Skip to main content

Advertisement

SpringerLink
Log in

Prospects for 3D bioprinting of organoids

  • Review
  • Published:
Bio-Design and Manufacturing Aims and scope Submit manuscript

Abstract

Three-dimensional (3D) organoids derived from pluripotent or adult tissue stem cells seem to possess excellent potential for studying development and disease mechanisms alongside having a myriad of applications in regenerative therapies. However, lack of precise architectures and large-scale tissue sizes are some of the key limitations of current organoid technologies. 3D bioprinting of organoids has recently emerged to address some of these impediments. In this review, we discuss 3D bioprinting with respect to the use of bioinks and bioprinting methods and highlight recent studies that have shown success in bioprinting of stem cells and organoids. We also summarize the use of several vascularization strategies for the bioprinted organoids, that are critical for a complex tissue organization. To fully realize the translational applications of organoids in disease modeling and regenerative medicine, these areas in 3D bioprinting need to be appropriately harnessed and channelized.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

(Bioprinted tissue image is reproduced from Lee et al. [62], copyright year 2017, with permission from Dr. Dong-Woo Cho)

Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Bissell MJ, Hall HG, Parry G (1982) How does the extracellular matrix direct gene expression? J Theor Biol 99:31–68. https://doi.org/10.1016/0022-5193(82)90388-5

    Google Scholar 

  2. Clevers H (2016) Modeling development and disease with organoids. Cell 165:1586–1597. https://doi.org/10.1016/j.cell.2016.05.082

    Google Scholar 

  3. Yoshiki S, Mototsugu E, Hidetaka S (2012) In vitro organogenesis in three dimensions: self-organising stem cells. Development 139:4111–4121. https://doi.org/10.1242/dev.079590

    Google Scholar 

  4. Huch M, Koo BM (2015) Modeling mouse and human development using organoid cultures. Development 142:3113–3125. https://doi.org/10.1242/dev.118570

    Google Scholar 

  5. Blouin A, Bolender RP, Weibel ER (1977) Distribution of organelles and membranes between hepatocytes and nonhepatocytes in the rat liver parenchyma. J Cell Biol 72(2):441–455. https://doi.org/10.1083/jcb.72.2.441

    Google Scholar 

  6. Sato T, Vries RG, Snippert HJ, van de Wetering M, Barker N, Stange DE et al (2009) Single Lgr5 stem cells build crypt-villus structures in vitro without a mesenchymal niche. Nature 459:262–265. https://doi.org/10.1038/nature07935

    Google Scholar 

  7. Napolitano AP, Chai P, Dean DM, Morgan JR (2007) Dynamics of the self-assembly of complex cellular aggregates on micromolded nonadhesive hydrogels. Tissue Eng 13:2087. https://doi.org/10.1089/ten.2006.0190

    Google Scholar 

  8. Fan R, Piou M, Darling E, Cormier D, Sun J, Wan J (2016) Bio-printing cell-laden Matrigel-agarose constructs. J Biomater Appl 31(5):684–692. https://doi.org/10.1177/0885328216669238

    Google Scholar 

  9. Pati F, Jang J, Ha DH et al (2014) Printing three-dimensional tissue analogues with decellularized extracellular matrix bioink. Nat Commun 5:3935. https://doi.org/10.1038/ncomms4935

    Google Scholar 

  10. Skardal A, Devarasetty M, Kang HW et al (2015) A hydrogel bioink toolkit for mimicking native tissue biochemical and mechanical properties in bioprinted tissue constructs. Acta Biomater 25:24–34. https://doi.org/10.1016/j.actbio.2015.07.030

    Google Scholar 

  11. Kundu J, Shim JH, Jang J, Kim SW, Cho DW (2015) An additive manufacturing-based PCL-alginate-chondrocyte bioprinted scaffold for cartilage tissue engineering. J Tissue Eng Regen Med 9:1286–1297. https://doi.org/10.1002/term.1682

    Google Scholar 

  12. Nishiyama Y, Nakamura M, Henmi C et al (2009) Development of a three-dimensional bioprinter: construction of cell supporting structures using hydrogel and state-of-the-art inkjet technology. J Biomech Eng 131(3):035001. https://doi.org/10.1115/1.3002759

