Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Perspective
  • Published:

Opportunities and challenges of translational 3D bioprinting

Abstract

3D-printed orthopaedic devices and surgical tools, printed maxillofacial implants and other printed acellular devices have been used in patients. By contrast, bioprinted living cellular constructs face considerable translational challenges. In this Perspective, we first summarize the most recent developments in 3D bioprinting for clinical applications, with a focus on how 3D-printed cartilage, bone and skin can be designed for individual patients and fabricated using the patient’s own cells. We then discuss key translational considerations, such as the need to ensure close integration of the living device with the patient’s vascular network, the development of biocompatible bioinks and the challenges in deriving a physiologically relevant number of cells. Lastly, we outline untested regulatory pathways, as well as logistical challenges in material sourcing, manufacturing, standardization and transportation.

This is a preview of subscription content, access via your institution

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: Bioprinted cartilage, bone and skin tissues.
Fig. 2: 3D bioprinting of biomaterials with graded properties.
Fig. 3: Overcoming diffusion limitations and the need for vascularization.

Similar content being viewed by others

References

  1. Tack, P., Victor, J., Gemmel, P. & Annemans, L. 3D-printing techniques in a medical setting: a systematic literature review. Biomed. Eng. Online 15, 115 (2016).

    PubMed  PubMed Central  Google Scholar 

  2. Di Prima, M., Coburn, J., Hwang, D., Kelly, J., Khairuzzaman, A. & Ricles, L. Additively manufactured medical products–the FDA perspective. 3D Print. Med. 2, 1 (2016).

    PubMed  PubMed Central  Google Scholar 

  3. Ventola, C. L. Medical applications for 3D printing: current and projected uses. Pharma. Ther. 39, 704–711 (2014).

    Google Scholar 

  4. Ma, L. et al. 3D printed personalized titanium plates improve clinical outcome in microwave ablation of bone tumors around the knee. Sci. Rep. 7, 7626 (2017).

    PubMed  PubMed Central  Google Scholar 

  5. Li, B. et al. Application of a novel three-dimensional printing genioplasty template system and its clinical validation: a control study. Sci. Rep. 7, 5431 (2017).

    PubMed  PubMed Central  Google Scholar 

  6. Zopf, D. A., Hollister, S. J., Nelson, M. E., Ohye, R. G. & Green, G. E. Bioresorbable airway splint created with a three-dimensional printer. New Eng. J. Med. 368, 2043–2045 (2013).

    CAS  PubMed  Google Scholar 

  7. Morrison, R. J. et al. Mitigation of tracheobronchomalacia with 3D-printed personalized medical devices in pediatric patients. Sci. Transl. Med. 7, 285–264 (2015).

    Google Scholar 

  8. Highlights of Prescribing Information—Spritam 2015 (FDA, 2017).

  9. Mankin, H. J., Mow, V. C., Buckwalter, J. A., Iannotti, J. P. & Ratcliffe, A. Articular cartilage structure, composition, and function. Orthopaed. Basic Sci. 2, 443–470 (2000).

    Google Scholar 

  10. Buckwalter, J. & Mankin, H. Articular cartilage: tissue design and chondrocyte-matrix interactions. Instr. Course Lect. 47, 477–486 (1998).

    CAS  PubMed  Google Scholar 

  11. Hunziker, E., Quinn, T. & Häuselmann, H.-J. Quantitative structural organization of normal adult human articular cartilage. Osteoarth. Cart. 10, 564–572 (2002).

    CAS  Google Scholar 

  12. Sharma, B. et al. Designing zonal organization into tissue-engineered cartilage. Tissue Eng. 13, 405–414 (2007).

    CAS  PubMed  Google Scholar 

  13. Kesti, M. et al. Bioprinting complex cartilaginous structures with clinically compliant biomaterials. Adv. Funct. Mat. 25, 7406–7417 (2015).

    Google Scholar 

  14. Schuurman, W. et al. Gelatin‐methacrylamide hydrogels as potential biomaterials for fabrication of tissue‐engineered cartilage constructs. Macromol. Biosci. 13, 551–561 (2013).

    CAS  PubMed  Google Scholar 

  15. Ávila, H. M., Schwarz, S., Rotter, N. & Gatenholm, P. 3D bioprinting of human chondrocyte-laden nanocellulose hydrogels for patient-specific auricular cartilage regeneration. Bioprinting 1, 22–35 (2016).

