A decade of progress in tissue engineering


Tremendous progress has been achieved in the field of tissue engineering in the past decade. Several major challenges laid down 10 years ago, have been studied, including renewable cell sources, biomaterials with tunable properties, mitigation of host responses, and vascularization. Here we review advancements in these areas and envision directions of further development.

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.

Figure 1
Figure 2: Summary of tissue engineering progress in the past decade.
Figure 3


  1. 1

    Langer, R. & Vacanti, J.P. Tissue engineering. Science 260, 920–926 (1993).

    CAS  PubMed  Google Scholar 

  2. 2

    Khademhosseini, A., Vacanti, J.P. & Langer, R. Progress in tissue engineering. Sci. Am. 300, 64–71 (2009).

    CAS  PubMed  Google Scholar 

  3. 3

    Khademhosseini, A. & Langer, R. Microengineered hydrogels for tissue engineering. Biomaterials 28, 5087–5092 (2007).

    CAS  PubMed  Google Scholar 

  4. 4

    Okita, K., Ichisaka, T. & Yamanaka, S. Generation of germline-competent induced pluripotent stem cells. Nature 448, 313–317 (2007).

    CAS  PubMed  Google Scholar 

  5. 5

    Yu, J. et al. Induced pluripotent stem cell lines derived from human somatic cells. Science 318, 1917–1920 (2007).

    CAS  Google Scholar 

  6. 6

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

  7. 7

    DeForest, C.A., Polizzotti, B.D. & Anseth, K.S. Sequential click reactions for synthesizing and patterning three-dimensional cell microenvironments. Nat. Mater. 8, 659–664 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  8. 8

    DeForest, C.A. & Anseth, K.S. Cytocompatible click-based hydrogels with dynamically tunable properties through orthogonal photoconjugation and photocleavage reactions. Nat. Chem. 3, 925–931 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  9. 9

    Martino, M.M., Briquez, P.S., Ranga, A., Lutolf, M.P. & Hubbell, J.A. Heparin-binding domain of fibrin(ogen) binds growth factors and promotes tissue repair when incorporated within a synthetic matrix. Proc. Natl. Acad. Sci. USA 110, 4563–4568 (2013).

    CAS  PubMed  Google Scholar 

  10. 10

    Pakulska, M.M., Miersch, S. & Shoichet, M.S. Designer protein delivery: From natural to engineered affinity-controlled release systems. Science 351, aac4750 (2016).

    PubMed  Google Scholar 

  11. 11

    Veiseh, O. et al. Size- and shape-dependent foreign body immune response to materials implanted in rodents and non-human primates. Nat. Mater. 14, 643–651 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  12. 12

    Vegas, A.J. et al. Combinatorial hydrogel library enables identification of materials that mitigate the foreign body response in primates. Nat. Biotechnol. 34, 345–352 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  13. 13

    Langer, R. et al. Tissue engineering: biomedical applications. Tissue Eng. 1, 151–161 (1995).

    CAS  PubMed  Google Scholar 

  14. 14

    Vacanti, J.P. & Langer, R. Tissue engineering: the design and fabrication of living replacement devices for surgical reconstruction and transplantation. Lancet 354 (Suppl. 1): S32–S34 (1999).

    Google Scholar 

  15. 15

    Qi, H. et al. DNA-directed self-assembly of shape-controlled hydrogels. Nat. Commun. 4, 2275 (2013).

    PubMed  PubMed Central  Google Scholar 

  16. 16

    Todhunter, M.E. et al. Programmed synthesis of three-dimensional tissues. Nat. Methods 12, 975–981 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  17. 17

    Cohen, D.L., Malone, E., Lipson, H. & Bonassar, L.J. Direct freeform fabrication of seeded hydrogels in arbitrary geometries. Tissue Eng. 12, 1325–1335 (2006).

    CAS  PubMed  Google Scholar 

  18. 18

    Khalil, S., Nam, J. & Sun, W. Multi-nozzle deposition for construction of 3d biopolymer tissue scaffolds. Rapid Prototyping J. 11, 9–17 (2005).

