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Microscale Technologies for Engineering Complex Tissue Structures

  • Charles W. Peak
  • Lauren Cross
  • Ankur Singh
  • Akhilesh K. GaharwarEmail author

Abstract

Engineered tissue scaffolds aim to reproduce the body’s architectural and geometrical intricacies, including vital cell–cell interactions. These scaffolds serve as synthetic extracellular matrices that organize the embedded cells into a three-dimensional (3D) architecture and present them with stimuli for their growth and maturation. Tissue engineering techniques have been applied to many types of tissues; however, numerous challenges regarding their development still remain. These challenges include our inability to generate a functional vasculature that can supply the tissue with nutrients and oxygen and the inability to mimic the complex cell–microenvironmental interactions that regulate the formation of a functional tissue. This chapter focuses on the most recent developments in the field of microfabrication technologies to design vascularized tissue constructs. In particular, we discuss emerging bottom-up approaches to design complex macroscale structures, examine their current limitations, and conclude with future directions in designing more complex tissue architecture.

Keywords

Microscale technologies Tissue engineering Vascularized tissues Bioprinting Complex tissues 

References

  1. 1.
    Langer R, Vacanti JP (1993) Tissue engineering. Science 260:920–926CrossRefGoogle Scholar
  2. 2.
    Khademhosseini A, Vacanti JP, Langer R (2009) Progress in tissue engineering. Sci Am 300:64–71CrossRefGoogle Scholar
  3. 3.
    Langer R, Tirrell DA (2004) Designing materials for biology and medicine. Nature 428:487–492CrossRefGoogle Scholar
  4. 4.
    Gaharwar AK, Peppas NA, Khademhosseini A (2014) Nanocomposite hydrogels for biomedical applications. Biotechnol Bioeng 111:441–453CrossRefGoogle Scholar
  5. 5.
    Singh A, Peppas NA (2014) Hydrogels and scaffolds for immunomodulation. Adv Mater 26:6530–6541CrossRefGoogle Scholar
  6. 6.
    Place ES, Evans ND, Stevens MM (2009) Complexity in biomaterials for tissue engineering. Nat Mater 8:457–470CrossRefGoogle Scholar
  7. 7.
    Khademhosseini A, Langer R, Borenstein J, Vacanti JP (2006) Microscale technologies for tissue engineering and biology. Proc Natl Acad Sci U S A 103:2480CrossRefGoogle Scholar
  8. 8.
    Griffith LG, Swartz MA (2006) Capturing complex 3D tissue physiology in vitro. Nat Rev Mol Cell Biol 7:211–224CrossRefGoogle Scholar
  9. 9.
    Kaully T, Kaufman-Francis K, Lesman A, Levenberg S (2009) Vascularization – the conduit to viable engineered tissues. Tissue Eng Part B Rev 15:159–169CrossRefGoogle Scholar
  10. 10.
    Lovett M, Lee K, Edwards A, Kaplan DL (2009) Vascularization strategies for tissue engineering. Tissue Eng Part B Rev 15:353–370CrossRefGoogle Scholar
  11. 11.
    Phelps EA, Garcia A (2010) Engineering more than a cell: vascularization strategies in tissue engineering. Curr Opin Biotechnol 21:704–709CrossRefGoogle Scholar
  12. 12.
    Naito Y, Shinoka T, Duncan D, Hibino N, Solomon D, Cleary M et al (2011) Vascular tissue engineering: towards the next generation vascular grafts. Adv Drug Deliv Rev 63:312–323CrossRefGoogle Scholar
  13. 13.
    Santos MI, Reis RL (2010) Vascularization in bone tissue engineering: physiology, current strategies, major hurdles and future challenges. Macromol Biosci 10:12–27CrossRefGoogle Scholar
  14. 14.
    Khademhosseini A, Langer R (2007) Microengineered hydrogels for tissue engineering. Biomaterials 28:5087–5092CrossRefGoogle Scholar
  15. 15.