    Google Scholar 

  16. Markstedt, K. et al. 3D bioprinting human chondrocytes with nanocellulose–alginate bioink for cartilage tissue engineering applications. Biomacromolecules 16, 1489–1496 (2015).

    CAS  PubMed  Google Scholar 

  17. Hwang, N. S. et al. Response of zonal chondrocytes to extracellular matrix‐hydrogels. FEBS Lett. 581, 4172–4178 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  18. Coates, E. & Fisher, J. P. Gene expression of alginate‐embedded chondrocyte subpopulations and their response to exogenous IGF‐1 delivery. J. Tissue Eng. Regen. Med. 6, 179–192 (2012).

    CAS  PubMed  Google Scholar 

  19. Cui, X., Breitenkamp, K., Finn, M. G., Lotz, M. & D’Lima, D. D. Direct human cartilage repair using three-dimensional bioprinting technology. Tissue Eng. 18, 1304–1312 (2012).

    CAS  Google Scholar 

  20. Gao, G. et al. Improved properties of bone and cartilage tissue from 3D inkjet-bioprinted human mesenchymal stem cells by simultaneous deposition and photocrosslinking in PEG-GelMA. Biotechnol. Lett. 37, 2349 (2015).

    CAS  PubMed  Google Scholar 

  21. Yu, Y. et al. Three-dimensional bioprinting using self-assembling scalable scaffold-free “tissue strands” as a new bioink. Sci. Rep. 6, 28714 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  22. Levato, R. et al. The bio in the ink: cartilage regeneration with bioprintable hydrogels and articular cartilage-derived progenitor cells. Acta Biomater. 61, 41–53 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  23. Nguyen, L. H., Kudva, A. K., Saxena, N. S. & Roy, K. Engineering articular cartilage with spatially-varying matrix composition and mechanical properties from a single stem cell population using a multi-layered hydrogel. Biomaterials 32, 6946–6952 (2011).

    CAS  PubMed  Google Scholar 

  24. Nguyen, L. H., Kudva, A. K., Guckert, N. L., Linse, K. D. & Roy, K. Unique biomaterial compositions direct bone marrow stem cells into specific chondrocytic phenotypes corresponding to the various zones of articular cartilage. Biomaterials 32, 1327–1338 (2011).

    CAS  PubMed  Google Scholar 

  25. Nguyen, D. et al. Cartilage tissue engineering by the 3D bioprinting of iPS cells in a nanocellulose/alginate bioink. Sci. Rep. 7, 658 (2017).

    PubMed  PubMed Central  Google Scholar 

  26. 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 

  27. Gao, M. et al. Tissue-engineered trachea from a 3D-printed scaffold enhances whole-segment tracheal repair. Sci. Rep. 7, 5246 (2017).

    PubMed  PubMed Central  Google Scholar 

  28. Barbero, A. et al. Age related changes in human articular chondrocyte yield, proliferation and post-expansion chondrogenic capacity. Osteoarth. Cartil. 12, 476–484 (2004).

    Google Scholar 

  29. Huang, A. H., Stein, A., Tuan, R. S. & Mauck, R. L. Transient exposure to transforming growth factor beta 3 improves the mechanical properties of mesenchymal stem cell–laden cartilage constructs in a density-dependent manner. Tissue Eng. 15, 3461–3472 (2009).

    CAS  Google Scholar 

  30. Majumdar, M. K., Banks, V., Peluso, D. P. & Morris, E. A. Isolation, characterization, and chondrogenic potential of human bone marrow‐derived multipotential stromal cells. J. Cell. Phys. 185, 98–106 (2000).

    CAS  Google Scholar 

  31. Huang, A. H., Farrell, M. J., Kim, M. & Mauck, R. L. Long-term dynamic loading improves the mechanical properties of chondrogenic mesenchymal stem cell-laden hydrogels. Eur. Cell. Mat. 19, 72 (2010).

    CAS  Google Scholar 

  32. Shegarfi, H. & Reikeras, O. Bone transplantation and immune response. J. Orthopaed. Surg. 17, 206–211 (2009).

    Google Scholar 

  33. Henkel, J. et al. Bone regeneration based on tissue engineering conceptions—a 21st century perspective. Bone Res. 1, 216 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  34. Olszta, M. J. et al. Bone structure and formation: a new perspective. Mat. Sci. Eng. Rep. 58, 77–116 (2007).

    Google Scholar 

  35. Bose, S., Vahabzadeh, S. & Bandyopadhyay, A. Bone tissue engineering using 3D printing. Mat. Today 16, 496–504 (2013).