    Google Scholar 

  19. 19

    Miller, J.S. et al. Rapid casting of patterned vascular networks for perfusable engineered three-dimensional tissues. Nat. Mater. 11, 768–774 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  20. 20

    Kolesky, D.B. et al. 3D bioprinting of vascularized, heterogeneous cell-laden tissue constructs. Adv. Mater. 26, 3124–3130 (2014).

    CAS  PubMed  Google Scholar 

  21. 21

    Murphy, S.V. & Atala, A. 3D bioprinting of tissues and organs. Nat. Biotechnol. 32, 773–785 (2014).

    CAS  PubMed  Google Scholar 

  22. 22

    Colosi, C. et al. Microfluidic bioprinting of heterogeneous 3D tissue constructs using low-viscosity bioink. Adv. Mater. 28, 677–684 (2016).

    CAS  PubMed  Google Scholar 

  23. 23

    Ober, T.J., Foresti, D. & Lewis, J.A. Active mixing of complex fluids at the microscale. Proc. Natl. Acad. Sci. USA 112, 12293–12298 (2015).

    CAS  PubMed  Google Scholar 

  24. 24

    Kang, H.-W. et al. A 3D bioprinting system to produce human-scale tissue constructs with structural integrity. Nat. Biotechnol. 34, 312–319 (2016).

    CAS  PubMed  Google Scholar 

  25. 25

    Karp, J.M. & Leng Teo, G.S. Mesenchymal stem cell homing: the devil is in the details. Cell Stem Cell 4, 206–216 (2009).

    CAS  PubMed  Google Scholar 

  26. 26

    Ranganath, S.H., Levy, O., Inamdar, M.S. & Karp, J.M. Harnessing the mesenchymal stem cell secretome for the treatment of cardiovascular disease. Cell Stem Cell 10, 244–258 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  27. 27

    Sarkar, D. et al. Engineered cell homing. Blood 118, e184–e191 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  28. 28

    Levy, O. et al. mRNA-engineered mesenchymal stem cells for targeted delivery of interleukin-10 to sites of inflammation. Blood 122, e23–e32 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  29. 29

    Zuk, P.A. et al. Human adipose tissue is a source of multipotent stem cells. Mol. Biol. Cell 13, 4279–4295 (2002).

    CAS  PubMed  PubMed Central  Google Scholar 

  30. 30

    De Coppi, P. et al. Isolation of amniotic stem cell lines with potential for therapy. Nat. Biotechnol. 25, 100–106 (2007).

    CAS  Google Scholar 

  31. 31

    Jinek, M. et al. A programmable dual-RNA-guided DNA endonuclease in adaptive bacterial immunity. Science 337, 816–821 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  32. 32

    Cong, L. et al. Multiplex genome engineering using CRISPR/Cas systems. Science 339, 819–823 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  33. 33

    Ran, F.A. et al. Genome engineering using the CRISPR-Cas9 system. Nat. Protoc. 8, 2281–2308 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  34. 34

    Wang, H. et al. One-step generation of mice carrying mutations in multiple genes by CRISPR/Cas-mediated genome engineering. Cell 153, 910–918 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  35. 35

    Servick, K. Gene-editing method revives hopes for transplanting pig organs into people. Science 10.1126/science.aad4700 (2015).

  36. 36

    Reardon, S. New life for pig-to-human transplants. Nature 527, 152–154 (2015).

    CAS  PubMed  Google Scholar 

  37. 37

    Reardon, S. Gene-editing record smashed in pigs. Nature 10.1038/nature.2015.18525 (2015).

  38. 38

    Azagarsamy, M.A. & Anseth, K.S. Bioorthogonal click chemistry: An indispensable tool to create multifaceted cell culture scaffolds. ACS Macro Lett. 2, 5–9 (2013).

    CAS  PubMed  Google Scholar 

  39. 39

    Sakiyama-Elbert, S.E. & Hubbell, J.A. Controlled release of nerve growth factor from a heparin-containing fibrin-based cell ingrowth matrix. J. Control. Release 69, 149–158 (2000).

    CAS  PubMed  Google Scholar 

  40. 40

    Sakiyama-Elbert, S.E. & Hubbell, J.A. Development of fibrin derivatives for controlled release of heparin-binding growth factors. J. Control. Release 65, 389–402 (2000).

