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.

3D bioprinting of tissues and organs

Abstract

Additive manufacturing, otherwise known as three-dimensional (3D) printing, is driving major innovations in many areas, such as engineering, manufacturing, art, education and medicine. Recent advances have enabled 3D printing of biocompatible materials, cells and supporting components into complex 3D functional living tissues. 3D bioprinting is being applied to regenerative medicine to address the need for tissues and organs suitable for transplantation. Compared with non-biological printing, 3D bioprinting involves additional complexities, such as the choice of materials, cell types, growth and differentiation factors, and technical challenges related to the sensitivities of living cells and the construction of tissues. Addressing these complexities requires the integration of technologies from the fields of engineering, biomaterials science, cell biology, physics and medicine. 3D bioprinting has already been used for the generation and transplantation of several tissues, including multilayered skin, bone, vascular grafts, tracheal splints, heart tissue and cartilaginous structures. Other applications include developing high-throughput 3D-bioprinted tissue models for research, drug discovery and toxicology.

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

Figure 1: A typical process for bioprinting 3D tissues.
Figure 2: Components of inkjet, microextrusion and laser-assisted bioprinters.

Katie Vicari/Nature Publishing Group

Figure 3: Examples of human-scale bioprinted tissues.
Figure 4: Timeframe for the development of various types of 3D bioprinted tissues.

References

  1. 1

    Kruth, J.-P. Material incress manufacturing by rapid prototyping techniques. CIRP Annals-Manufacturing Technology 40, 603–614 (1991).

    Google Scholar 

  2. 2

    Hull, C.W. et al. Method of and apparatus for forming a solid three-dimensional article from a liquid medium. WO 1991012120 A1 (Google Patents, 1991).

  3. 3

    Malone, E. & Lipson, H. Fab@ Home: the personal desktop fabricator kit. Rapid Prototyping J. 13, 245–255 (2007).

    Google Scholar 

  4. 4

    Allard, T., Sitchon, M., Sawatzky, R. & Hoppa, R. Use of hand-held laser scanning and 3D printing for creation of a museum exhibit. in 6th International Symposium on Virtual Reality, Archaelogy and Cultural Heritage (2005).

    Google Scholar 

  5. 5

    Shimizu, T.S. et al. Molecular model of a lattice of signalling proteins involved in bacterial chemotaxis. Nat. Cell Biol. 2, 792–796 (2000).

    CAS  PubMed  Google Scholar 

  6. 6

    Bailey, M.J., Schulten, K. & Johnson, J.E. The use of solid physical models for the study of macromolecular assembly. Curr. Opin. Struct. Biol. 8, 202–208 (1998).

    CAS  PubMed  Google Scholar 

  7. 7

    Symes, M.D. et al. Integrated 3D-printed reactionware for chemical synthesis and analysis. Nat. Chem. 4, 349–354 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  8. 8

    Gonzalez-Gomez, J., Valero-Gomez, A., Prieto-Moreno, A. & Abderrahim, M. A new open source 3D-printable mobile robotic platform for education. in Advances in Autonomous Mini Robots 49–62 (Springer, 2012).

    Google Scholar 

  9. 9

    Hull, C.W. Apparatus for production of three-dimensional objects by stereolithography. US 4575330 A (Google Patents, 1986).

  10. 10

    Nakamura, M., Iwanaga, S., Henmi, C., Arai, K. & Nishiyama, Y. Biomatrices and biomaterials for future developments of bioprinting and biofabrication. Biofabrication 2, 014110 (2010).

    CAS  PubMed  Google Scholar 

  11. 11

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

    CAS  PubMed  PubMed Central  Google Scholar 

  12. 12

    Michelson, R.C. Novel approaches to miniature flight platforms. Proc. Inst. Mech. Eng. Part G J. Aerosp. Eng. 218, 363–373 (2004).

    Google Scholar 

  13. 13

    Reed, E.J., Klumb, L., Koobatian, M. & Viney, C. Biomimicry as a route to new materials: what kinds of lessons are useful? Philos Trans A Math Phys. Eng. Sci. 367, 1571–1585 (2009).

    CAS  PubMed  Google Scholar 

  14. 14

    Huh, D., Torisawa, Y.S., Hamilton, G.A., Kim, H.J. & Ingber, D.E. Microengineered physiological biomimicry: organs-on-chips. Lab Chip 12, 2156–2164 (2012).