    Zorlutuna P, Annabi N, Camci-Unal G, Nikkhah M, Cha JM, Nichol JW et al (2012) Microfabricated biomaterials for engineering 3D tissues. Adv Mater 24:1782–1804CrossRefGoogle Scholar
  16. 16.
    Patel RG, Purwada A, Cerchietti L, Inghirami G, Melnick A, Gaharwar AK et al (2014) Microscale bioadhesive hydrogel arrays for cell engineering applications. Cell Mol Bioeng 7(3):394–408CrossRefGoogle Scholar
  17. 17.
    Lanza RP, Vacanti J (2007) Principles of tissue engineering. Academic Press, New YorkGoogle Scholar
  18. 18.
    Giuliani M, Moritz W, Bodmer E, Dindo D, Kugelmeier P, Lehmann R et al (2005) Central necrosis in isolated hypoxic human pancreatic islets: evidence for postisolation ischemia. Cell Transplant 14:67–76CrossRefGoogle Scholar
  19. 19.
    Larrea X, Buechler P, Büchler P, Buchler P (2009) A transient diffusion model of the cornea for the assessment of oxygen diffusivity and consumption. Invest Ophthalmol Vis Sci 50:1076–1080CrossRefGoogle Scholar
  20. 20.
    Cook CA, Hahn KC, Morrissette-McAlmon JBF, Grayson WL (2015) Oxygen delivery from hyperbarically loaded microtanks extends cell viability in anoxic environments. Biomaterials 52:376–384CrossRefGoogle Scholar
  21. 21.
    Risau W, Flamme I (1995) Vasculogenesis. Annu Rev Cell Dev Biol 11:73–91CrossRefGoogle Scholar
  22. 22.
    Risau W (1997) Mechanisms of angiogenesis. Nature 386:671–674CrossRefGoogle Scholar
  23. 23.
    Folkman J, Shing Y (1992) Angiogenesis. J Biol Chem 267:10931Google Scholar
  24. 24.
    Jain RK (2003) Molecular regulation of vessel maturation. Nat Med 9:685–693CrossRefGoogle Scholar
  25. 25.
    Pepper MS (1997) Transforming growth factor-beta: vasculogenesis, angiogenesis, and vessel wall integrity. Cytokine Growth Factor Rev 8:21–43CrossRefGoogle Scholar
  26. 26.
    Flamme I, Frölich T, Risau W (1997) Molecular mechanisms of vasculogenesis and embryonic angiogenesis. J Cell Physiol 173:206–210CrossRefGoogle Scholar
  27. 27.
    Patan S (2000) Vasculogenesis and angiogenesis as mechanisms of vascular network formation, growth and remodeling. J Neurooncol 50:1–15CrossRefGoogle Scholar
  28. 28.
    Singer AJ, Clark R (1999) Cutaneous wound healing. N Engl J Med 341:738–746CrossRefGoogle Scholar
  29. 29.
    Brown LF, Yeo KT, Berse B, Yeo TK, Senger DR, Dvorak HF et al (1992) Expression of vascular permeability factor (vascular endothelial growth factor) by epidermal keratinocytes during wound healing. J Exp Med 176:1375CrossRefGoogle Scholar
  30. 30.
    Seghezzi G, Patel S, Ren CJ, Gualandris A, Pintucci G, Robbins ES et al (1998) Fibroblast growth factor-2 (FGF-2) induces vascular endothelial growth factor (VEGF) expression in the endothelial cells of forming capillaries: an autocrine mechanism contributing to angiogenesis. J Cell Biol 141:1659CrossRefGoogle Scholar
  31. 31.
    Sato Y, Endo H, Okuyama H, Takeda T, Iwahashi H, Imagawa A et al (2011) Cellular hypoxia of pancreatic β-cells due to high levels of oxygen consumption for insulin secretion in vitro. J Biol Chem 286:12524–12532CrossRefGoogle Scholar
  32. 32.
    Nichol JW, Khademhosseini A (2009) Modular tissue engineering: engineering biological tissues from the bottom up. Soft Matter 5:1312–1319CrossRefGoogle Scholar
  33. 33.