    CAS  Google Scholar 

  36. Inzana, J. A. et al. 3D printing of composite calcium phosphate and collagen scaffolds for bone regeneration. Biomaterials 35, 4026–4034 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  37. Probst, F., Hutmacher, D., Müller, D., Machens, H. & Schantz, J. Calvarial reconstruction by customized bioactive implant. (German trans.) Handchir. Mikrochir. Plast. Chir. 42, 369–373 (2010).

    CAS  PubMed  Google Scholar 

  38. Catros, S. et al. Laser-assisted bioprinting for creating on-demand patterns of human osteoprogenitor cells and nano-hydroxyapatite. Biofabrication 3, 025001 (2011).

    PubMed  Google Scholar 

  39. Shim, J.-H., Lee, J.-S., Kim, J. Y. & Cho, D.-W. Bioprinting of 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 

  40. Shim, J.-H., Kim, J. Y., Park, M., Park, J. & Cho, D.-W. Development of a hybrid scaffold with synthetic biomaterials and hydrogel using solid freeform fabrication technology. Biofabrication 3, 034102 (2011).

    PubMed  Google Scholar 

  41. Daly, A. C. et al. 3D bioprinting of developmentally inspired templates for whole bone organ engineering. Adv. Health Mater. 5, 2353–2362 (2016).

    CAS  Google Scholar 

  42. Lee, W. et al. Multi-layered culture of human skin fibroblasts and keratinocytes through three-dimensional freeform fabrication. Biomaterials 30, 1587–1595 (2009).

    CAS  PubMed  Google Scholar 

  43. Koch, L. et al. Skin tissue generation by laser cell printing. Biotechnol. Bioeng. 109, 1855–1863 (2012).

    CAS  PubMed  Google Scholar 

  44. Michael, S. et al. Tissue engineered skin substitutes created by laser-assisted bioprinting form skin-like structures in the dorsal skin fold chamber in mice. PLoS ONE 8, e57741 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  45. Lee, W. et al. On‐demand three‐dimensional freeform fabrication of multi‐layered hydrogel scaffold with fluidic channels. Biotechnol. Bioeng. 105, 1178–1186 (2010).

    CAS  PubMed  Google Scholar 

  46. Lee, V. et al. Design and fabrication of human skin by three-dimensional bioprinting. Tissue Eng. Meth. 20, 473–484 (2013).

    Google Scholar 

  47. Cubo, N., Garcia, M., del Cañizo, J. F., Velasco, D. & Jorcano, J. L. 3D bioprinting of functional human skin: production and in vivo analysis. Biofabrication 9, 015006 (2016).

    PubMed  Google Scholar 

  48. Binder, K. W. In situ bioprinting of the skin. PhD thesis, Wake Forest University (2011).

  49. Albanna, M. et al. In situ bioprinting of autologous skin cells accelerates wound healing of extensive excisional full-thickness wounds. Sci. Rep. 9, 1856 (2019).

    PubMed  PubMed Central  Google Scholar 

  50. Skardal, A. et al. Bioprinted amniotic fluid‐derived stem cells accelerate healing of large skin wounds. Stem Cell. Transl. Med. 1, 792–802 (2012).

    CAS  Google Scholar 

  51. Skardal, A. et al. A tunable hydrogel system for long‐term release of cell‐secreted cytokines and bioprinted in situ wound cell delivery. J. Biomed. Mat. Res. Appl. Biomat. 105, 1986–2000 (2017).

    CAS  Google Scholar 

  52. Ito, M. et al. Stem cells in the hair follicle bulge contribute to wound repair but not to homeostasis of the epidermis. Nat. Med. 11, 1351 (2005).

    CAS  PubMed  Google Scholar 

  53. Hsu, Y.-C., Li, L. & Fuchs, E. Emerging interactions between skin stem cells and their niches. Nat. Med. 20, 847–856 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  54. Ahn, G. et al. Precise stacking of decellularized extracellular matrix based 3D cell-laden constructs by a 3D cell printing system equipped with heating modules. Sci. Rep. 7, 8624 (2017).

    PubMed  PubMed Central  Google Scholar 

  55. Murphy, S. V., Skardal, A. & Atala, A. Evaluation of hydrogels for bio‐printing applications. J. Biomed. Mat. Res. 101, 272–284 (2013).

    Google Scholar 

  56. Hardin, J. O., Ober, T. J., Valentine, A. D. & Lewis, J. A. Microfluidic printheads for multimaterial 3D printing of viscoelastic inks. Adv. Mater. 27, 3279–3284 (2015).