    CAS  Google Scholar 

  15. 15

    Ingber, D.E. et al. Tissue engineering and developmental biology: going biomimetic. Tissue Eng. 12, 3265–3283 (2006).

    CAS  PubMed  Google Scholar 

  16. 16

    Marga, F., Neagu, A., Kosztin, I. & Forgacs, G. Developmental biology and tissue engineering. Birth Defects Res. C Embryo Today 81, 320–328 (2007).

    CAS  PubMed  Google Scholar 

  17. 17

    Steer, D.L. & Nigam, S.K. Developmental approaches to kidney tissue engineering. Am. J. Physiol. Renal Physiol. 286, F1–F7 (2004).

    CAS  PubMed  Google Scholar 

  18. 18

    Derby, B. Printing and prototyping of tissues and scaffolds. Science 338, 921–926 (2012).

    CAS  Google Scholar 

  19. 19

    Kasza, K.E. et al. The cell as a material. Curr. Opin. Cell Biol. 19, 101–107 (2007).

    CAS  PubMed  Google Scholar 

  20. 20

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

    CAS  PubMed  PubMed Central  Google Scholar 

  21. 21

    Kelm, J.M. et al. A novel concept for scaffold-free vessel tissue engineering: self-assembly of microtissue building blocks. J. Biotechnol. 148, 46–55 (2010).

    CAS  PubMed  Google Scholar 

  22. 22

    Kamei, M. et al. Endothelial tubes assemble from intracellular vacuoles in vivo. Nature 442, 453–456 (2006).

    CAS  PubMed  PubMed Central  Google Scholar 

  23. 23

    Alajati, A. et al. Spheroid-based engineering of a human vasculature in mice. Nat. Methods 5, 439–445 (2008).

    CAS  PubMed  Google Scholar 

  24. 24

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

    CAS  Google Scholar 

  25. 25

    Sonntag, F. et al. Design and prototyping of a chip-based multi-micro-organoid culture system for substance testing, predictive to human (substance) exposure. J. Biotechnol. 148, 70–75 (2010).

    CAS  PubMed  Google Scholar 

  26. 26

    Gunther, A. et al. A microfluidic platform for probing small artery structure and function. Lab Chip 10, 2341–2349 (2010).

    PubMed  PubMed Central  Google Scholar 

  27. 27

    Mankovich, N.J., Samson, D., Pratt, W., Lew, D. & Beumer, J. III. Surgical planning using three-dimensional imaging and computer modeling. Otolaryngol. Clin. North Am. 27, 875–889 (1994).

    CAS  PubMed  Google Scholar 

  28. 28

    Pykett, I.L. et al. Principles of nuclear magnetic resonance imaging. Radiology 143, 157–168 (1982).

    CAS  PubMed  Google Scholar 

  29. 29

    Megibow, A.J. & Bosniak, M.A. Dilute barium as a contrast agent for abdominal CT. AJR Am. J. Roentgenol. 134, 1273–1274 (1980).

    CAS  PubMed  Google Scholar 

  30. 30

    Zagoria, R.J. Iodinated contrast agents in neuroradiology. Neuroimaging Clin. N. Am. 4, 1–8 (1994).

    CAS  PubMed  PubMed Central  Google Scholar 

  31. 31

    Johnson, W.K., Stoupis, C., Torres, G.M., Rosenberg, E.B. & Ros, P.R. Superparamagnetic iron oxide (SPIO) as an oral contrast agent in gastrointestinal (GI) magnetic resonance imaging (MRI): comparison with state-of-the-art computed tomography (CT). Magn. Reson. Imaging 14, 43–49 (1996).

    CAS  PubMed  Google Scholar 

  32. 32

    Wolf, G.L. Current status of MR imaging contrast agents: special report. Radiology 172, 709–710 (1989).

    CAS  PubMed  Google Scholar 

  33. 33

    Matsumoto, Y. & Jasanoff, A. Metalloprotein-based MRI probes. FEBS Lett. 587, 1021–1029 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  34. 34

    Mironov, V. et al. Biofabrication: a 21st century manufacturing paradigm. Biofabrication 1, 022001 (2009).

    CAS  PubMed  Google Scholar 

  35. 35

    Horn, T.J. & Harrysson, O.L. Overview of current additive manufacturing technologies and selected applications. Sci. Prog. 95, 255–282 (2012).

    CAS  PubMed  Google Scholar 

  36. 36

    Sun, W. & Lal, P. Recent development on computer aided tissue engineering–a review. Comput. Methods Programs Biomed. 67, 85–103 (2002).