    Griffith LG, Naughton G (2002) Tissue engineering – current challenges and expanding opportunities. Science 295:1009CrossRefGoogle Scholar
  34. 34.
    West JL, Moon JJ (2008) Vascularization of engineered tissues: approaches to promote angiogenesis in biomaterials. Curr Top Med Chem 8:300–310CrossRefGoogle Scholar
  35. 35.
    Khan OF, Sefton MV (2011) Endothelialized biomaterials for tissue engineering applications in vivo. Trends Biotechnol 29(8):379–387Google Scholar
  36. 36.
    Rouwkema J, Rivron N, van Blitterswijk C (2008) Vascularization in tissue engineering. Trends Biotechnol 26:434–441CrossRefGoogle Scholar
  37. 37.
    Sukmana I, Vermette P (2010) Polymer fibers as contact guidance to orient microvascularization in a 3D environment. J Biomed Mater Res A 92A:1587–1597Google Scholar
  38. 38.
    Gaharwar AK, Nikkhah M, Sant S, Khademhosseini A (2015) Anisotropic poly (glycerol sebacate)-poly (ϵ-caprolactone) electrospun fibers promote endothelial cell guidance. Biofabrication 7:015001CrossRefGoogle Scholar
  39. 39.
    Sant S, Iyer D, Gaharwar AK, Patel A, Khademhosseini A (2013) Effect of biodegradation and de novo matrix synthesis on the mechanical properties of valvular interstitial cell-seeded polyglycerol sebacate-polycaprolactone scaffolds. Acta Biomater 9:5963–5973CrossRefGoogle Scholar
  40. 40.
    Patel ZS, Mikos AG (2004) Angiogenesis with biomaterial-based drug-and cell-delivery systems. J Biomater Sci Polym Ed 15:701–726CrossRefGoogle Scholar
  41. 41.
    Asahara T, Takahashi T, Masuda H, Kalka C, Chen D, Iwaguro H et al (1999) VEGF contributes to postnatal neovascularization by mobilizing bone marrow-derived endothelial progenitor cells. EMBO J 18:3964–3972CrossRefGoogle Scholar
  42. 42.
    Silva EA, Mooney DJ (2010) Effects of VEGF temporal and spatial presentation on angiogenesis. Biomaterials 31:1235–1241CrossRefGoogle Scholar
  43. 43.
    Asahara T, Chen D, Takahashi T, Fujikawa K, Kearney M, Magner M et al (1998) Tie2 receptor ligands, angiopoietin-1 and angiopoietin-2, modulate VEGF-induced postnatal neovascularization. Circ Res 83:233CrossRefGoogle Scholar
  44. 44.
    Grunewald M, Avraham I, Dor Y, Bachar-Lustig E, Itin A, Yung S et al (2006) VEGF-induced adult neovascularization: recruitment, retention, and role of accessory cells. Cell 124:175–189CrossRefGoogle Scholar
  45. 45.
    Ferrara N, Gerber HP, LeCouter J (2003) The biology of VEGF and its receptors. Nat Med 9:669–676CrossRefGoogle Scholar
  46. 46.
    Salcedo R, Wasserman K, Young HA, Grimm MC, Howard O, Anver MR et al (1999) Vascular endothelial growth factor and basic fibroblast growth factor induce expression of CXCR4 on human endothelial cells: in vivo neovascularization induced by stromal-derived factor-1 {alpha}. Am J Pathol 154:1125CrossRefGoogle Scholar
  47. 47.
    Tabata Y, Ikada Y (1999) Vascularization effect of basic fibroblast growth factor released from gelatin hydrogels with different biodegradabilities. Biomaterials 20:2169–2175CrossRefGoogle Scholar
  48. 48.
    Presta M, Dell'Era P, Mitola S, Moroni E, Ronca R, Rusnati M (2005) Fibroblast growth factor/fibroblast growth factor receptor system in angiogenesis. Cytokine Growth Factor Rev 16:159–178CrossRefGoogle Scholar
  49. 49.
    Bikfalvi A, Klein S, Pintucci G, Rifkin DB (1997) Biological roles of fibroblast growth factor-2. Endocr Rev 18:26Google Scholar
  50. 50.