    CAS  PubMed  Google Scholar 

  41. 41

    Swift, J. et al. Nuclear lamin-A scales with tissue stiffness and enhances matrix-directed differentiation. Science 341, 1240104 (2013).

    PubMed  PubMed Central  Google Scholar 

  42. 42

    Huebsch, N. et al. Harnessing traction-mediated manipulation of the cell/matrix interface to control stem-cell fate. Nat. Mater. 9, 518–526 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  43. 43

    Khetan, S. et al. Degradation-mediated cellular traction directs stem cell fate in covalently crosslinked three-dimensional hydrogels. Nat. Mater. 12, 458–465 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  44. 44

    Yang, C., Tibbitt, M.W., Basta, L. & Anseth, K.S. Mechanical memory and dosing influence stem cell fate. Nat. Mater. 13, 645–652 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  45. 45

    Anderson, J.M., Rodriguez, A. & Chang, D.T. Foreign body reaction to biomaterials. Semin. Immunol. 20, 86–100 (2008).

    CAS  PubMed  Google Scholar 

  46. 46

    Williams, D.F. On the mechanisms of biocompatibility. Biomaterials 29, 2941–2953 (2008).

    CAS  PubMed  Google Scholar 

  47. 47

    Mantovani, A. et al. The chemokine system in diverse forms of macrophage activation and polarization. Trends Immunol. 25, 677–686 (2004).

    CAS  PubMed  PubMed Central  Google Scholar 

  48. 48

    Porcheray, F. et al. Macrophage activation switching: an asset for the resolution of inflammation. Clin. Exp. Immunol. 142, 481–489 (2005).

    CAS  PubMed  PubMed Central  Google Scholar 

  49. 49

    Fishman, J.M. et al. Immunomodulatory effect of a decellularized skeletal muscle scaffold in a discordant xenotransplantation model. Proc. Natl. Acad. Sci. USA 110, 14360–14365 (2013).

    CAS  PubMed  Google Scholar 

  50. 50

    Spiller, K.L. et al. The role of macrophage phenotype in vascularization of tissue engineering scaffolds. Biomaterials 35, 4477–4488 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  51. 51

    Spiller, K.L. et al. Sequential delivery of immunomodulatory cytokines to facilitate the M1-to-M2 transition of macrophages and enhance vascularization of bone scaffolds. Biomaterials 37, 194–207 (2015).

    CAS  PubMed  Google Scholar 

  52. 52

    Brown, B.N., Ratner, B.D., Goodman, S.B., Amar, S. & Badylak, S.F. Macrophage polarization: an opportunity for improved outcomes in biomaterials and regenerative medicine. Biomaterials 33, 3792–3802 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  53. 53

    Mokarram, N. & Bellamkonda, R.V. A perspective on immunomodulation and tissue repair. Ann. Biomed. Eng. 42, 338–351 (2014).

    PubMed  Google Scholar 

  54. 54

    Du, Y., Lo, E., Ali, S. & Khademhosseini, A. Directed assembly of cell-laden microgels for fabrication of 3D tissue constructs. Proc. Natl. Acad. Sci. USA 105, 9522–9527 (2008).

    CAS  PubMed  Google Scholar 

  55. 55

    Du, Y. et al. Surface-directed assembly of cell-laden microgels. Biotechnol. Bioeng. 105, 655–662 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  56. 56

    Ke, Y., Ong, L.L., Shih, W.M. & Yin, P. Three-dimensional structures self-assembled from DNA bricks. Science 338, 1177–1183 (2012).

    CAS  PubMed  Google Scholar 

  57. 57

    Wei, B., Dai, M. & Yin, P. Complex shapes self-assembled from single-stranded DNA tiles. Nature 485, 623–626 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  58. 58

    Park, A., Wu, B. & Griffith, L.G. Integration of surface modification and 3D fabrication techniques to prepare patterned poly(L-lactide) substrates allowing regionally selective cell adhesion. J. Biomater. Sci. Polym. Ed. 9, 89–110 (1998).

    CAS  PubMed  Google Scholar 

  59. 59

    Giordano, R.A. et al. Mechanical properties of dense polylactic acid structures fabricated by three dimensional printing. J. Biomater. Sci. Polym. Ed. 8, 63–75 (1996).