    PubMed  Google Scholar 

  37. 37

    Hollister, S.J. Porous scaffold design for tissue engineering. Nat. Mater. 4, 518–524 (2005).

    CAS  PubMed  Google Scholar 

  38. 38

    Peltola, S.M., Melchels, F.P., Grijpma, D.W. & Kellomaki, M. A review of rapid prototyping techniques for tissue engineering purposes. Ann. Med. 40, 268–280 (2008).

    CAS  PubMed  Google Scholar 

  39. 39

    Hutmacher, D.W., Sittinger, M. & Risbud, M.V. Scaffold-based tissue engineering: rationale for computer-aided design and solid free-form fabrication systems. Trends Biotechnol. 22, 354–362 (2004).

    CAS  PubMed  Google Scholar 

  40. 40

    Klebe, R.J. Cytoscribing: a method for micropositioning cells and the construction of two- and three-dimensional synthetic tissues. Exp. Cell Res. 179, 362–373 (1988).

    CAS  PubMed  Google Scholar 

  41. 41

    Xu, T. et al. Complex heterogeneous tissue constructs containing multiple cell types prepared by inkjet printing technology. Biomaterials 34, 130–139 (2013).

    PubMed  Google Scholar 

  42. 42

    Xu, T., Jin, J., Gregory, C., Hickman, J.J. & Boland, T. Inkjet printing of viable mammalian cells. Biomaterials 26, 93–99 (2005).

    PubMed  Google Scholar 

  43. 43

    Cui, X., Boland, T., D'Lima, D.D. & Lotz, M.K. Thermal inkjet printing in tissue engineering and regenerative medicine. Recent Pat. Drug Deliv. Formul. 6, 149–155 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  44. 44

    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 

  45. 45

    Iwami, K. et al. Bio rapid prototyping by extruding/aspirating/refilling thermoreversible hydrogel. Biofabrication 2, 014108 (2010).

    CAS  PubMed  Google Scholar 

  46. 46

    Shor, L. et al. Precision extruding deposition (PED) fabrication of polycaprolactone (PCL) scaffolds for bone tissue engineering. Biofabrication 1, 015003 (2009).

    PubMed  Google Scholar 

  47. 47

    Barron, J.A., Wu, P., Ladouceur, H.D. & Ringeisen, B.R. Biological laser printing: a novel technique for creating heterogeneous 3-dimensional cell patterns. Biomed. Microdevices 6, 139–147 (2004).

    CAS  PubMed  Google Scholar 

  48. 48

    Guillemot, F. et al. High-throughput laser printing of cells and biomaterials for tissue engineering. Acta Biomater. 6, 2494–2500 (2010).

    CAS  PubMed  Google Scholar 

  49. 49

    Guillotin, B. et al. Laser assisted bioprinting of engineered tissue with high cell density and microscale organization. Biomaterials 31, 7250–7256 (2010).

    CAS  PubMed  Google Scholar 

  50. 50

    Xu, T., Kincaid, H., Atala, A. & Yoo, J.J. High-throughput production of single-cell microparticles using an inkjet printing technology. J. Manuf. Sci. Eng. 130, 021017–021017 (2008).

    Google Scholar 

  51. 51

    Xu, T. et al. Characterization of cell constructs generated with inkjet printing technology using in vivo magnetic resonance imaging. J. Manuf. Sci. Eng. 130, 021013–021013 (2008).

    Google Scholar 

  52. 52

    Okamoto, T., Suzuki, T. & Yamamoto, N. Microarray fabrication with covalent attachment of DNA using bubble jet technology. Nat. Biotechnol. 18, 438–441 (2000).

    CAS  PubMed  Google Scholar 

  53. 53

    Goldmann, T. & Gonzalez, J.S. DNA-printing: utilization of a standard inkjet printer for the transfer of nucleic acids to solid supports. J. Biochem. Biophys. Methods 42, 105–110 (2000).

    CAS  PubMed  Google Scholar 

  54. 54

    Xu, T. et al. Viability and electrophysiology of neural cell structures generated by the inkjet printing method. Biomaterials 27, 3580–3588 (2006).

    CAS  PubMed  PubMed Central  Google Scholar 

  55. 55

    Cui, X., Dean, D., Ruggeri, Z.M. & Boland, T. Cell damage evaluation of thermal inkjet printed Chinese hamster ovary cells. Biotechnol. Bioeng. 106, 963–969 (2010).