    Roberts AB (2000) Molecular and cell biology of TGF. Miner Electrolyte Metab 24:111–119CrossRefGoogle Scholar
  51. 51.
    Bergsten E, Uutela M, Li X, Pietras K, Östman A, Heldin CH et al (2001) PDGF-D is a specific, protease-activated ligand for the PDGF -receptor. Nat Cell Biol 3:512–516CrossRefGoogle Scholar
  52. 52.
    LaRochelle WJ, Jeffers M, McDonald WF, Chillakuru RA, Giese NA, Lokker NA et al (2001) PDGF-D, a new protease-activated growth factor. Nat Cell Biol 3:517–521CrossRefGoogle Scholar
  53. 53.
    Stiles CD (1983) The molecular biology of platelet-derived growth factor. Cell 33:653CrossRefGoogle Scholar
  54. 54.
    Koblizek TI, Weiss C, Yancopoulos GD, Deutsch U, Risau W (1998) Angiopoietin-1 induces sprouting angiogenesis in vitro. Curr Biol 8:529–532CrossRefGoogle Scholar
  55. 55.
    Melero-Martin JM, De Obaldia ME, Kang S-Y, Khan ZA, Yuan L, Oettgen P et al (2008) Engineering robust and functional vascular networks in vivo with human adult and cord blood-derived progenitor cells. Circ Res 103:194–202CrossRefGoogle Scholar
  56. 56.
    Levenberg S, Rouwkema J, Macdonald M, Garfein ES, Kohane DS, Darland DC et al (2005) Engineering vascularized skeletal muscle tissue. Nat Biotech 23:879–884CrossRefGoogle Scholar
  57. 57.
    Phelps EA, Landázuri N, Thulé PM, Taylor WR, García AJ (2010) Bioartificial matrices for therapeutic vascularization. Proc Natl Acad Sci 107:3323–3328CrossRefGoogle Scholar
  58. 58.
    Vozzi G, Flaim C, Ahluwalia A, Bhatia S (2003) Fabrication of PLGA scaffolds using soft lithography and microsyringe deposition. Biomaterials 24:2533–2540CrossRefGoogle Scholar
  59. 59.
    Wang GJ, Hsueh CC, Hsu S, Hung HS (2007) Fabrication of PLGA microvessel scaffolds with circular microchannels using soft lithography. J Micromech Microeng 17:2000CrossRefGoogle Scholar
  60. 60.
    Sodha S, Wall K, Redenti S, Klassen H, Young MJ, Tao SL (2011) Microfabrication of a three-dimensional polycaprolactone thin-film scaffold for retinal progenitor cell encapsulation. J Biomater Sci Polym Ed 22(4–6):443–456CrossRefGoogle Scholar
  61. 61.
    Armani DK, Liu C (2000) Microfabrication technology for polycaprolactone, a biodegradable polymer. J Micromech Microeng 10:80CrossRefGoogle Scholar
  62. 62.
    Bettinger CJ, Orrick B, Misra A, Langer R, Borenstein JT (2006) Microfabrication of poly (glycerol-sebacate) for contact guidance applications. Biomaterials 27:2558–2565CrossRefGoogle Scholar
  63. 63.
    Guillemette MD, Park H, Hsiao JC, Jain SR, Larson BL, Langer R et al (2010) Combined technologies for microfabricating elastomeric cardiac tissue engineering scaffolds. Macromol Biosci 10(11):1330–1337CrossRefGoogle Scholar
  64. 64.
    Bettinger CJ, Weinberg EJ, Kulig KM, Vacanti JP, Wang Y, Borenstein JT et al (2006) Three dimensional microfluidic tissue engineering scaffolds using a flexible biodegradable polymer. Adv Mater 18:165–169CrossRefGoogle Scholar
  65. 65.
    Neeley WL, Redenti S, Klassen H, Tao S, Desai T, Young MJ et al (2008) A microfabricated scaffold for retinal progenitor cell grafting. Biomaterials 29:418–426CrossRefGoogle Scholar
  66. 66.