    CAS  PubMed  Google Scholar 

  60. 60

    Vozzi, G., Flaim, C., Ahluwalia, A. & Bhatia, S. Fabrication of PLGA scaffolds using soft lithography and microsyringe deposition. Biomaterials 24, 2533–2540 (2003).

    CAS  PubMed  Google Scholar 

  61. 61

    Wilson, W.C. Jr. & Boland, T. Cell and organ printing 1: protein and cell printers. Anat. Rec. A Discov. Mol. Cell. Evol. Biol. 272, 491–496 (2003).

    PubMed  Google Scholar 

  62. 62

    Boland, T., Mironov, V., Gutowska, A., Roth, E.A. & Markwald, R.R. Cell and organ printing 2: fusion of cell aggregates in three-dimensional gels. Anat. Rec. A Discov. Mol. Cell. Evol. Biol. 272, 497–502 (2003).

    PubMed  Google Scholar 

  63. 63

    Malda, J. et al. 25th anniversary article: Engineering hydrogels for biofabrication. Adv. Mater. 25, 5011–5028 (2013).

    CAS  PubMed  Google Scholar 

  64. 64

    Bertassoni, L.E. et al. Hydrogel bioprinted microchannel networks for vascularization of tissue engineering constructs. Lab Chip 14, 2202–2211 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  65. 65

    Lee, V.K. et al. Creating perfused functional vascular channels using 3D bio-printing technology. Biomaterials 35, 8092–8102 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  66. 66

    Kolesky, D.B., Homan, K.A., Skylar-Scott, M.A. & Lewis, J.A. Three-dimensional bioprinting of thick vascularized tissues. Proc. Natl. Acad. Sci. USA 113, 3179–3184 (2016).

    CAS  PubMed  Google Scholar 

  67. 67

    Bhattacharjee, T. et al. Writing in the granular gel medium. Sci. Adv. 1, e1500655 (2015).

    PubMed  PubMed Central  Google Scholar 

  68. 68

    Christensen, K. et al. Freeform inkjet printing of cellular structures with bifurcations. Biotechnol. Bioeng. 112, 1047–1055 (2015).

    CAS  PubMed  Google Scholar 

  69. 69

    Highley, C.B., Rodell, C.B. & Burdick, J.A. Direct 3d printing of shear-thinning hydrogels into self-healing hydrogels. Adv. Mater. 27, 5075–5079 (2015).

    CAS  PubMed  Google Scholar 

  70. 70

    Shim, J.-H., Lee, J.-S., Kim, J.Y. & Cho, D.-W.Bioprintingof a mechanically enhanced three-dimensional dual cell-laden construct for osteochondral tissue engineering using a multi-head tissue/organ building system.. J. Micromech. Microeng. 22, 085014 (2012).

    Google Scholar 

  71. 71

    Tibbits, S. 4D printing: multi-material shape change. Architectural Design 84, 116–121 (2014).

    Google Scholar 

  72. 72

    Sydney Gladman, A., Matsumoto, E.A., Nuzzo, R.G., Mahadevan, L. & Lewis, J.A. Biomimetic 4D printing. Nat. Mater. 15, 413–418 (2016).

    CAS  PubMed  Google Scholar 

  73. 73

    Badylak, S.F. The extracellular matrix as a scaffold for tissue reconstruction. in Seminars in Cell & Developmental Biology 377–383 (Elsevier, 2002).

  74. 74

    Ott, H.C. et al. Perfusion-decellularized matrix: using nature's platform to engineer a bioartificial heart. Nat. Med. 14, 213–221 (2008).

    CAS  PubMed  Google Scholar 

  75. 75

    Badylak, S.F., Taylor, D. & Uygun, K. Whole-organ tissue engineering: decellularization and recellularization of three-dimensional matrix scaffolds. Annu. Rev. Biomed. Eng. 13, 27–53 (2011).

    CAS  PubMed  Google Scholar 

  76. 76

    Song, J.J. & Ott, H.C. Organ engineering based on decellularized matrix scaffolds. Trends Mol. Med. 17, 424–432 (2011).