    CAS  PubMed  Google Scholar 

  56. 56

    Tekin, E., Smith, P.J. & Schubert, U.S. Inkjet printing as a deposition and patterning tool for polymers and inorganic particles. Soft Matter 4, 703–713 (2008).

    CAS  Google Scholar 

  57. 57

    Fang, Y. et al. Rapid generation of multiplexed cell cocultures using acoustic droplet ejection followed by aqueous two-phase exclusion patterning. Tissue Eng. Part C Methods 18, 647–657 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  58. 58

    Demirci, U. & Montesano, G. Single cell epitaxy by acoustic picolitre droplets. Lab Chip 7, 1139–1145 (2007).

    CAS  PubMed  Google Scholar 

  59. 59

    Saunders, R., Bosworth, L., Gough, J., Derby, B. & Reis, N. Selective cell delivery for 3D tissue culture and engineering. Eur. Cell. Mater. 7, 84–85 (2004).

    Google Scholar 

  60. 60

    Saunders, R.E., Gough, J.E. & Derby, B. Delivery of human fibroblast cells by piezoelectric drop-on-demand inkjet printing. Biomaterials 29, 193–203 (2008).

    CAS  PubMed  Google Scholar 

  61. 61

    Nakamura, M. et al. Biocompatible inkjet printing technique for designed seeding of individual living cells. Tissue Eng. 11, 1658–1666 (2005).

    CAS  PubMed  Google Scholar 

  62. 62

    Tasoglu, S. & Demirci, U. Bioprinting for stem cell research. Trends Biotechnol. 31, 10–19 (2013).

    CAS  PubMed  Google Scholar 

  63. 63

    Kim, J.D., Choi, J.S., Kim, B.S., Chan Choi, Y. & Cho, Y.W. Piezoelectric inkjet printing of polymers: Stem cell patterning on polymer substrates. Polymer 51, 2147–2154 (2010).

    CAS  Google Scholar 

  64. 64

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

    PubMed  Google Scholar 

  65. 65

    Khalil, S. & Sun, W. Biopolymer deposition for freeform fabrication of hydrogel tissue constructs. Mater. Sci. Eng. C 27, 469–478 (2007).

    CAS  Google Scholar 

  66. 66

    Hennink, W.E. & van Nostrum, C.F. Novel crosslinking methods to design hydrogels. Adv. Drug Deliv. Rev. 54, 13–36 (2002).

    CAS  PubMed  Google Scholar 

  67. 67

    Skardal, A., Zhang, J. & Prestwich, G.D. Bioprinting vessel-like constructs using hyaluronan hydrogels crosslinked with tetrahedral polyethylene glycol tetracrylates. Biomaterials 31, 6173–6181 (2010).

    CAS  PubMed  Google Scholar 

  68. 68

    Campbell, P.G., Miller, E.D., Fisher, G.W., Walker, L.M. & Weiss, L.E. Engineered spatial patterns of FGF-2 immobilized on fibrin direct cell organization. Biomaterials 26, 6762–6770 (2005).

    CAS  PubMed  Google Scholar 

  69. 69

    Phillippi, J.A. et al. Microenvironments engineered by inkjet bioprinting spatially direct adult stem cells toward muscle- and bone-like subpopulations. Stem Cells 26, 127–134 (2008).

    CAS  PubMed  Google Scholar 

  70. 70

    Sekitani, T., Noguchi, Y., Zschieschang, U., Klauk, H. & Someya, T. Organic transistors manufactured using inkjet technology with subfemtoliter accuracy. Proc. Natl. Acad. Sci. USA 105, 4976–4980 (2008).

    CAS  PubMed  Google Scholar 

  71. 71

    Singh, M., Haverinen, H.M., Dhagat, P. & Jabbour, G.E. Inkjet printing-process and its applications. Adv. Mater. 22, 673–685 (2010).

    CAS  PubMed  Google Scholar 

  72. 72

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

    CAS  PubMed  PubMed Central  Google Scholar 

  73. 73

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

    CAS  PubMed  PubMed Central  Google Scholar 

  74. 74

    Xu, T. et al. Hybrid printing of mechanically and biologically improved constructs for cartilage tissue engineering applications. Biofabrication 5, 015001 (2013).

    PubMed  Google Scholar 

  75. 75

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

    CAS  PubMed  Google Scholar 

  76. 76

    Smith, C.M. et al. Three-dimensional bioassembly tool for generating viable tissue-engineered constructs. Tissue Eng. 10, 1566–1576 (2004).