    Zhang H, Patel A, Gaharwar AK, Mihaila SM, Iviglia GI, Mukundan S et al (2013) Hyperbranched polyester hydrogels with controlled drug release and cell adhesion properties. Biomacromolecules 14(5):1299–1310Google Scholar
  67. 67.
    Nikkhah M, Eshak N, Zorlutuna P, Annabi N, Castello M, Kim K et al (2012) Directed endothelial cell morphogenesis in micropatterned gelatin methacrylate hydrogels. Biomaterials 33:9009CrossRefGoogle Scholar
  68. 68.
    Nichol JW, Koshy ST, Bae H, Hwang CM, Yamanlar S, Khademhosseini A (2010) Cell-laden microengineered gelatin methacrylate hydrogels. Biomaterials 31:5536–5544CrossRefGoogle Scholar
  69. 69.
    Oh J, Kim K, Won S, Cha C, Gaharwar A, Selimovic S et al (2013) Microfluidic fabrication of cell adhesive chitosan microtubes. Biomed Microdevices 15(3):465–472Google Scholar
  70. 70.
    Mihaila SM, Gaharwar AK, Reis RL, Marques AP, Gomes ME, Khademhosseini A (2013) Photocrosslinkable kappa-carrageenan hydrogels for tissue engineering applications. Adv Healthc Mater 2(6):895–907Google Scholar
  71. 71.
    Chiu Y-C, Larson JC, Perez-Luna VH, Brey EM (2009) Formation of microchannels in poly(ethylene glycol) hydrogels by selective degradation of patterned microstructures. Chem Mater 21:1677–1682CrossRefGoogle Scholar
  72. 72.
    Heckele M, Schomburg W (2004) Review on micro molding of thermoplastic polymers. J Micromech Microeng 14:R1CrossRefGoogle Scholar
  73. 73.
    Kim E, Xia Y, Whitesides GM (1996) Micromolding in capillaries: applications in materials science. J Am Chem Soc 118:5722–5731CrossRefGoogle Scholar
  74. 74.
    Fidkowski C, Kaazempur-Mofrad MR, Borenstein J, Vacanti JP, Langer R, Wang Y (2005) Endothelialized microvasculature based on a biodegradable elastomer. Tissue Eng 11:302–309CrossRefGoogle Scholar
  75. 75.
    Zheng Y, Henderson PW, Choi NW, Bonassar LJ, Spector JA, Stroock AD (2011) Microstructured templates for directed growth and vascularization of soft tissue in vivo. Biomaterials 32:5391–5401CrossRefGoogle Scholar
  76. 76.
    Diez M, Schulte VA, Stefanoni F, Natale CF, Mollica F, Cesa CM et al (2011) Molding micropatterns of elasticity on PEG based hydrogels to control cell adhesion and migration. Adv Eng Mater 13(10):B395–B404Google Scholar
  77. 77.
    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. J Biomed Mater Res B Appl Biomater 81B:462–468CrossRefGoogle Scholar
  78. 78.
    Vozzi G, Previti A, De Rossi D, Ahluwalia A (2002) Microsyringe-based deposition of two-dimensional and three-dimensional polymer scaffolds with a well-defined geometry for application to tissue engineering. Tissue Eng 8:1089–1098CrossRefGoogle Scholar
  79. 79.
    Lewis JA (2006) Direct ink writing of 3D functional materials. Adv Funct Mater 16:2193–2204CrossRefGoogle Scholar
  80. 80.
    Lewis JA, Gratson GM (2004) Direct writing in three dimensions. Mater Today 7:32–39CrossRefGoogle Scholar
  81. 81.
    Therriault D, White SR, Lewis JA (2003) Chaotic mixing in three-dimensional microvascular networks fabricated by direct-write assembly. Nat Mater 2:265–271CrossRefGoogle Scholar
  82. 82.
    Therriault D, Shepherd RF, White SR, Lewis JA (2005) Fugitive inks for direct write assembly of three dimensional microvascular networks. Adv Mater 17:395–399CrossRefGoogle Scholar
  83. 83.