    Google Scholar 

  13. Costantini M, Colosi C, Święszkowski W, Barbetta A (2018) Co-axial wet-spinning in 3D bioprinting: state of the art and future perspective of microfluidic integration. Biofabrication 11(1):012001. https://doi.org/10.1088/1758-5090/aae605

    Google Scholar 

  14. Norotte C, Marga FS, Niklason LE, Forgacs G (2009) Scaffold-free vascular tissue engineering using bioprinting. Biomaterials 30(30):5910–5917. shttps://doi.org/10.1016/j.biomaterials.2009.06.034

    Google Scholar 

  15. Koch L, Gruene M, Unger C, Chichkov B (2013) Laser assisted cell printing. Curr Pharm Biotechnol 14(1):91–97. https://doi.org/10.2174/1389201011314010012

    Google Scholar 

  16. Park HK, Shin M, Kim B, Park JW, Lee H (2018) A visible light-curable yet visible wavelength-transparent resin for stereolithography 3D printing. NPG Asia Mater 10(4):82–89. https://doi.org/10.1038/s41427-018-0021-x

    Article  Google Scholar 

  17. Creff J, Courson R, Mangeat T et al (2019) Fabrication of 3D scaffolds reproducing intestinal epithelium topography by high-resolution 3D stereolithography. Biomaterials 221:119404. https://doi.org/10.1016/j.biomaterials.2019.119404

    Google Scholar 

  18. Sun W, Starly B, Daly AC et al (2020) The bioprinting roadmap. Biofabrication 12(2):022002. https://doi.org/10.1088/1758-5090/ab5158

    Google Scholar 

  19. Gu Q, Tomaskovic-Crook E, Wallace GG, Crook JM (2017) 3D bioprinting human induced pluripotent stem cell constructs for in situ cell proliferation and successive multilineage differentiation. Adv Healthc Mater. https://doi.org/10.1002/adhm.201700175

    Article  Google Scholar 

  20. Nguyen D, Hägg DA, Forsman A et al (2017) Cartilage tissue engineering by the 3D bioprinting of iPS cells in a nanocellulose/alginate bioink. Sci Rep 7:658. https://doi.org/10.1038/s41598-017-00690-y

    Google Scholar 

  21. Koch L, Deiwick A, Franke A et al (2018) Laser bioprinting of human induced pluripotent stem cells-the effect of printing and biomaterials on cell survival, pluripotency, and differentiation. Biofabrication 10(3):035005. https://doi.org/10.1088/1758-5090/aab981

    Google Scholar 

  22. Sorkio A, Koch L, Koivusalo L et al (2018) Human stem cell based corneal tissue mimicking structures using laser-assisted 3D bioprinting and functional bioinks. Biomaterials 171:57–71. https://doi.org/10.1016/j.biomaterials.2018.04.034

    Google Scholar 

  23. Yu C, Ma X, Zhu W et al (2019) Scanningless and continuous 3D bioprinting of human tissues with decellularized extracellular matrix. Biomaterials 194:1–13. https://doi.org/10.1016/j.biomaterials.2018.12.009

    Google Scholar 

  24. Ma X, Qu X, Zhu W et al (2016) Deterministically patterned biomimetic human iPSC-derived hepatic model via rapid 3D bioprinting. Proc Natl Acad Sci USA 113(8):2206–2211. https://doi.org/10.1073/pnas.1524510113

    Google Scholar 

  25. Topfer E, Pasotti A, Telopoulou A et al (2019) Bovine colon organoids: from 3D bioprinting to cryopreserved multi-well screening platforms. Toxicol In Vitro 61:104606. https://doi.org/10.1016/j.tiv.2019.104606

    Google Scholar 

  26. Yang H, Sun L, Pang Y et al (2020) Three-dimensional bioprinted hepatorganoids prolong survival of mice with liver failure. Gut:gutjnl 319960. https://doi.org/10.1136/gutjnl-2019-319960