    CAS  PubMed  Google Scholar 

  77. 77

    Jones, N. Science in three dimensions: the print revolution. Nature 487, 22–23 (2012).

    CAS  PubMed  Google Scholar 

  78. 78

    Chang, C.C., Boland, E.D., Williams, S.K. & Hoying, J.B. Direct-write bioprinting three-dimensional biohybrid systems for future regenerative therapies. J. Biomed. Mater. Res. B Appl. Biomater. 98, 160–170 (2011).

    PubMed  PubMed Central  Google Scholar 

  79. 79

    Fedorovich, N.E. et al. Evaluation of photocrosslinked Lutrol hydrogel for tissue printing applications. Biomacromolecules 10, 1689–1696 (2009).

    CAS  PubMed  Google Scholar 

  80. 80

    Chang, R., Nam, J. & Sun, W. Effects of dispensing pressure and nozzle diameter on cell survival from solid freeform fabrication-based direct cell writing. Tissue Eng. Part A 14, 41–48 (2008).

    CAS  PubMed  Google Scholar 

  81. 81

    Jakab, K., Damon, B., Neagu, A., Kachurin, A. & Forgacs, G. Three-dimensional tissue constructs built by bioprinting. Biorheology 43, 509–513 (2006).

    PubMed  Google Scholar 

  82. 82

    Visser, J. et al. Biofabrication of multi-material anatomically shaped tissue constructs. Biofabrication 5, 035007 (2013).

    PubMed  Google Scholar 

  83. 83

    Censi, R. et al. The tissue response to photopolymerized PEG-p(HPMAm-lactate)-based hydrogels. J. Biomed. Mater. Res. A 97, 219–229 (2011).

    PubMed  Google Scholar 

  84. 84

    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 

  85. 85

    Smith, C.M., Christian, J.J., Warren, W.L. & Williams, S.K. Characterizing environmental factors that impact the viability of tissue-engineered constructs fabricated by a direct-write bioassembly tool. Tissue Eng. 13, 373–383 (2007).

    CAS  PubMed  Google Scholar 

  86. 86

    Guvendiren, M., Lu, H.D. & Burdick, J.A. Shear-thinning hydrogels for biomedical applications. Soft Matter 8, 260–272 (2012).

    CAS  Google Scholar 

  87. 87

    Marga, F. et al. Organ printing: a novel tissue engineering paradigm. in 5th European Conference of the International Federation for Medical and Biological Engineering 27–30 (Springer, 2012).

    Google Scholar 

  88. 88

    Mironov, V., Kasyanov, V. & Markwald, R.R. Organ printing: from bioprinter to organ biofabrication line. Curr. Opin. Biotechnol. 22, 667–673 (2011).

    CAS  PubMed  Google Scholar 

  89. 89

    Marga, F. et al. Toward engineering functional organ modules by additive manufacturing. Biofabrication 4, 022001 (2012).

    PubMed  Google Scholar 

  90. 90

    Nair, K. et al. Characterization of cell viability during bioprinting processes. Biotechnol. J. 4, 1168–1177 (2009).

    CAS  PubMed  Google Scholar 

  91. 91

    Skardal, A., Zhang, J., McCoard, L., Oottamasathien, S. & Prestwich, G.D. Dynamically crosslinked gold nanoparticle—hyaluronan hydrogels. Adv. Mater. 22, 4736–4740 (2010).

    CAS  PubMed  Google Scholar 

  92. 92

    Skardal, A. et al. Photocrosslinkable hyaluronan-gelatin hydrogels for two-step bioprinting. Tissue Eng. Part A 16, 2675–2685 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  93. 93

    Duan, B., Hockaday, L.A., Kang, K.H. & Butcher, J.T. 3D bioprinting of heterogeneous aortic valve conduits with alginate/gelatin hydrogels. J. Biomed. Mater. Res. A 101, 1255–1264 (2013).

    PubMed  Google Scholar 

  94. 94

    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 

  95. 95

    Chang, R., Nam, J. & Sun, W. Direct cell writing of 3D microorgan for in vitro pharmacokinetic model. Tissue Eng. Part C Methods 14, 157–166 (2008).

    CAS  PubMed  Google Scholar 

  96. 96

    Xu, F. et al. A three-dimensional in vitro ovarian cancer coculture model using a high-throughput cell patterning platform. Biotechnol. J. 6, 204–212 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  97. 97

    Bohandy, J., Kim, B. & Adrian, F. Metal deposition from a supported metal film using an excimer laser. J. Appl. Phys. 60, 1538–1539 (1986).