    CAS  PubMed  Google Scholar 

  77. 77

    Arenas-Herrera, J.E., Ko, I.K., Atala, A. & Yoo, J.J. Decellularization for whole organ bioengineering. Biomed. Mater. 8, 014106 (2013).

    CAS  PubMed  Google Scholar 

  78. 78

    Kaushal, S. et al. Functional small-diameter neovessels created using endothelial progenitor cells expanded ex vivo. Nat. Med. 7, 1035–1040 (2001).

    CAS  PubMed  PubMed Central  Google Scholar 

  79. 79

    Amiel, G.E. et al. Engineering of blood vessels from acellular collagen matrices coated with human endothelial cells. Tissue Eng. 12, 2355–2365 (2006).

    CAS  PubMed  Google Scholar 

  80. 80

    Zhang, W. et al. Elastomeric free-form blood vessels for interconnecting organs on chip systems. Lab Chip 16, 1579–1586 (2016).

    PubMed  PubMed Central  Google Scholar 

  81. 81

    Lu, T.-Y. et al. Repopulation of decellularized mouse heart with human induced pluripotent stem cell-derived cardiovascular progenitor cells. Nat. Commun. 4, 2307 (2013).

    PubMed  Google Scholar 

  82. 82

    Ott, H.C. et al. Regeneration and orthotopic transplantation of a bioartificial lung. Nat. Med. 16, 927–933 (2010).

    CAS  PubMed  Google Scholar 

  83. 83

    Petersen, T.H. et al. Tissue-engineered lungs for in vivo implantation. Science 329, 538–541 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  84. 84

    Uygun, B.E. et al. Organ reengineering through development of a transplantable recellularized liver graft using decellularized liver matrix. Nat. Med. 16, 814–820 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  85. 85

    Baptista, P.M. et al. The use of whole organ decellularization for the generation of a vascularized liver organoid. Hepatology 53, 604–617 (2011).

    CAS  PubMed  Google Scholar 

  86. 86

    Sullivan, D.C. et al. Decellularization methods of porcine kidneys for whole organ engineering using a high-throughput system. Biomaterials 33, 7756–7764 (2012).

    CAS  PubMed  Google Scholar 

  87. 87

    Song, J.J. et al. Regeneration and experimental orthotopic transplantation of a bioengineered kidney. Nat. Med. 19, 646–651 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  88. 88

    Atala, A., Bauer, S.B., Soker, S., Yoo, J.J. & Retik, A.B. Tissue-engineered autologous bladders for patients needing cystoplasty. Lancet 367, 1241–1246 (2006).

    PubMed  Google Scholar 

  89. 89

    Goh, S.-K. et al. Perfusion-decellularized pancreas as a natural 3D scaffold for pancreatic tissue and whole organ engineering. Biomaterials 34, 6760–6772 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  90. 90

    Teng, Y.D. et al. Functional recovery following traumatic spinal cord injury mediated by a unique polymer scaffold seeded with neural stem cells. Proc. Natl. Acad. Sci. USA 99, 3024–3029 (2002).

    CAS  PubMed  Google Scholar 

  91. 91

    Niklason, L.E. et al. Functional arteries grown in vitro. Science 284, 489–493 (1999).

    CAS  PubMed  Google Scholar 

  92. 92

    Lancaster, M.A. et al. Cerebral organoids model human brain development and microcephaly. Nature 501, 373–379 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  93. 93

    Choi, S.H. et al. A three-dimensional human neural cell culture model of Alzheimer's disease. Nature 515, 274–278 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  94. 94

    Huh, D., Hamilton, G.A. & Ingber, D.E. From 3D cell culture to organs-on-chips. Trends Cell Biol. 21, 745–754 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  95. 95

    Moraes, C., Mehta, G., Lesher-Perez, S.C. & Takayama, S. Organs-on-a-chip: a focus on compartmentalized microdevices. Ann. Biomed. Eng. 40, 1211–1227 (2012).

    PubMed  Google Scholar 

  96. 96

    Wikswo, J.P. The relevance and potential roles of microphysiological systems in biology and medicine. Exp. Biol. Med. 239, 1061–1072 (2014).

    Google Scholar 

  97. 97

    Bhatia, S.N. & Ingber, D.E. Microfluidic organs-on-chips. Nat. Biotechnol. 32, 760–772 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  98. 98

    Bhise, N.S. et al. Organ-on-a-chip platforms for studying drug delivery systems. J. Control. Release 190, 82–93 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  99. 99

    Zhang, Y.S. & Khademhosseini, A. Seeking the right context for evaluating nanomedicine: from tissue models in petri dishes to microfluidic organs-on-a-chip. Nanomedicine (Lond.) 10, 685–688 (2015).

    CAS  Google Scholar 

  100. 100

    Esch, E.W., Bahinski, A. & Huh, D. Organs-on-chips at the frontiers of drug discovery. Nat. Rev. Drug Discov. 14, 248–260 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  101. 101

    Ingber, D.E. Reverse engineering human pathophysiology with organs-on-chips. Cell 164, 1105–1109 (2016).

    CAS  PubMed  Google Scholar 

  102. 102

    Ebrahimkhani, M.R., Neiman, J.A., Raredon, M.S.B., Hughes, D.J. & Griffith, L.G. Bioreactor technologies to support liver function in vitro. Adv. Drug Deliv. Rev. 69-70, 132–157 (2014).

    CAS  PubMed  Google Scholar 

  103. 103

    Huh, D. et al. Acoustically detectable cellular-level lung injury induced by fluid mechanical stresses in microfluidic airway systems. Proc. Natl. Acad. Sci. USA 104, 18886–18891 (2007).

    CAS  PubMed  Google Scholar 

  104. 104

    Huh, D. et al. Reconstituting organ-level lung functions on a chip. Science 328, 1662–1668 (2010).

    CAS  PubMed  Google Scholar 

  105. 105

    Wilmer, M.J. et al. Kidney-on-a-chip technology for drug-induced nephrotoxicity screening. Trends Biotechnol. 34, 156–170 (2016).

    CAS  PubMed  Google Scholar 

  106. 106

    Kim, S., Lee, H., Chung, M. & Jeon, N.L. Engineering of functional, perfusable 3D microvascular networks on a chip. Lab Chip 13, 1489–1500 (2013).

    CAS  PubMed  Google Scholar 

  107. 107

    Kim, H.J., Huh, D., Hamilton, G. & Ingber, D.E. Human gut-on-a-chip inhabited by microbial flora that experiences intestinal peristalsis-like motions and flow. Lab Chip 12, 2165–2174 (2012).

    CAS  PubMed  Google Scholar 

  108. 108

    Torisawa, Y.-S. et al. Bone marrow-on-a-chip replicates hematopoietic niche physiology in vitro. Nat. Methods 11, 663–669 (2014).

    CAS  PubMed  Google Scholar 

  109. 109

    Nawroth, J.C. et al. A tissue-engineered jellyfish with biomimetic propulsion. Nat. Biotechnol. 30, 792–797 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  110. 110

    Shin, S.R. et al. Aligned carbon nanotube-based flexible gel substrates for engineering bio-hybrid tissue actuators. Adv. Funct. Mater. 25, 4486–4495 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  111. 111

    Raman, R. et al. Optogenetic skeletal muscle-powered adaptive biological machines. Proc. Natl. Acad. Sci. USA 113, 3497–3502 (2016).

    CAS  PubMed  Google Scholar 

  112. 112

    Menze, M.A. et al. Metabolic preconditioning of cells with AICAR-riboside: improved cryopreservation and cell-type specific impacts on energetics and proliferation. Cryobiology 61, 79–88 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  113. 113

    Heo, Y.S. et al. “Universal” vitrification of cells by ultra-fast cooling. Technology (Singap. World Sci.) 3, 64–71 (2015).

    Google Scholar 

  114. 114

    Bruinsma, B.G. et al. Supercooling preservation and transplantation of the rat liver. Nat. Protoc. 10, 484–494 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

Download references

Author information



Corresponding authors

Correspondence to Ali Khademhosseini or Robert Langer.

Ethics declarations

Competing interests

R.L. has equity ownership in In Vivo Therapeutics, Humacyte and Sigilon.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Khademhosseini, A., Langer, R. A decade of progress in tissue engineering. Nat Protoc 11, 1775–1781 (2016). https://doi.org/10.1038/nprot.2016.123

Download citation

Further reading


By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.