Skip to main content
Log in

Current advances in three-dimensional tissue/organ printing

  • Special Issue–Review Article
  • Published:
Tissue Engineering and Regenerative Medicine Aims and scope

Abstract

Three-dimensional (3D) tissue/organ printing is a major aspect of recent innovation in the field of tissue engineering and regenerative medicine. 3D tissue/organ printing aims to create 3D living tissue/organ analogues, and have evolved along with advances in 3D printing techniques. A diverse range of computer-aided 3D printing techniques have been applied to dispose living cells together with biomaterials and supporting biochemical factors within pre-designed 3D tissue/organ analogues. Recent developments in printable biomaterials, such as decellularized extracellular matrix bio-inks have enabled improvements in the functionality of the resulting 3D tissue/organ analogues. Here, we provide an overview of the 3D printing techniques and biomaterials that have been used, including the development of 3D tissue/organ analogues. In addition, in vitro models are described, and future perspectives in 3D tissue/organ printing are identified.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Sohn YS, Jung JW, Kim JY, Cho DW. Investigation of bi-pore scaffold based on the cell behaviors on 3D scaffold patterns. Tissue Eng Regen Med 2011;8:66–72.

    Google Scholar 

  2. Lee JS, Cha HD, Shim JH, Jung JW, Kim JY, Cho DW. Effect of pore architecture and stacking direction on mechanical properties of solid freeform fabrication-based scaffold for bone tissue engineering. J Biomed Mater Res A 2012;100:1846–1853.

    Article  PubMed  Google Scholar 

  3. Kang HW, Cho DW. Development of an indirect stereolithography technology for scaffold fabrication with a wide range of biomaterial selectivity. Tissue Eng Part C Methods 2012;18:719–729.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Park JH, Jung JW, Kang HW, Joo YH, Lee JS, Cho DW. Development of a 3D bellows tracheal graft: mechanical behavior analysis, fabrication and an in vivo feasibility study. Biofabrication 2012;4:035004.

    Article  PubMed  Google Scholar 

  5. Jung JW, Park JH, Hong JM, Kang HW, Cho DW. Octahedron pore architecture to enhance flexibility of nasal implant-shaped scaffold for rhinoplasty. Int J Precis Eng Manuf 2014;15:2611–2616.

    Article  Google Scholar 

  6. Park JH, Hong JM, Ju YM, Jung JW, Kang HW, Lee SJ, et al. A novel tissue-engineered trachea with a mechanical behavior similar to native trachea. Biomaterials 2015;62:106–115.

    Article  CAS  PubMed  Google Scholar 

  7. Kang HW, Park JH, Kang TY, Seol YJ, Cho DW. Unit cell-based computer-aided manufacturing system for tissue engineering. Biofabrication 2012;4:015005.

    Article  PubMed  Google Scholar 

  8. Hutmacher DW, Sittinger M, Risbud MV. Scaffold-based tissue engineering: rationale for computer-aided design and solid free-form fabrication systems. Trends Biotechnol 2004;22:354–362.

    Article  CAS  PubMed  Google Scholar 

  9. Seol YJ, Kang TY, Cho DW. Solid freeform fabrication technology applied to tissue engineering with various biomaterials. Soft Matter 2012;8:1730–1735.

    Article  CAS  Google Scholar 

  10. Park JH, Jang J, Cho DW. Three-dimensional printed 3D structure for tissue engineering. Trans Korean Soc Mech Eng B 2014;38:817–829.

    Article  Google Scholar 

  11. Mironov V, Reis N, Derby B. Review: bioprinting: a beginning. Tissue Eng 2006;12:631–634.

    Article  PubMed  Google Scholar 

  12. Billiet T, Vandenhaute M, Schelfhout J, Van Vlierberghe S, Dubruel P. A review of trends and limitations in hydrogel-rapid prototyping for tissue engineering. Biomaterials 2012;33:6020–6041.