    CAS  Google Scholar 

  98. 98

    Barron, J.A., Ringeisen, B.R., Kim, H., Spargo, B.J. & Chrisey, D.B. Application of laser printing to mammalian cells. Thin Solid Films 453, 383–387 (2004).

    Google Scholar 

  99. 99

    Chrisey, D.B. Materials processing: the power of direct writing. Science 289, 879–881 (2000).

    CAS  PubMed  Google Scholar 

  100. 100

    Colina, M., Serra, P., Fernandez-Pradas, J.M., Sevilla, L. & Morenza, J.L. DNA deposition through laser induced forward transfer. Biosens. Bioelectron. 20, 1638–1642 (2005).

    CAS  PubMed  Google Scholar 

  101. 101

    Dinca, V. et al. Directed three-dimensional patterning of self-assembled peptide fibrils. Nano Lett. 8, 538–543 (2008).

    CAS  PubMed  Google Scholar 

  102. 102

    Ringeisen, B.R. et al. Laser printing of pluripotent embryonal carcinoma cells. Tissue Eng. 10, 483–491 (2004).

    CAS  PubMed  Google Scholar 

  103. 103

    Guillemot, F., Souquet, A., Catros, S. & Guillotin, B. Laser-assisted cell printing: principle, physical parameters versus cell fate and perspectives in tissue engineering. Nanomedicine 5, 507–515 (2010).

    PubMed  Google Scholar 

  104. 104

    Hopp, B. et al. Survival and proliferative ability of various living cell types after laser-induced forward transfer. Tissue Eng. 11, 1817–1823 (2005).

    CAS  PubMed  Google Scholar 

  105. 105

    Gruene, M. et al. Laser printing of stem cells for biofabrication of scaffold-free autologous grafts. Tissue Eng. Part C Methods 17, 79–87 (2011).

    PubMed  Google Scholar 

  106. 106

    Koch, L. et al. Laser printing of skin cells and human stem cells. Tissue Eng. Part C Methods 16, 847–854 (2010).

    CAS  PubMed  Google Scholar 

  107. 107

    Guillotin, B. & Guillemot, F. Cell patterning technologies for organotypic tissue fabrication. Trends Biotechnol. 29, 183–190 (2011).

    CAS  PubMed  Google Scholar 

  108. 108

    Kattamis, N.T., Purnick, P.E., Weiss, R. & Arnold, C.B. Thick film laser induced forward transfer for deposition of thermally and mechanically sensitive materials. Appl. Phys. Lett. 91, 171120–171123 (2007).

    Google Scholar 

  109. 109

    Duocastella, M., Fernandez-Pradas, J., Morenza, J., Zafra, D. & Serra, P. Novel laser printing technique for miniaturized biosensors preparation. Sens. Actuators B Chem. 145, 596–600 (2010).

    CAS  Google Scholar 

  110. 110

    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 

  111. 111

    Keriquel, V. et al. In vivo bioprinting for computer- and robotic-assisted medical intervention: preliminary study in mice. Biofabrication 2, 014101 (2010).

    PubMed  Google Scholar 

  112. 112

    Hunt, N.C. & Grover, L.M. Cell encapsulation using biopolymer gels for regenerative medicine. Biotechnol. Lett. 32, 733–742 (2010).

    CAS  PubMed  Google Scholar 

  113. 113

    Sun, J. et al. Chitosan functionalized ionic liquid as a recyclable biopolymer-supported catalyst for cycloaddition of CO2. Green Chem. 14, 654–660 (2012).

    CAS  Google Scholar 

  114. 114

    Spiller, K.L., Maher, S.A. & Lowman, A.M. Hydrogels for the repair of articular cartilage defects. Tissue Eng. Part B Rev. 17, 281–299 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  115. 115

    Li, Z. & Kawashita, M. Current progress in inorganic artificial biomaterials. J. Artif. Organs 14, 163–170 (2011).

    CAS  PubMed  Google Scholar 

  116. 116

    Talbot, E.L., Berson, A., Brown, P.S. & Bain, C.D. Evaporation of picoliter droplets on surfaces with a range of wettabilities and thermal conductivities. Phys. Rev. E 85, 061604 (2012).

    CAS  Google Scholar 

  117. 117

    Hopp, B.L. et al. Femtosecond laser printing of living cells using absorbing film-assisted laser-induced forward transfer. Optical Engineering 51, 014302–014306 (2012).