    Wu W, DeConinck A, Lewis JA (2010) Omnidirectional printing of 3D microvascular networks. Adv Mater 23(24):H178–H183Google Scholar
  84. 84.
    Xavier JR, Thakur T, Desai P, Jaiswal MK, Sears N, Cosgriff-Hernandez E et al (2015) Bioactive nanoengineered hydrogels for bone tissue engineering: a growth-factor-free approach. ACS Nano 9:3109–3118CrossRefGoogle Scholar
  85. 85.
    Whitesides GM (2006) The origins and the future of microfluidics. Nature 442:368–373CrossRefGoogle Scholar
  86. 86.
    Choi NW, Cabodi M, Held B, Gleghorn JP, Bonassar LJ, Stroock AD (2007) Microfluidic scaffolds for tissue engineering. Nat Mater 6:908–915CrossRefGoogle Scholar
  87. 87.
    Borenstein JT, Terai H, King KR, Weinberg EJ, Kaazempur-Mofrad MR, Vacanti JP (2002) Microfabrication technology for vascularized tissue engineering. Biomed Microdevices 4:167–175CrossRefGoogle Scholar
  88. 88.
    King KR, Wang CCJ, Kaazempur-Mofrad MR, Vacanti JP, Borenstein JT (2004) Biodegradable microfluidics. Adv Mater 16:2007–2012CrossRefGoogle Scholar
  89. 89.
    Borenstein JT, Megley K, Wall K, Pritchard EM, Truong D, Kaplan DL et al (2010) Tissue equivalents based on cell-seeded biodegradable microfluidic constructs. Materials 3:1833–1844CrossRefGoogle Scholar
  90. 90.
    Wang Y, Ameer GA, Sheppard BJ, Langer R (2002) A tough biodegradable elastomer. Nat Biotech 20:602–606CrossRefGoogle Scholar
  91. 91.
    Wang J, Bettinger CJ, Langer RS, Borenstein JT (2010) Biodegradable microfluidic scaffolds for tissue engineering from amino alcohol-based poly (ester amide) elastomers. Organogenesis 6:212CrossRefGoogle Scholar
  92. 92.
    Borenstein J, Tupper M, Mack P, Weinberg E, Khalil A, Hsiao J et al (2010) Functional endothelialized microvascular networks with circular cross-sections in a tissue culture substrate. Biomed Microdevices 12:71–79CrossRefGoogle Scholar
  93. 93.
    Golden AP, Tien J (2007) Fabrication of microfluidic hydrogels using molded gelatin as a sacrificial element. Lab Chip 7:720–725CrossRefGoogle Scholar
  94. 94.
    Miller JS, Stevens KR, Yang MT, Baker BM, Nguyen D-HT, Cohen DM et al (2012) Rapid casting of patterned vascular networks for perfusable engineered three-dimensional tissues. Nat Mater 11(9):768–774CrossRefGoogle Scholar
  95. 95.
    Bellan LM, Pearsall M, Cropek DM, Langer R (2012) A 3D interconnected microchannel network formed in gelatin by sacrificial shellac microfibers. Adv Mater 24:5187–5191CrossRefGoogle Scholar
  96. 96.
    Sakaguchi K, Shimizu T, Horaguchi S, Sekine H, Yamato M, Umezu M et al (2013) In vitro engineering of vascularized tissue surrogates. Sci Rep 3Google Scholar
  97. 97.
    Aubin H, Nichol JW, Hutson CB, Bae H, Sieminski AL, Cropek DM et al (2010) Directed 3D cell alignment and elongation in microengineered hydrogels. Biomaterials 31:6941–6951CrossRefGoogle Scholar
  98. 98.
    Fernandez JG, Khademhosseini A (2010) Micro-masonry: construction of 3D structures by microscale self-assembly. Adv Mater 22:2538–2541CrossRefGoogle Scholar
  99. 99.
    Du Y, Lo E, Ali S, Khademhosseini A (2008) Directed assembly of cell-laden microgels for fabrication of 3D tissue constructs. Proc Natl Acad Sci 105:9522–9527CrossRefGoogle Scholar
  100. 100.