    Article  CAS  PubMed  Google Scholar 

  13. Derby B. Printing and prototyping of tissues and scaffolds. Science 2012;338:921–926.

    Article  CAS  PubMed  Google Scholar 

  14. Seol YJ, Kang HW, Lee SJ, Atala A, Yoo JJ. Bioprinting technology and its applications. Eur J Cardiothorac Surg 2014;46:342–348.

    Article  PubMed  Google Scholar 

  15. Murphy SV, Atala A. 3D bioprinting of tissues and organs. Nat Biotechnol 2014;32:773–785.

    Article  CAS  PubMed  Google Scholar 

  16. Pati F, Jang J, Ha DH, Kim SW, Rhie JW, Shim JH, et al. Printing three-dimensional tissue analogues with decellularized extracellular matrix bioink. Nat Commun 2014;5:3935.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Pati F, Ha DH, Jang J, Han HH, Rhie JW, Cho DW. Biomimetic 3D tissue printing for soft tissue regeneration. Biomaterials 2015;62:164–175.

    Article  CAS  PubMed  Google Scholar 

  18. Smith CM, Christian JJ, Warren WL, Williams SK. Characterizing environmental factors that impact the viability of tissue-engineered constructs fabricated by a direct-write bioassembly tool. Tissue Eng 2007;13:373–383.

    Article  CAS  PubMed  Google Scholar 

  19. Billiet T, Gevaert E, De Schryver T, Cornelissen M, Dubruel P. The 3D printing of gelatin methacrylamide cell-laden tissue-engineered constructs with high cell viability. Biomaterials 2014;35:49–62.

    Article  CAS  PubMed  Google Scholar 

  20. Hoque ME, Chuan YL, Pashby I. Extrusion based rapid prototyping technique: an advanced platform for tissue engineering scaffold fabrication. Biopolymers 2012;97:83–93.

    Article  CAS  PubMed  Google Scholar 

  21. Shim JH, Kim JY, Park JK, Hahn SK, Rhie JW, Kang SW, et al. Effect of thermal degradation of SFF-based PLGA scaffolds fabricated using a multi-head deposition system followed by change of cell growth rate. J Biomater Sci Polym Ed 2010;21:1069–1080.

    Article  CAS  PubMed  Google Scholar 

  22. Leong KF, Cheah CM, Chua CK. Solid freeform fabrication of three-dimensional scaffolds for engineering replacement tissues and organs. Biomaterials 2003;24:2363–2378.

    Article  CAS  PubMed  Google Scholar 

  23. Kim JY, Park EK, Kim SY, Shin JW, Cho DW. Fabrication of a SFF-based three-dimensional scaffold using a precision deposition system in tissue engineering. J Micromech Microeng 2008;18:055027.

    Article  Google Scholar 

  24. Shim JH, Lee JS, Kim JY, Cho DW. 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 2012;22:085014.

    Article  Google Scholar 

  25. Khalil S, Nam J, Sun W. Multi-nozzle deposition for construction of 3D biopolymer tissue scaffolds. Rapid Prototyp J 2005;11:9–17.

    Article  Google Scholar 

  26. Chang CC, Boland ED, Williams SK, Hoying JB. Direct-write bioprinting three-dimensional biohybrid systems for future regenerative therapies. J Biomed Mater Res B Appl Biomater 2011;98:160–170.

    Article  PubMed  PubMed Central  Google Scholar 

  27. Barry RA, Shepherd RF, Hanson JN, Nuzzo RG, Wiltzius P, Lewis JA. Direct-write assembly of 3D hydrogel scaffolds for guided cell growth. Adv Mater 2009;21:2407–2410.

    Article  CAS  Google Scholar 

  28. Seidi A, Ramalingam M, Elloumi-Hannachi I, Ostrovidov S, Khademhosseini A. Gradient biomaterials for soft-to-hard interface tissue engineering. Acta Biomater 2011;7:1441–1451.

    Article  CAS  PubMed  Google Scholar 

  29. Boland T, Xu T, Damon B, Cui X. Application of inkjet printing to tissue engineering. Biotechnol J 2006;1:910–917.

    Article  CAS  PubMed  Google Scholar 

  30. Le HP. Progress and trends in ink-jet printing technology. J Imaging Sci Technol 1998;42:49–62.

    CAS  Google Scholar 

  31. Odde DJ, Renn MJ. Laser-guided direct writing for applications in biotechnology. Trends Biotechnol 1999;17:385–389.

    Article  CAS  PubMed  Google Scholar 

  32. Lee W, Debasitis JC, Lee VK, Lee JH, Fischer K, Edminster K, et al. Multi-layered culture of human skin fibroblasts and keratinocytes through three-dimensional freeform fabrication. Biomaterials 2009;30:1587–1595.

    Article  CAS  PubMed  Google Scholar 

  33. Nahmias Y, Schwartz RE, Verfaillie CM, Odde DJ. Laser-guided direct writing for three-dimensional tissue engineering. Biotechnol Bioeng 2005;92:129–136.

    Article  CAS  PubMed  Google Scholar 

  34. de Gans BJ, Schubert US. Inkjet printing of well-defined polymer dots and arrays. Langmuir 2004;20:7789–7793.

    Article  CAS  PubMed  Google Scholar 

  35. Melchels FP, Feijen J, Grijpma DW. A review on stereolithography and its applications in biomedical engineering. Biomaterials 2010;31:6121–6130.

    Article  CAS  PubMed  Google Scholar 

  36. Joo YH, Park JH, Cho DW, Sun DI. Morphologic assessment of polycaprolactone scaffolds for tracheal transplantation in a rabbit model. Tissue Eng Regen Med 2013;10:65–70.

    Article  CAS  Google Scholar 

  37. Lu Y, Mapili G, Suhali G, Chen S, Roy K. A digital micro-mirror device-based system for the microfabrication of complex, spatially patterned tissue engineering scaffolds. J Biomed Mater Res A 2006;77:396–405.

    Article  PubMed  Google Scholar 

  38. Dhariwala B, Hunt E, Boland T. Rapid prototyping of tissue-engineering constructs, using photopolymerizable hydrogels and stereolithography. Tissue Eng 2004;10:1316–1322.

    Article  CAS  PubMed  Google Scholar 

  39. Arcaute K, Mann BK, Wicker RB. Stereolithography of three-dimensional bioactive poly(ethylene glycol) constructs with encapsulated cells. Ann Biomed Eng 2006;34:1429–1441.

    Article  PubMed  Google Scholar 

  40. Norotte C, Marga FS, Niklason LE, Forgacs G. Scaffold-free vascular tissue engineering using bioprinting. Biomaterials 2009;30:5910–5917.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Song BR, Yang SS, Jin H, Lee SH, Park DY, Lee JH, et al. Three dimensional plotted extracellular matrix scaffolds using a rapid prototyping for tissue engineering application. Tissue Eng Regen Med 2015;12:172–180.

    Article  CAS  Google Scholar 

  42. Malda J, Visser J, Melchels FP, Jüngst T, Hennink WE, Dhert WJ, et al. 25th anniversary article: engineering hydrogels for biofabrication. Adv Mater 2013;25:5011–5028.

    Article  CAS  PubMed  Google Scholar 

  43. Guillotin B, Guillemot F. Cell patterning technologies for organotypic tissue fabrication. Trends Biotechnol 2011;29:183–190.

    Article  CAS  PubMed  Google Scholar 

  44. Macario DK, Entersz I, Abboud JP, Nackman GB. Inhibition of apoptosis prevents shear-induced detachment of endothelial cells. J Surg Res 2008;147:282–289.

    Article  CAS  PubMed  Google Scholar 

  45. Liu Tsang V, Chen AA, Cho LM, Jadin KD, Sah RL, DeLong S, et al. Fabrication of 3D hepatic tissues by additive photopatterning of cellular hydrogels. FASEB J 2007;21:790–801.

    Article  PubMed  Google Scholar 

  46. Pescosolido L, Schuurman W, Malda J, Matricardi P, Alhaique F, Coviello T, et al. Hyaluronic acid and dextran-based semi-IPN hydrogels as biomaterials for bioprinting. Biomacromolecules 2011;12:1831–1838.

    Article  CAS  PubMed  Google Scholar 

  47. Zhang S. Fabrication of novel biomaterials through molecular self-assembly. Nat Biotechnol 2003;21:1171–1178.

    Article  CAS  PubMed  Google Scholar 

  48. Lee SH, Jo AR, Choi GP, Woo CH, Lee SJ, Kim BS, et al. Fabrication of 3D alginate scaffold with interconnected pores using wire-network molding technique. Tissue Eng Regen Med 2013;10:53–59.

    Article  CAS  Google Scholar 

  49. Park KE, Kim YY, Ku SY, Baek SM, Huh Y, Kim YJ, et al. Effects of alginate hydrogels on in vitro maturation outcome of mouse preantral follicles. Tissue Eng Regen Med 2012;9:170–174.

    Article  CAS  Google Scholar 

  50. Domm C, Schünke M, Christesen K, Kurz B. Redifferentiation of dedifferentiated bovine articular chondrocytes in alginate culture under low oxygen tension. Osteoarthritis Cartilage 2002;10:13–22.

    Article  CAS  PubMed  Google Scholar 

  51. Wei Y, Zeng W, Wan R, Wang J, Zhou Q, Qiu S, et al. Chondrogenic differentiation of induced pluripotent stem cells from osteoarthritic chondrocytes in alginate matrix. Eur Cell Mater 2012;23:1–12.

    Article  CAS  PubMed  Google Scholar 

  52. Laurienzo P, Malinconico M, Motta A, Vicinanza A. Synthesis and characterization of a novel alginate-poly(ethylene glycol) graft copolymer. Carbohydr Polym 2005;62:274–282.

    Article  CAS  Google Scholar 

  53. Lee SH, Chung HY, Shin HI, Park DJ, Choi JH. Osteogenic activity of chitosan-based hybrid scaffold prepared by polyelectrolyte complex formation with alginate. Tissue Eng Regen Med 2014;11:106–112.

    Article  CAS  Google Scholar 

  54. Hong JK, Yun J, Kim H, Kwon SM. Three-dimensional culture of mesenchymal stem cells. Tissue Eng Regen Med 2015;12:211–221.

    Article  CAS  Google Scholar 

  55. Fedorovich NE, Alblas J, de Wijn JR, Hennink WE, Verbout AJ, Dhert WJ. Hydrogels as extracellular matrices for skeletal tissue engineering: state-of-the-art and novel application in organ printing. Tissue Eng 2007;13:1905–1925.

    Article  CAS  PubMed  Google Scholar 

  56. Kim S, Kim BS. Control of adult stem cell behavior with biomaterials. Tissue Eng Regen Med 2014;11:423–430.

    Article  CAS  Google Scholar 

  57. Shim JH, Kim JY, Park M, Park J, Cho DW. Development of a hybrid scaffold with synthetic biomaterials and hydrogel using solid freeform fabrication technology. Biofabrication 2011;3:034102.

    Article  PubMed  Google Scholar 

  58. Ikada Y, Tabata Y. Protein release from gelatin matrices. Adv Drug Deliv Rev 1998;31:287–301.

    Article  PubMed  Google Scholar 

  59. Lee KY, Mooney DJ. Hydrogels for tissue engineering. Chem Rev 2001;101:1869–1879.

    Article  CAS  PubMed  Google Scholar 

  60. Schuurman W, Levett PA, Pot MW, van Weeren PR, Dhert WJ, Hutmacher DW, et al. Gelatin-methacrylamide hydrogels as potential biomaterials for fabrication of tissue-engineered cartilage constructs. Macromol Biosci 2013;13:551–561.

    Article  CAS  PubMed  Google Scholar 

  61. Rutz AL, Hyland KE, Jakus AE, Burghardt WR, Shah RN. A multimaterial bioink method for 3D printing tunable, cell-compatible hydrogels. Adv Mater 2015;27:1607–1614.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Yan Y, Wang X, Xiong Z, Liu H, Liu F, Lin F, et al. Direct construction of a three-dimensional structure with cells and hydrogel. J bioact compat polym 2005;20:259–269.

    Article  CAS  Google Scholar 

  63. Xu W, Wang X, Yan Y, Zheng W, Xiong Z, Lin F, et al. Rapid prototyping three-dimensional cell/gelatin/fibrinogen constructs for medical regeneration. J bioact compat polym 2007;22:363–377.

    Article  CAS  Google Scholar 

  64. Zhao H, Ma L, Zhou J, Mao Z, Gao C, Shen J. Fabrication and physical and biological properties of fibrin gel derived from human plasma. Biomed Mater 2008;3:015001.

    Article  PubMed  Google Scholar 

  65. Spotnitz WD. Commercial fibrin sealants in surgical care. Am J Surg 2001;182(2 Suppl):8S–14S.

    Article  CAS  PubMed  Google Scholar 

  66. Xiong Q, Hill KL, Li Q, Suntharalingam P, Mansoor A, Wang X, et al. A fibrin patch-based enhanced delivery of human embryonic stem cell-derived vascular cell transplantation in a porcine model of postinfarction left ventricular remodeling. Stem Cells 2011;29:367–375.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Whelan D, Caplice NM, Clover AJ. Fibrin as a delivery system in wound healing tissue engineering applications. J Control Release 2014;196:1–8.

    Article  CAS  PubMed  Google Scholar 

  68. Stabenfeldt SE, Gourley M, Krishnan L, Hoying JB, Barker TH. Engineering fibrin polymers through engagement of alternative polymerization mechanisms. Biomaterials 2012;33:535–544.

    Article  CAS  PubMed  Google Scholar 

  69. Hinton TJ, Jallerat Q, Palchesko RN, Park JH, Grodzicki MS, Shue HJ, et al. Three-dimensional printing of complex biological structures by freeform reversible embedding of suspended hydrogels. Sci Adv 2015;1:e1500758.

    Article  Google Scholar 

  70. Gerecht S, Burdick JA, Ferreira LS, Townsend SA, Langer R, Vunjak-Novakovic G. Hyaluronic acid hydrogel for controlled self-renewal and differentiation of human embryonic stem cells. Proc Natl Acad Sci U S A 2007;104:11298–11303.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Collins MN, Birkinshaw C. Hyaluronic acid based scaffolds for tissue engineering—a review. Carbohydr Polym 2013;92:1262–1279.

    Article  CAS  PubMed  Google Scholar 

  72. Kim DH, Martin JT, Elliott DM, Smith LJ, Mauck RL. Phenotypic stability, matrix elaboration and functional maturation of nucleus pulposus cells encapsulated in photocrosslinkable hyaluronic acid hydrogels. Acta Biomater 2015;12:21–29.

    Article  CAS  PubMed  Google Scholar 

  73. Singh S, Afara IO, Tehrani AH, Oloyede A. Effect of decellularization on the load-bearing characteristics of articular cartilage matrix. Tissue Eng Regen Med 2015;12:294–305.

    Article  CAS  Google Scholar 

  74. Chae SY, Chun SY, Park M, Jang YJ, Kim JR, Oh SH, et al. Development of renal extracellular matrix (ECM) scaffold for kidney regeneration. Tissue Eng Regen Med 2014;11:1–7.

    Article  CAS  Google Scholar 

  75. Nguyen MM, Gianneschi NC, Christman KL. Developing injectable nanomaterials to repair the heart. Curr Opin Biotechnol 2015;34:225–231.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Seif-Naraghi SB, Singelyn JM, Salvatore MA, Osborn KG, Wang JJ, Sampat U, et al. Safety and efficacy of an injectable extracellular matrix hydrogel for treating myocardial infarction. Sci Transl Med 2013;5:173ra25.