    Google Scholar 

  118. 118

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

    CAS  Google Scholar 

  119. 119

    West, J.L. & Hubbell, J.A. Polymeric biomaterials with degradation sites for proteases involved in cell migration. Macromolecules 32, 241–244 (1999).

    CAS  Google Scholar 

  120. 120

    Ananthanarayanan, A., Narmada, B.C., Mo, X., McMillian, M. & Yu, H. Purpose-driven biomaterials research in liver-tissue engineering. Trends Biotechnol. 29, 110–118 (2011).

    CAS  PubMed  Google Scholar 

  121. 121

    Hutmacher, D.W. Scaffolds in tissue engineering bone and cartilage. Biomaterials 21, 2529–2543 (2000).

    CAS  PubMed  Google Scholar 

  122. 122

    Limpanuphap, S. & Derby, B. Manufacture of biomaterials by a novel printing process. J. Mater. Sci. Mater. Med. 13, 1163–1166 (2002).

    CAS  PubMed  Google Scholar 

  123. 123

    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 

  124. 124

    Zhang, S. et al. Self-complementary oligopeptide matrices support mammalian cell attachment. Biomaterials 16, 1385–1393 (1995).

    PubMed  Google Scholar 

  125. 125

    Hersel, U., Dahmen, C. & Kessler, H. RGD modified polymers: biomaterials for stimulated cell adhesion and beyond. Biomaterials 24, 4385–4415 (2003).

    CAS  PubMed  Google Scholar 

  126. 126

    Karp, J.M. et al. Controlling size, shape and homogeneity of embryoid bodies using poly(ethylene glycol) microwells. Lab Chip 7, 786–794 (2007).

    CAS  PubMed  Google Scholar 

  127. 127

    Teixeira, A.I., Nealey, P.F. & Murphy, C.J. Responses of human keratocytes to micro- and nanostructured substrates. J. Biomed. Mater. Res. A 71, 369–376 (2004).

    PubMed  Google Scholar 

  128. 128

    Price, R.L., Haberstroh, K.M. & Webster, T.J. Enhanced functions of osteoblasts on nanostructured surfaces of carbon and alumina. Med. Biol. Eng. Comput. 41, 372–375 (2003).

    CAS  PubMed  Google Scholar 

  129. 129

    Behonick, D.J. & Werb, Z. A bit of give and take: the relationship between the extracellular matrix and the developing chondrocyte. Mech. Dev. 120, 1327–1336 (2003).

    CAS  PubMed  PubMed Central  Google Scholar 

  130. 130

    Discher, D.E., Janmey, P. & Wang, Y.L. Tissue cells feel and respond to the stiffness of their substrate. Science 310, 1139–1143 (2005).

    CAS  Google Scholar 

  131. 131

    Stevens, M.M. & George, J.H. Exploring and engineering the cell surface interface. Science 310, 1135–1138 (2005).

    CAS  PubMed  Google Scholar 

  132. 132

    Baptista, P.M. et al. Whole organ decellularization–a tool for bioscaffold fabrication and organ bioengineering. Conf. Proc. IEEE Eng. Med. Biol. Soc. 2009, 6526–6529 (2009).

    PubMed  PubMed Central  Google Scholar 

  133. 133

    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 

  134. 134

    Hynes, R.O. & Naba, A. Overview of the matrisome–an inventory of extracellular matrix constituents and functions. Cold Spring Harb. Perspect. Biol. 4, a004903 (2012).

    PubMed  PubMed Central  Google Scholar 

  135. 135

    Ambesi-Impiombato, F.S., Parks, L.A. & Coon, H.G. Culture of hormone-dependent functional epithelial cells from rat thyroids. Proc. Natl. Acad. Sci. USA 77, 3455–3459 (1980).

    CAS  PubMed  Google Scholar 

  136. 136

    Hamm, A., Krott, N., Breibach, I., Blindt, R. & Bosserhoff, A.K. Efficient transfection method for primary cells. Tissue Eng. 8, 235–245 (2002).

    CAS  PubMed  Google Scholar 

  137. 137

    Okumura, N. et al. Enhancement on primate corneal endothelial cell survival in vitro by a ROCK inhibitor. Invest. Ophthalmol. Vis. Sci. 50, 3680–3687 (2009).

    PubMed  Google Scholar 

  138. 138

    Yu, Z. et al. ROCK inhibition with Y27632 promotes the proliferation and cell cycle progression of cultured astrocyte from spinal cord. Neurochem. Int. 61, 1114–1120 (2012).