    Du Y, Ghodousi M, Qi H, Haas N, Xiao W, Khademhosseini A. Sequential assembly of cell-laden hydrogel constructs to engineer vascular-like microchannels. Biotechnol Bioeng 108(7):1693–1703Google Scholar
  101. 101.
    Jakab K, Norotte C, Damon B, Marga F, Neagu A, Besch-Williford CL et al (2008) Tissue engineering by self-assembly of cells printed into topologically defined structures. Tissue Eng Part A 14:413–421CrossRefGoogle Scholar
  102. 102.
    Jakab K, Norotte C, Marga F, Murphy K, Vunjak-Novakovic G, Forgacs G (2010) Tissue engineering by self-assembly and bio-printing of living cells. Biofabrication 2:022001CrossRefGoogle Scholar
  103. 103.
    McGuigan AP, Sefton MV (2006) Vascularized organoid engineered by modular assembly enables blood perfusion. Proc Natl Acad Sci 103:11461CrossRefGoogle Scholar
  104. 104.
    Paul A, Hasan A, Kindi HA, Gaharwar AK, Rao VT, Nikkhah M et al (2014) Injectable graphene oxide/hydrogel-based angiogenic gene delivery system for vasculogenesis and cardiac repair. ACS Nano 8:8050–8062CrossRefGoogle Scholar
  105. 105.
    Gaharwar AK, Avery RK, Assmann A, Paul A, McKinley GH, Khademhosseini A et al (2014) Shear-thinning nanocomposite hydrogels for the treatment of hemorrhage. ACS Nano 8:9833–9842CrossRefGoogle Scholar
  106. 106.
    Dvir T, Timko BP, Kohane DS, Langer R (2011) Nanotechnological strategies for engineering complex tissues. Nat Nanotechnol 6:13–22CrossRefGoogle Scholar
  107. 107.
    Gaharwar AK, Schexnailder PJ, Kline BP, Schmidt G (2011) Assessment of using laponite cross-linked poly(ethylene oxide) for controlled cell adhesion and mineralization. Acta Biomater 7:568–577CrossRefGoogle Scholar
  108. 108.
    Gaharwar AK, Schexnailder P, Kaul V, Akkus O, Zakharov D, Seifert S et al (2010) Highly extensible bio-nanocomposite films with direction-dependent properties. Adv Funct Mater 20:429–436CrossRefGoogle Scholar
  109. 109.
    Gaharwar AK, Kishore V, Rivera C, Bullock W, Wu C-J, Akkus O et al (2012) Physically crosslinked nanocomposites from silicate-crosslinked PEO: mechanical properties and osteogenic differentiation of human mesenchymal stem cells. Macromol Biosci 12:779–793CrossRefGoogle Scholar
  110. 110.
    Gaharwar AK, Rivera CP, Wu C-J, Schmidt G (2011) Transparent, elastomeric and tough hydrogels from poly(ethylene glycol) and silicate nanoparticles. Acta Biomater 7:4139–4148CrossRefGoogle Scholar
  111. 111.
    Carrow JK, Gaharwar AK (2015) Bioinspired polymeric nanocomposites for regenerative medicine. Macromol Chem Phys 216:248–264CrossRefGoogle Scholar
  112. 112.
    Schuurman W, Khristov V, Pot MW, van Weeren PR, Dhert WJA, Malda J (2011) Bioprinting of hybrid tissue constructs with tailorable mechanical properties. Biofabrication 3(2):021001CrossRefGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2016

Authors and Affiliations

  • Charles W. Peak
    • 1
  • Lauren Cross
    • 1
  • Ankur Singh
    • 2
  • Akhilesh K. Gaharwar
    • 1
    • 3
    Email author
  1. 1.Department of Biomedical EngineeringTexas A&M UniversityCollege StationUSA
  2. 2.Sibley School of Mechanical and Aerospace EngineeringCornell UniversityIthacaUSA
  3. 3.Department of Materials Science and EngineeringTexas A&M UniversityCollege StationUSA

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