    CAS  PubMed  Google Scholar 

  57. 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  PubMed Central  Google Scholar 

  58. Cui, H. et al. Hierarchical fabrication of engineered vascularized bone biphasic constructs via dual 3D bioprinting: integrating regional bioactive factors into architectural design. Adv. Health Mater. 5, 2174–2181 (2016).

    CAS  Google Scholar 

  59. Merceron, T. K. et al. A 3D bioprinted complex structure for engineering the muscle–tendon unit. Biofabrication 7, 035003 (2015).

    PubMed  Google Scholar 

  60. Huang, G. et al. Engineering three-dimensional cell mechanical microenvironment with hydrogels. Biofabrication 4, 042001 (2012).

    PubMed  Google Scholar 

  61. Skardal, A. et al. A hydrogel bioink toolkit for mimicking native tissue biochemical and mechanical properties in bioprinted tissue constructs. Acta Biomater. 25, 24–34 (2015).

    CAS  PubMed  Google Scholar 

  62. Zarembinski, T. I. & Skardal, A. in Hydrogels-Smart Materials for Biomedical Applications (ed. Popa, L.) Ch. 5 (IntechOpen, 2018).

  63. Skardal, A. et al. Photocrosslinkable hyaluronan-gelatin hydrogels for two-step bioprinting. Tissue Eng. 16, 2675 (2010).

    CAS  Google Scholar 

  64. Fan, H. et al. Fabrication, mechanical properties, and biocompatibility of graphene-reinforced chitosan composites. Biomacromolecules 11, 2345–2351 (2010).

    CAS  PubMed  Google Scholar 

  65. Zhang, S. Emerging biological materials through molecular self-assembly. Biotechnol. Adv. 20, 321–339 (2002).

    CAS  PubMed  Google Scholar 

  66. Zhang, S. Fabrication of novel biomaterials through molecular self-assembly. Nat. Biotechnol. 21, 1171–1178 (2003).

    CAS  PubMed  Google Scholar 

  67. Gelain, F., Horii, A. & Zhang, S. Designer self‐assembling peptide scaffolds for 3‐D tissue cell cultures and regenerative medicine. Macromol. Biosci. 7, 544–551 (2007).

    CAS  PubMed  Google Scholar 

  68. Mano, J. F. Stimuli‐responsive polymeric systems for biomedical applications. Adv. Eng. Mat. 10, 515–527 (2008).

    CAS  Google Scholar 

  69. Karbarz, M., Mackiewicz, M., Kaniewska, K., Marcisz, K. & Stojek, Z. Recent developments in design and functionalization of micro-and nanostructural environmentally-sensitive hydrogels based on N-isopropylacrylamide. Appl. Mat. Today 9, 516–532 (2017).

    Google Scholar 

  70. Liu, X. et al. ROCK inhibitor and feeder cells induce the conditional reprogramming of epithelial cells. Am. J. Path. 180, 599–607 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  71. Chapman, S., Liu, X., Meyers, C., Schlegel, R. & McBride, A. A. Human keratinocytes are efficiently immortalized by a Rho kinase inhibitor. J. Clin. Investig. 120, 2619 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  72. Dominici, M. et al. Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy 8, 315–317 (2006).

    CAS  PubMed  Google Scholar 

  73. Pittenger, M. F. et al. Multilineage potential of adult human mesenchymal stem cells. Science 284, 143–147 (1999).

    CAS  PubMed  Google Scholar 

  74. 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 

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

    PubMed  Google Scholar 

  76. Wagner, W. et al. Replicative senescence of mesenchymal stem cells: a continuous and organized process. PLoS ONE 3, e2213 (2008).

    PubMed  PubMed Central  Google Scholar 

  77. Zhou, S. et al. Age‐related intrinsic changes in human bone‐marrow‐derived mesenchymal stem cells and their differentiation to osteoblasts. Aging Cell 7, 335–343 (2008).

    CAS  PubMed  Google Scholar 

  78. Choudhery, M. S., Badowski, M., Muise, A., Pierce, J. & Harris, D. T. Donor age negatively impacts adipose tissue-derived mesenchymal stem cell expansion and differentiation. J. Transl. Med. 12, 8 (2014).

    PubMed  PubMed Central  Google Scholar 

  79. Stolzing, A., Jones, E., McGonagle, D. & Scutt, A. Age-related changes in human bone marrow-derived mesenchymal stem cells: consequences for cell therapies. Mech. Ageing Dev. 129, 163–173 (2008).