    CAS  PubMed  Google Scholar 

  139. 139

    Dimri, G.P. et al. A biomarker that identifies senescent human cells in culture and in aging skin in vivo. Proc. Natl. Acad. Sci. USA 92, 9363–9367 (1995).

    CAS  PubMed  Google Scholar 

  140. 140

    Reubinoff, B.E., Pera, M.F., Fong, C.Y., Trounson, A. & Bongso, A. Embryonic stem cell lines from human blastocysts: somatic differentiation in vitro. Nat. Biotechnol. 18, 399–404 (2000).

    CAS  Google Scholar 

  141. 141

    Friedenstein, A.J. et al. Precursors for fibroblasts in different populations of hematopoietic cells as detected by the in vitro colony assay method. Exp. Hematol. 2, 83–92 (1974).

    CAS  PubMed  PubMed Central  Google Scholar 

  142. 142

    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 

  143. 143

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

    CAS  PubMed  PubMed Central  Google Scholar 

  144. 144

    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 

  145. 145

    Murphy, S. et al. Amnion epithelial cell isolation and characterization for clinical use. Curr. Protoc. Stem Cell Biol. 1E6 (2010).

  146. 146

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

    CAS  Google Scholar 

  147. 147

    Gillette, B.M., Jensen, J.A., Wang, M., Tchao, J. & Sia, S.K. Dynamic hydrogels: switching of 3D microenvironments using two-component naturally derived extracellular matrices. Adv. Mater. 22, 686–691 (2010).

    CAS  PubMed  Google Scholar 

  148. 148

    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 

  149. 149

    Chun, S.Y. et al. Identification and characterization of bioactive factors in bladder submucosa matrix. Biomaterials 28, 4251–4256 (2007).

    CAS  PubMed  Google Scholar 

  150. 150

    Schuurman, W. et al. Bioprinting of hybrid tissue constructs with tailorable mechanical properties. Biofabrication 3, 021001 (2011).

    CAS  PubMed  Google Scholar 

  151. 151

    Ding, S. et al. Synthetic small molecules that control stem cell fate. Proc. Natl. Acad. Sci. USA 100, 7632–7637 (2003).

    CAS  PubMed  Google Scholar 

  152. 152

    Li, X.J. et al. Directed differentiation of ventral spinal progenitors and motor neurons from human embryonic stem cells by small molecules. Stem Cells 26, 886–893 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  153. 153

    Chen, S. et al. A small molecule that directs differentiation of human ESCs into the pancreatic lineage. Nat. Chem. Biol. 5, 258–265 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  154. 154

    Chen, S., Zhang, Q., Wu, X., Schultz, P.G. & Ding, S. Dedifferentiation of lineage-committed cells by a small molecule. J. Am. Chem. Soc. 126, 410–411 (2004).

    CAS  PubMed  Google Scholar 

  155. 155

    Visconti, R.P. et al. Towards organ printing: engineering an intra-organ branched vascular tree. Expert Opin. Biol. Ther. 10, 409–420 (2010).

    PubMed  PubMed Central  Google Scholar 

  156. 156

    Perez-Pomares, J.M. et al. In vitro self-assembly of proepicardial cell aggregates: an embryonic vasculogenic model for vascular tissue engineering. Anat. Rec. A Discov. Mol. Cell. Evol. Biol. 288, 700–713 (2006).

    PubMed  Google Scholar 

  157. 157

    Tan, Q. et al. Accelerated angiogenesis by continuous medium flow with vascular endothelial growth factor inside tissue-engineered trachea. Eur. J. Cardiothorac. Surg. 31, 806–811 (2007).

    PubMed  Google Scholar 

  158. 158

    Harrison, B.S., Eberli, D., Lee, S.J., Atala, A. & Yoo, J.J. Oxygen producing biomaterials for tissue regeneration. Biomaterials 28, 4628–4634 (2007).

    CAS  PubMed  Google Scholar 

  159. 159

    Salehi-Nik, N. et al. Engineering parameters in bioreactor's design: a critical aspect in tissue engineering. Biomed Res. Int. 2013, 762132 (2013).

    PubMed  PubMed Central  Google Scholar 

Download references

Author information

Affiliations

Authors

Corresponding author

Correspondence to Anthony Atala.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Murphy, S., Atala, A. 3D bioprinting of tissues and organs. Nat Biotechnol 32, 773–785 (2014). https://doi.org/10.1038/nbt.2958

Download citation

Further reading

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing