(10), 3546–3559.

    Article  Google Scholar 

  208. Soucy, P. A., & Romer, L. H. (2009). Endothelial cell adhesion, signaling, and morphogenesis in fibroblast-derived matrix. Matrix Biology, 28(5), 273–283.

    Article  Google Scholar 

  209. Springett, R., & Swartz, H. M. (2007). Measurements of oxygen in vivo: Overview and perspectives on methods to measure oxygen within cells and tissues. Antioxidants & Redox Signaling, 9(8), 1295–1301.

    Article  Google Scholar 

  210. Steinlechner-Maran, R., Eberl, T., Kunc, M., Margreiter, R., & Gnaiger, E. (1996). Oxygen dependence of respiration in coupled and uncoupled endothelial cells. The American Journal of Physiology, 271(6 Pt 1), C2053–C2061.

    Article  Google Scholar 

  211. Stephanou, A., Meskaoui, G., Vailhe, B., & Tracqui, P. (2007). The rigidity in fibrin gels as a contributing factor to the dynamics of in vitro vascular cord formation. Microvascular Research, 73(3), 182–190.

    Article  Google Scholar 

  212. Stratman, A. N., Saunders, W. B., Sacharidou, A., Koh, W., Fisher, K. E., Zawieja, D. C., et al. (2009). Endothelial cell lumen and vascular guidance tunnel formation requires MT1-MMP-dependent proteolysis in 3-dimensional collagen matrices. Blood, 114(2), 237–247.

    Article  Google Scholar 

  213. Stupack, D. G., & Cheresh, D. A. (2002). ECM remodeling regulates angiogenesis: Endothelial integrins look for new ligands. Science’s STKE, 2002(119), pe7.

    Article  Google Scholar 

  214. Sun, G., & Chu, C.-C. (2006). Synthesis, characterization of biodegradable dextran-allyl isocyanate-ethylamine/polyethylene glycol-diacrylate hydrogels and their in vitro release of albumin. Carbohydrate Polymers, 65(3), 273–287.

    Article  Google Scholar 

  215. Sun, G., Shen, Y.-I., Ho, C. C., Kusuma, S., & Gerecht, S. (2009). Functional groups affect physical and biological properties of dextran-based hydrogels. Journal of Biomedical Materials Research Part A, 93(3), 1080–1090.

    Google Scholar 

  216. Sun, G. M., Zhang, X. Z., & Chu, C. C. (2007). Formulation and characterization of chitosan-based hydrogel films having both temperature and pH sensitivity. Journal of Materials Science. Materials in Medicine, 18(8), 1563–1577.

    Article  Google Scholar 

  217. Tajima, R., Kawaguchi, N., Horino, Y., Takahashi, Y., Toriyama, K., Inou, K., et al. (2001). Hypoxic enhancement of type IV collagen secretion accelerates adipose conversion of 3T3-L1 fibroblasts. Biochimica et Biophysica Acta, 1540(3), 179–187.

    Article  Google Scholar 

  218. Thurston, G., Suri, C., Smith, K., McClain, J., Sato, T. N., Yancopoulos, G. D., et al. (1999). Leakage-resistant blood vessels in mice transgenically overexpressing angiopoietin-1. Science, 286(5449), 2511–2514.

    Article  Google Scholar 

  219. Timmermans, F., Plum, J., Yoder, M. C., Ingram, D. A., Vandekerckhove, B., & Case, J. (2009). Endothelial progenitor cells: Identity defined? Journal of Cellular and Molecular Medicine, 13(1), 87–102.

    Article  Google Scholar 

  220. Toh, Y. C., Zhang, C., Zhang, J., Khong, Y. M., Chang, S., Samper, V. D., et al. (2007). A novel 3D mammalian cell perfusion-culture system in microfluidic channels. Lab on a Chip, 7(3), 302–309.

    Article  Google Scholar 

  221. Toole, B. P. (2001). Hyaluronan in morphogenesis. Seminars in Cell & Developmental Biology, 12(2), 79–87.

    Article  Google Scholar 

  222. Toole, B. P. (2004). Hyaluronan: From extracellular glue to pericellular cue. Nature Reviews. Cancer, 4(7), 528–539.

    Article  Google Scholar 

  223. Tsai, A. G., Johnson, P. C., & Intaglietta, M. (2003). Oxygen gradients in the microcirculation. Physiological Reviews, 83(3), 933–963.

    Article  Google Scholar 

  224. Tsang, K. M., Hyun, J. S., Cheng, K. T., Vargas, M., Mehta, D., Ushio-Fukai, M., et al. (2017). Embryonic stem cell differentiation to functional arterial endothelial cells through sequential activation of ETV2 and NOTCH1 signaling by HIF1 alpha. Stem Cell Reports, 9(3), 796–806.

    Article  Google Scholar 

  225. Urbich, C., & Dimmeler, S. (2004). Endothelial progenitor cells: Characterization and role in vascular biology. Circulation Research, 95(4), 343–353.

    Article  Google Scholar 

  226. Urbich, C., Heeschen, C., Aicher, A., Sasaki, K., Bruhl, T., Farhadi, M. R., et al. (2005). Cathepsin L is required for endothelial progenitor cell-induced neovascularization. Nature Medicine, 11(2), 206–213.

    Article  Google Scholar 

  227. Ushio-Fukai, M., & Nakamura, Y. (2008). Reactive oxygen species and angiogenesis: NADPH oxidase as target for cancer therapy. Cancer Letters, 266(1), 37–52.

    Article  Google Scholar 

  228. Vega, S. L., Kwon, M. Y., Song, K. H., Wang, C., Mauck, R. L., Han, L., et al. (2018). Combinatorial hydrogels with biochemical gradients for screening 3D cellular microenvironments. Nature Communications, 9, 10.

    Article  Google Scholar 

  229. Vo, E., Hanjaya-Putra, D., Zha, Y., Kusuma, S., & Gerecht, S. (2010). Smooth-muscle-like cells derived from human embryonic stem cells support and augment cord-like structures in vitro. Stem Cell Reviews, 6, 237–247.

    Article  Google Scholar 

  230. Walls, J. R., Coultas, L., Rossant, J., & Henkelman, R. M. (2008). Three-dimensional analysis of vascular development in the mouse embryo. PLoS One, 3(8), e2853.

    Article  ADS  Google Scholar 

  231. Walter, D. H., Rittig, K., Bahlmann, F. H., Kirchmair, R., Silver, M., Murayama, T., et al. (2002). Statin therapy accelerates reendothelialization: A novel effect involving mobilization and incorporation of bone marrow-derived endothelial progenitor cells. Circulation, 105(25), 3017–3024.

    Article  Google Scholar 

  232. Wanjare, M., Kusuma, S., & Gerecht, S. (2014). Defining differences among perivascular cells derived from human pluripotent stem cells. Stem Cell Reports, 2(5), 561–575.

    Article  Google Scholar 

  233. Ward, J. P. (2008). Oxygen sensors in context. Biochimica et Biophysica Acta, 1777(1), 1–14.

    Article  Google Scholar 

  234. Webster, K. A. (2006). Puma joins the battery of BH3-only proteins that promote death and infarction during myocardial ischemia. American Journal of Physiology. Heart and Circulatory Physiology, 291(1), H20–H22.

    Article  MathSciNet  Google Scholar 

  235. Werner, N., Junk, S., Laufs, U., Link, A., Walenta, K., Bohm, M., et al. (2003). Intravenous transfusion of endothelial progenitor cells reduces neointima formation after vascular injury. Circulation Research, 93(2), e17–e24.

    Article  Google Scholar 

  236. Wijelath, E. S., Rahman, S., Namekata, M., Murray, J., Nishimura, T., Mostafavi-Pour, Z., et al. (2006). Heparin-II domain of fibronectin is a vascular endothelial growth factor-binding domain: Enhancement of VEGF biological activity by a singular growth factor/matrix protein synergism. Circulation Research, 99(8), 853–860.

    Article  Google Scholar 

  237. Williams, S. E., Wootton, P., Mason, H. S., Bould, J., Iles, D. E., Riccardi, D., et al. (2004). Hemoxygenase-2 is an oxygen sensor for a calcium-sensitive potassium channel. Science, 306(5704), 2093–2097.

    Article  ADS  Google Scholar 

  238. Wolburg, H., & Lippoldt, A. (2002). Tight junctions of the blood-brain barrier: Development, composition and regulation. Vascular Pharmacology, 38(6), 323–337.

    Article  Google Scholar 

  239. Wolin, M. S., Ahmad, M., & Gupte, S. A. (2005). Oxidant and redox signaling in vascular oxygen sensing mechanisms: Basic concepts, current controversies, and potential importance of cytosolic NADPH. American Journal of Physiology. Lung Cellular and Molecular Physiology, 289(2), L159–L173.

    Article  Google Scholar 

  240. Xu, W., Koeck, T., Lara, A. R., Neumann, D., DiFilippo, F. P., Koo, M., et al. (2007). Alterations of cellular bioenergetics in pulmonary artery endothelial cells. Proceedings of the National Academy of Sciences of the United States of America, 104(4), 1342–1347.

    Article  ADS  Google Scholar 

  241. Yamakawa, M., Liu, L. X., Date, T., Belanger, A. J., Vincent, K. A., Akita, G. Y., et al. (2003). Hypoxia-inducible factor-1 mediates activation of cultured vascular endothelial cells by inducing multiple angiogenic factors. Circulation Research, 93(7), 664–673.

    Article  Google Scholar 

  242. Yoon, C. H., Hur, J., Oh, I. Y., Park, K. W., Kim, T. Y., Shin, J. H., et al. (2006). Intercellular adhesion molecule-1 is upregulated in ischemic muscle, which mediates trafficking of endothelial progenitor cells. Arteriosclerosis, Thrombosis, and Vascular Biology, 26(5), 1066–1072.

    Article  Google Scholar 

  243. Yoshida, Y., Takahashi, K., Okita, K., Ichisaka, T., & Yamanaka, S. (2009). Hypoxia enhances the generation of induced pluripotent stem cells. Cell Stem Cell, 5(3), 237–241.

    Article  Google Scholar 

  244. Yung, C. W., Wu, L. Q., Tullman, J. A., Payne, G. F., Bentley, W. E., & Barbari, T. A. (2007). Transglutaminase crosslinked gelatin as a tissue engineering scaffold. Journal of Biomedical Materials Research Part A, 83A(4), 1039–1046.

    Article  Google Scholar 

  245. Zhang, H., Bosch-Marce, M., Shimoda, L. A., Tan, Y. S., Baek, J. H., Wesley, J. B., et al. (2008). Mitochondrial autophagy is an HIF-1-dependent adaptive metabolic response to hypoxia. The Journal of Biological Chemistry, 283(16), 10892–10903.

    Article  Google Scholar 

  246. Zhang, X., Liu, L., Wei, X., Tan, Y. S., Tong, L., Chang Bs, R., et al. (2010). Impaired angiogenesis and mobilization of circulating angiogenic cells in HIF-1alpha heterozygous-null mice after burn wounding. Wound Repair and Regeneration, 18, 193–201.

    Article  Google Scholar 

  247. Zhou, X., Rowe, R. G., Hiraoka, N., George, J. P., Wirtz, D., Mosher, D. F., et al. (2008). Fibronectin fibrillogenesis regulates three-dimensional neovessel formation. Genes and Development, 22(9), 1231–1243.

    Article  Google Scholar 

  248. Zisch, A. H., Lutolf, M. P., & Hubbell, J. A. (2003). Biopolymeric delivery matrices for angiogenic growth factors. Cardiovascular Pathology, 12(6), 295–310.

    Article  Google Scholar 

  249. Zisch, A. H., Lutolf, M. P., Ehrbar, M., Raeber, G. P., Rizzi, S. C., Davies, N., et al. (2003). Cell-demanded release of VEGF from synthetic, biointeractive cell ingrowth matrices for vascularized tissue growth. The FASEB Journal, 17(15), 2260–2262.

    Article  Google Scholar 

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Acknowledgments

We would like to acknowledge funding from various agencies that supported our studies throughout the years, primarily the American Heart Association, the Maryland Stem Cell Research Fund, the National Science Foundation, and the National Institutes of Health.

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Blatchley, M.R., Abaci, H.E., Hanjaya-Putra, D., Gerecht, S. (2018). Hypoxia and Matrix Manipulation for Vascular Engineering. In: Gerecht, S. (eds) Biophysical Regulation of Vascular Differentiation and Assembly. Biological and Medical Physics, Biomedical Engineering. Springer, Cham. https://doi.org/10.1007/978-3-319-99319-5_4

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