    Article  Google Scholar 

  77. Kundu J, Shim JH, Jang J, Kim SW, Cho DW. An additive manufacturing-based PCL-alginate-chondrocyte bioprinted scaffold for cartilage tissue engineering. J Tissue Eng Regen Med 2015;9:1286–1297.

    Article  CAS  PubMed  Google Scholar 

  78. Lee JS, Hong JM, Jung JW, Shim JH, Oh JH, Cho DW. 3D printing of composite tissue with complex shape applied to ear regeneration. Bio-fabrication 2014;6:024103.

    PubMed  Google Scholar 

  79. Park JY, Shim JH, Choi SA, Jang J, Kim M, Lee SH, et al. 3D printing technology to control BMP-2 and VEGF delivery spatially and temporally to promote large-volume bone regeneration. J Mater Chem B 2015;3:5415–5425.

    Article  CAS  Google Scholar 

  80. Das S, Pati F, Choi YJ, Rijal G, Shim JH, Kim SW, et al. Bioprintable, cell-laden silk fibroin-gelatin hydrogel supporting multilineage differentiation of stem cells for fabrication of three-dimensional tissue constructs. Acta Biomater 2015;11:233–246.

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  82. Zhao Y, Yao R, Ouyang L, Ding H, Zhang T, Zhang K, et al. Three-dimensional printing of Hela cells for cervical tumor model in vitro. Biofabrication 2014;6:035001.

    Article  PubMed  Google Scholar 

  83. Benam KH, Dauth S, Hassell B, Herland A, Jain A, Jang KJ, et al. Engineered in vitro disease models. Annu Rev Pathol 2015;10:195–262.

    Article  CAS  PubMed  Google Scholar 

  84. Seok J, Warren HS, Cuenca AG, Mindrinos MN, Baker HV, Xu W, et al. Genomic responses in mouse models poorly mimic human inflammatory diseases. Proc Natl Acad Sci U S A 2013;110:3507–3512.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Kimlin L, Kassis J, Virador V. 3D in vitro tissue models and their potential for drug screening. Expert Opin Drug Discov 2013;8:1455–1466.

    Article  CAS  PubMed  Google Scholar 

  86. Griffith LG, Swartz MA. Capturing complex 3D tissue physiology in vitro. Nat Rev Mol Cell Biol 2006;7:211–224.

    Article  CAS  PubMed  Google Scholar 

  87. Szot CS, Buchanan CF, Freeman JW, Rylander MN. 3D in vitro bioengineered tumors based on collagen I hydrogels. Biomaterials 2011;32:7905–7912.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Elliott NT, Yuan F. A review of three-dimensional in vitro tissue models for drug discovery and transport studies. J Pharm Sci 2011;100:59–74.

    Article  CAS  PubMed  Google Scholar 

  89. Chwalek K, Tang-Schomer MD, Omenetto FG, Kaplan DL. In vitro bioengineered model of cortical brain tissue. Nat Protoc 2015;10:1362–1373.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Baptista PM, Siddiqui MM, Lozier G, Rodriguez SR, Atala A, Soker S. The use of whole organ decellularization for the generation of a vascularized liver organoid. Hepatology 2011;53:604–617.

    Article  CAS  PubMed  Google Scholar 

  91. Song HH, Park KM, Gerecht S. Hydrogels to model 3D in vitro microenvironment of tumor vascularization. Adv Drug Deliv Rev 2014;79–80:19–29.

    Article  PubMed  Google Scholar 

  92. Vaidya M. Startups tout commercially 3D-printed tissue for drug screening. Nat Med 2015;21:2.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Dong-Woo Cho.

Additional information

These authors contributed equally to this work.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Park, J.H., Jang, J., Lee, JS. et al. Current advances in three-dimensional tissue/organ printing. Tissue Eng Regen Med 13, 612–621 (2016). https://doi.org/10.1007/s13770-016-8111-8

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13770-016-8111-8

Key Words

Navigation