  27. Faulkner-Jones A, Fyfe C, Cornelissen DJ et al (2015) Bioprinting of human pluripotent stem cells and their directed differentiation into hepatocyte-like cells for the generation of mini-livers in 3D. Biofabrication 7(4):044102. https://doi.org/10.1088/1758-5090/7/4/044102

    Google Scholar 

  28. Kupfer ME, Lin WH, Ravikumar V et al (2020) In situ expansion, differentiation, and electromechanical coupling of human cardiac muscle in a 3D bioprinted. Chambered Organoid Circ Res 127(2):207–224. https://doi.org/10.1161/CIRCRESAHA.119.316155

    Google Scholar 

  29. Yap KK, Gerrand YW, Dingle AM, Yeoh GC, Morrison WA, Mitchell GM (2020) Liver sinusoidal endothelial cells promote the differentiation and survival of mouse vascularised hepatobiliary organoids. Biomaterials 251:120091. https://doi.org/10.1016/j.biomaterials.2020.120091

    Google Scholar 

  30. Pleniceanu O, Harari-Steinberg O, Omer D et al (2020) Successful introduction of human renovascular units into the mammalian kidney. J Am Soc Nephrol 31(12):2757–2772. https://doi.org/10.1681/ASN.2019050508

    Article  Google Scholar 

  31. Silvestri VL, Henriet E, Linville RM, Wong AD, Searson PC, Ewald AJ (2020) A tissue-engineered 3D microvessel model reveals the dynamics of mosaic vessel formation in breast cancer. Cancer Res 80(19):4288–4301. https://doi.org/10.1158/0008-5472.CAN-19-1564

    Google Scholar 

  32. Kaushik G, Gupta K, Harms V et al (2020) Engineered perineural vascular plexus for modeling developmental toxicity. Adv Healthc Mater 9(16):e2000825. https://doi.org/10.1002/adhm.202000825

    Google Scholar 

  33. Nzou G, Wicks RT, VanOstrand NR et al (2020) Multicellular 3D neurovascular unit model for assessing hypoxia and neuroinflammation induced blood-brain barrier dysfunction. Sci Rep 10(1):9766. https://doi.org/10.1038/s41598-020-66487-8

    Google Scholar 

  34. Logan S, Arzua T, Yan Y et al (2020) Dynamic characterization of structural, molecular, and electrophysiological phenotypes of human-induced pluripotent stem cell-derived cerebral organoids, and comparison with fetal and adult gene profiles. Cells 9(5):1301. https://doi.org/10.3390/cells9051301

    Google Scholar 

  35. Wimmer RA, Leopoldi A, Aichinger M, Kerjaschki D, Penninger JM (2019) Generation of blood vessel organoids from human pluripotent stem cells. Nat Protoc 14(11):3082–3100. https://doi.org/10.1038/s41596-019-0213-z

    Google Scholar 

  36. Markou M, Kouroupis D, Badounas F et al (2020) Tissue engineering using vascular organoids from human pluripotent stem cell derived mural cell phenotypes. Front Bioeng Biotechnol 8:278. https://doi.org/10.3389/fbioe.2020.00278

    Google Scholar 

  37. Gungor-Ozkerim PS, Inci I, Zhang YS, Khademhosseini A, Dokmeci MR (2018) Bioinks for 3D bioprinting: an overview. Biomater Sci 6(5):915–946. https://doi.org/10.1039/c7bm00765e

    Google Scholar 

  38. Sasmal P, Datta P, Wu Y, Ozbolat IT (2018) 3D bioprinting for modelling vasculature. Microphysiol Syst 2:9. https://doi.org/10.21037/mps.2018.10.02

    Google Scholar 

  39. Rossen NS, Anandakumaran PN, Zur Nieden R et al (2020) Injectable therapeutic organoids using sacrificial hydrogels. iScience 23(5):101052. https://doi.org/10.1016/j.isci.2020.101052

    Google Scholar 

  40. Richardson TP, Peters MC, Ennett AB, Mooney DJ (2001) Polymeric system for dual growth factor delivery. Nat Biotechnol 19(11):1029–1034. https://doi.org/10.1038/nbt1101-1029

    Google Scholar 

  41. Zisch AH, Lutolf MP, Hubbell JA (2003) Biopolymeric delivery matrices for angiogenic growth factors. Cardiovasc Pathol 12(6):295–310. https://doi.org/10.1016/s1054-8807(03)00089-9

    Google Scholar 

  42. Golden AP, Tien J (2007) Fabrication of microfluidic hydrogels using molded gelatin as a sacrificial element. Lab Chip 7(6):720–725. https://doi.org/10.1039/b618409j

    Google Scholar 

  43. King SM, Higgins JW, Nino CR et al (2017) 3D proximal tubule tissues recapitulate key aspects of renal physiology to enable nephrotoxicity testing. Front Physiol 8:123. https://doi.org/10.3389/fphys.2017.00123

    Google Scholar 

  44. Visconti RP, Kasyanov V, Gentile C, Zhang J, Markwald RR, Mironov V (2010) Towards organ printing: engineering an intra-organ branched vascular tree. Expert Opin Biol Ther 10(3):409–420. https://doi.org/10.1517/14712590903563352

    Google Scholar 

  45. Nashimoto Y, Hayashi T, Kunita I et al (2017) Integrating perfusable vascular networks with a three-dimensional tissue in a microfluidic device. Integr Biol (Camb) 9(6):506–518. https://doi.org/10.1039/c7ib00024c

    Google Scholar 

  46. Bartfeld S, Bayram T, van de Wetering M et al (2015) In vitro expansion of human gastric epithelial stem cells and their responses to bacterial infection. Gastroenterology 148(1):126-136.e6. https://doi.org/10.1053/j.gastro.2014.09.042

    Google Scholar 

  47. Huch M, Gehart H, van Boxtel R et al (2015) Long-term culture of genome-stable bipotent stem cells from adult human liver. Cell 160(1–2):299–312. https://doi.org/10.1016/j.cell.2014.11.050

    Google Scholar 

  48. Messina A, Luce E, Hussein M, Dubart-Kupperschmitt A (2020) Pluripotent-stem-cell-derived hepatic cells: hepatocytes and organoids for liver therapy and regeneration. Cells 9(2):420. https://doi.org/10.3390/cells9020420

    Google Scholar 

  49. Hirsch T, Rothoeft T, Teig N et al (2017) Regeneration of the entire human epidermis using transgenic stem cells. Nature 551(7680):327–332. https://doi.org/10.1038/nature24487

    Google Scholar 

  50. Hiller T, Berg J, Elomaa L et al (2018) Generation of a 3D liver model comprising human extracellular matrix in an alginate/gelatin-based bioink by extrusion bioprinting for infection and transduction studies. Int J Mol Sci 19(10):3129. https://doi.org/10.3390/ijms19103129

    Google Scholar 

  51. Park JY, Shim JH, Choi SA, Jang J, Kim M, Lee SH et al (2015) 3D printing technology to control BMP-2 and VEGF delivery spatially and temporally to promote large-volume bone regeneration. J Mater Chem B 3(27):5415–5425. https://doi.org/10.1039/c5tb00637f

    Google Scholar 

  52. Raof NA, Schiele NR, Xie Y, Chrisey DB, Corr DT (2011) The maintenance of pluripotency following laser direct-write of mouse embryonic stem cells. Biomaterials 32(7):1802–1808. https://doi.org/10.1016/j.biomaterials.2010.11.015

    Google Scholar 

  53. Caiazzo M, Okawa Y, Ranga A, Piersigilli A, Tabata Y, Lutolf MP (2016) Defined three-dimensional microenvironments boost induction of pluripotency. Nat Mater 15(3):344–352. https://doi.org/10.1038/nmat4536

    Google Scholar 

  54. Gjorevski N, Sachs N, Manfrin A, Giger S, Bragina ME, Ordóñez-Morán P et al (2016) Designer matrices for intestinal stem cell and organoid culture. Nature 539(7630):560–564. https://doi.org/10.1038/nature20168

    Google Scholar 

  55. Kolesky DB, Truby RL, Gladman AS, Busbee TA, Homan KA, Lewis JA (2014) 3D bioprinting of vascularized, heterogeneous cell-laden tissue constructs. Adv Mater 26(19):3124–3130. https://doi.org/10.1002/adma.201305506

    Google Scholar 

  56. Muller M, Ozturk E, Arlov O, Gatenholm P, Zenobi-Wong M (2017) Alginate sulfate-nanocellulose bioinks for cartilage bioprinting applications. Ann Biomed Eng 45(1):210–223. https://doi.org/10.1007/s10439-016-1704-5

    Google Scholar 

  57. Worthington KS, Wiley LA, Guymon CA, Salem AK, Tucker BA (2016) Differentiation of induced pluripotent stem cells to neural retinal precursor cells on porous poly-lactic-co-glycolic acid scaffolds. J Ocul Pharmacol Ther 32(5):310–316. https://doi.org/10.1089/jop.2015.0126

    Google Scholar 

  58. Zaky SH, Lee KW, Gao J, Jensen A, Close J, Wang Y et al (2014) Poly(glycerol sebacate) elastomer: a novel material for mechanically loaded bone regeneration. Tissue Eng Part A 20(1–2):45–53. https://doi.org/10.1089/ten.TEA.2013.0172

    Google Scholar 

  59. Cho AN, Jin Y, Kim S, Kumar S, Shin H, Kang HC et al (2019) Aligned brain extracellular matrix promotes differentiation and myelination of human-induced pluripotent stem cell-derived oligodendrocytes. ACS Appl Mater Interfaces 11:15344–15353. https://doi.org/10.1021/acsami.9b03242

    Google Scholar 

  60. Catros S, Guillotin B, Bačáaková M, Fricain JC, Guillemot F (2011) Effect of laser energy, substrate film thickness and bioink viscosity on viability of endothelial cells printed by laser-assisted bioprinting. Appl Surf Sci 257:5142–5147. https://doi.org/10.1016/j.apsusc.2010.11.049

    Google Scholar 

  61. Gruene M, Pflaum M, Deiwick A, Koch L, Schlie S, Unger C et al (2011) Adipogenic differentiation of laser-printed 3D tissue grafts consisting of human adipose-derived stem cells. Biofabrication 3(1):015005. https://doi.org/10.1088/1758-5082/3/1/015005

    Google Scholar 

  62. Lee H, Han W, Kim H, Ha DH, Jang J, Kim BS, Cho DW (2017) Development of liver decellularized extracellular matrix bioink for three-dimensional cell printing based liver tissue engineering. Biomacromol 18(4):1229–1237. https://doi.org/10.1021/acs.biomac.6b01908

    Google Scholar 

Download references

Funding

The manuscript was supported by the Department of Science and Technology (DST), India, DST-ASEAN Grant (CRD/2019/000120). The figures have been created with BioRender.com.

Author information

Authors and Affiliations

  1. Department of Molecular and Cellular Medicine, Institute of Liver and Biliary Sciences (ILBS), D1, Vasant Kunj, New Delhi, 110070, India

    Preety Rawal, Dinesh M. Tripathi & Savneet Kaur

  2. School of Biotechnology, Gautam Buddha University, Greater Noida, India

    Preety Rawal

  3. Department of Mechanical Engineering, National University of Singapore, Singapore, Singapore

    Seeram Ramakrishna

Authors
  1. Preety Rawal
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Dinesh M. Tripathi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Seeram Ramakrishna
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Savneet Kaur
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

SK and DMT were involved in conceptualization of the study. PR wrote the manuscript and designed the figures. DMT supervised the figure designing. SR and SK reviewed and edited the final draft. All authors approved the manuscript.

Corresponding author

Correspondence to Savneet Kaur.

Ethics declarations

Conflict of interest

The authors declare no conflict of interests.

Ethical approval

This study does not contain any studies with human or animal subjects performed by any of the authors.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Rawal, P., Tripathi, D.M., Ramakrishna, S. et al. Prospects for 3D bioprinting of organoids. Bio-des. Manuf. 4, 627–640 (2021). https://doi.org/10.1007/s42242-020-00124-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s42242-020-00124-1

Keywords

Search

Navigation