    CAS  PubMed  Google Scholar 

  80. Takahashi, K. et al. Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell 131, 861–872 (2007).

    CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  82. Kimbrel, E. A. & Lanza, R. Current status of pluripotent stem cells: moving the first therapies to the clinic. Nat. Rev. Drug Discov. 14, 681–692 (2015).

    CAS  PubMed  Google Scholar 

  83. Scudellari, M. How iPS cells changed the world. Nature 534, 310–312 (2016).

    PubMed  Google Scholar 

  84. Lee, A. S., Tang, C., Rao, M. S., Weissman, I. L. & Wu, J. C. Tumorigenicity as a clinical hurdle for pluripotent stem cell therapies. Nat. Med. 19, 998–1004 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  85. Trounson, A. & DeWitt, N. D. Pluripotent stem cells progressing to the clinic. Nat. Rev. Mol. Cell Biol. 17, 194–200 (2016).

    CAS  PubMed  Google Scholar 

  86. Mandai, M. et al. Autologous induced stem-cell-derived retinal cells for macular degeneration. New Engl. J. Med. 376, 1038–1046 (2017).

    CAS  PubMed  Google Scholar 

  87. Simonson, O. E., Domogatskaya, A., Volchkov, P. & Rodin, S. The safety of human pluripotent stem cells in clinical treatment. Ann. Med. 47, 370–380 (2015).

    PubMed  Google Scholar 

  88. Ma, H. et al. Abnormalities in human pluripotent cells due to reprogramming mechanisms. Nature 511, 177–183 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  89. Okita, K. et al. A more efficient method to generate integration-free human iPS cells. Nat. Methods 8, 409–412 (2011).

    CAS  PubMed  Google Scholar 

  90. Umekage, M., Sato, Y. & Takasu, N. Overview: an iPS cell stock at CiRA. Inflamm. Regen. 39, 17 (2019).

    PubMed  PubMed Central  Google Scholar 

  91. Deegan, D. B., Zimmerman, C., Skardal, A., Atala, A. & Shupe, T. D. Stiffness of hyaluronic acid gels containing liver extracellular matrix supports human hepatocyte function and alters cell morphology. J. Mech. Behav. Biomed. Mater. 55, 87–103 (2016).

    CAS  Google Scholar 

  92. Loneker, A. E., Faulk, D. M., Hussey, G. S., D’Amore, A. & Badylak, S. F. Solubilized liver extracellular matrix maintains primary rat hepatocyte phenotype in‐vitro. J. Biomed. Mat. Res. 104, 957–965 (2016).

    CAS  Google Scholar 

  93. Kobayashi, J., Akiyama, Y., Yamato, M. & Okano, T. ECM-mimicking thermoresponsive surface for manipulating hepatocyte sheets with maintenance of hepatic functions. in 2016 International Symposium on Micro-NanoMechatronics and Human Science (MHS) (IEEE, 2016)

  94. Huch, M. et al. Long-term culture of genome-stable bipotent stem cells from adult human liver. Cell 160, 299–312 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  95. Moroni, L. et al. Biofabrication: a guide to technology and terminology. Trends Biotechnol. 36, 348–402 (2017).

    Google Scholar 

  96. Mironov, V. et al. Organ printing: tissue spheroids as building blocks. Biomaterials 30, 2164–2174 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  97. Jakab, K. et al. Tissue engineering by self-assembly of cells printed into topologically defined structures. Tissue Eng. 14, 413–421 (2008).

    CAS  Google Scholar 

  98. Janssen, F. W., Oostra, J., van Oorschot, A. & van Blitterswijk, C. A. A perfusion bioreactor system capable of producing clinically relevant volumes of tissue-engineered bone: in vivo bone formation showing proof of concept. Biomaterials 27, 315–323 (2006).

    CAS  PubMed  Google Scholar 

  99. Brown, D. A. et al. Analysis of oxygen transport in a diffusion‐limited model of engineered heart tissue. Biotechnol. Bioeng. 97, 962–975 (2007).

    CAS  PubMed  Google Scholar 

  100. Jain, R. K., Au, P., Tam, J., Duda, D. G. & Fukumura, D. Engineering vascularized tissue. Nat. Biotechnol. 23, 821–823 (2005).

    CAS  PubMed  Google Scholar 

  101. Muschler, G. F., Nakamoto, C. & Griffith, L. G. Engineering principles of clinical cell-based tissue engineering. JBJS 86, 1541–1558 (2004).

    Google Scholar 

  102. Bertassoni, L. E. et al. Direct-write bioprinting of cell-laden methacrylated gelatin hydrogels. Biofabrication 6, 024105 (2014).

    PubMed  PubMed Central  Google Scholar 

  103. 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 

  104. Poldervaart, M. T. et al. Prolonged presence of VEGF promotes vascularization in 3D bioprinted scaffolds with defined architecture. J. Contr. Release 184, 58–66 (2014).

    CAS  Google Scholar 

  105. Wu, W., DeConinck, A. & Lewis, J. A. Omnidirectional printing of 3D microvascular networks. Adv. Mater. 23, 178–183 (2011).

    Google Scholar 

  106. Ozbolat, I. T. Bioprinting scale-up tissue and organ constructs for transplantation. Trends Biotechnol. 33, 395–400 (2015).

    CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  108. 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  PubMed Central  Google Scholar 

  109. Norotte, C., Marga, F. S., Niklason, L. E. & Forgacs, G. Scaffold-free vascular tissue engineering using bioprinting. Biomaterials 30, 5910–5917 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  110. Zhu, W. et al. Direct 3D bioprinting of prevascularized tissue constructs with complex microarchitecture. Biomaterials 124, 106–115 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  111. Hansen, C. J. et al. High‐throughput printing via microvascular multinozzle arrays. Adv. Mater. 25, 96–102 (2013).

    CAS  PubMed  Google Scholar 

  112. Traore, M. A. & George, S. C. Tissue Engineering the Vascular Tree. Tissue Eng. Rev. 23, 505–514 (2017).

    CAS  Google Scholar 

  113. Ehsan, S. M. & George, S. C. Nonsteady state oxygen transport in engineered tissue: implications for design. Tissue Eng. 19, 1433–1442 (2013).

    CAS  Google Scholar 

  114. Ehsan, S. M. & George, S. C. Vessel network formation in response to intermittent hypoxia is frequency dependent. J. Biosci. Bioeng. 120, 347–350 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  115. Hsu, Y. H., Moya, M. L., Hughes, C. C., George, S. C. & Lee, A. P. A microfluidic platform for generating large-scale nearly identical human microphysiological vascularized tissue arrays. Lab Chip 13, 2990–2998 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  116. Tumbleston, J. R. et al. Additive manufacturing: continuous liquid interface production of 3D objects. Science 347, 1349–1352 (2015).

    CAS  PubMed  Google Scholar 

  117. Kengla, C. et al. Clinically relevant bioprinting workflow and imaging process for tssue construct design and validation. 3D Print. Addit. Manuf. 4, 239–247 (2017).

    Google Scholar 

  118. Tibbits, S. Design to self-Assembly. Arch. Des. 82, 68–73 (2012).

    Google Scholar 

  119. Bonamici, S. H. R.34 - 21st Century Cures Act Senate Report 114–146 (United States Congress, 2016).

  120. Technical Considerations for Additive Manufactured Medical Devices - Guidance for Industry and Food and Drug Administration Staff (FDA, 2017).

  121. Hunsberger, J. G., Goel, S., Allickson, J. & Atala, A. Five critical areas that combat high costs and prolonged development times for regenerative medicine manufacturing. Curr. Stem Cell Rep. 3, 77–82 (2017).

    Google Scholar 

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

    PubMed  Google Scholar 

  123. Kuribayashi-Shigetomi, K., Onoe, H. & Takeuchi, S. Cell origami: self-folding of three-dimensional cell-laden microstructures driven by cell traction force. PLoS ONE 7, e51085 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

P.D.C. is supported by the National Institute for Health Research (NIHR-RP-2014-04-046) and by the NIHR Great Ormond Street Hospital Biomedical Research Centre.

Author information

Authors and Affiliations

Authors

Contributions

S.V.M, P.D.C and A.A. discussed the content, researched the literature and wrote the manuscript.

Corresponding author

Correspondence to Sean V. Murphy.

Ethics declarations

Competing interests

The authors declare no competing interests.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Murphy, S.V., De Coppi, P. & Atala, A. Opportunities and challenges of translational 3D bioprinting. Nat Biomed Eng 4, 370–380 (2020). https://doi.org/10.1038/s41551-019-0471-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41551-019-0471-7

This article is cited by

Search

Quick links

Nature Briefing: Translational Research

Sign up for the Nature Briefing: Translational Research newsletter — top stories in biotechnology, drug discovery and pharma.

Get what matters in translational research, free to your inbox weekly. Sign up for Nature Briefing: Translational Research