Three-dimensional bioprinting of gelatin methacryloyl (GelMA)

Abstract

The three-dimensional (3D) bioprinting technology has progressed tremendously over the past decade. By controlling the size, shape, and architecture of the bioprinted constructs, 3D bioprinting allows for the fabrication of tissue/organ-like constructs with strong structural–functional similarity with their in vivo counterparts at high fidelity. The bioink, a blend of biomaterials and living cells possessing both high biocompatibility and printability, is a critical component of bioprinting. In particular, gelatin methacryloyl (GelMA) has shown its potential as a viable bioink material due to its suitable biocompatibility and readily tunable physicochemical properties. Current GelMA-based bioinks and relevant bioprinting strategies for GelMA bioprinting are briefly reviewed.

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

Fig. 1
Fig. 2

Reproduced with permission [31]

Fig. 3

Reproduced with permission [33]

Fig. 4

Reproduced with permission [39]

Fig. 5

Reproduced with permission [45]

Fig. 6

Reproduced with permission [49]

References

  1. 1.

    Griffith LG, Naughton G (2002) Tissue engineering–current challenges and expanding opportunities. Science 295:1009–1014

    Article  Google Scholar 

  2. 2.

    Atala A (2009) Engineering organs. Curr Opin Biotech 20:575–592

    Article  Google Scholar 

  3. 3.

    Lanza R, Langer R, Vacanti JP (2011) Principles of tissue engineering. Academic press, Cambridge

    Google Scholar 

  4. 4.

    Langer R (2007) Tissue engineering: perspectives, challenges, and future directions. Tissue Eng 13:1–2

    Article  Google Scholar 

  5. 5.

    Khademhosseini A, Langer R (2016) A decade of progress in tissue engineering. Nat Protoc 11:1775

    Article  Google Scholar 

  6. 6.

    Chaudhari AA, Vig K, Baganizi DR, Sahu R, Dixit S, Dennis V, Singh SR, Pillai SR (1974) Future prospects for scaffolding methods and biomaterials in skin tissue engineering: a review. Int J Mol Sci 2016:17

    Google Scholar 

  7. 7.

    Makris EA, Gomoll AH, Malizos KN, Hu JC, Athanasiou KA (2015) Repair and tissue engineering techniques for articular cartilage. Nat Protoc 11:21

    Google Scholar 

  8. 8.

    Zhang YS, Yue K, Aleman J, Mollazadeh-Moghaddam K, Bakht SM, Yang J, Jia W, Dell’Erba V, Assawes P, Shin SR (2017) 3D bioprinting for tissue and organ fabrication. Ann Biomed Eng 45:148–163

    Article  Google Scholar 

  9. 9.

    Murphy SV, Atala A (2014) 3D bioprinting of tissues and organs. Nat Biotechnol 32:773

    Article  Google Scholar 

  10. 10.

    Jia W, Gungor-Ozkerim PS, Zhang YS, Yue K, Zhu K, Liu W, Pi Q, Byambaa B, Dokmeci MR, Shin SR (2016) Direct 3D bioprinting of perfusable vascular constructs using a blend bioink. Biomaterials 106:58–68

    Article  Google Scholar 

  11. 11.

    Liu W, Zhang YS, Heinrich MA, De Ferrari F, Jang HL, Bakht SM, Alvarez MM, Yang J, Li YC, Trujillo-de Santiago G (2017) Rapid continuous multimaterial extrusion bioprinting. Adv Mater 29:1604630

    Article  Google Scholar 

  12. 12.

    Ozbolat IT, Hospodiuk M (2016) Current advances and future perspectives in extrusion-based bioprinting. Biomaterials 76:321–343

    Article  Google Scholar 

  13. 13.

    Kang H-W, Lee SJ, Ko IK, Kengla C, Yoo JJ, Atala A (2016) A 3D bioprinting system to produce human-scale tissue constructs with structural integrity. Nat Biotechnol 34:312

    Article  Google Scholar 

  14. 14.

    Hölzl K, Lin S, Tytgat L, Van Vlierberghe S, Gu L, Ovsianikov A (2016) Bioink properties before, during and after 3D bioprinting. Biofabrication 8:032002

    Article  Google Scholar 

  15. 15.

    Liu W, Heinrich MA, Zhou Y, Akpek A, Hu N, Liu X, Guan X, Zhong Z, Jin X, Khademhosseini A (2017) Extrusion bioprinting of shear-thinning gelatin methacryloyl bioinks. Adv Healthc Mater 6:1601451

    Article  Google Scholar 

  16. 16.

    Wang Z, Kumar H, Tian Z, Jin X, Holzman JF, Menard F, Kim K (2018) Visible light photoinitiation of cell-adhesive gelatin methacryloyl hydrogels for stereolithography 3D bioprinting. ACS Appl Mater Interfaces 10:26859–26869

    Article  Google Scholar 

  17. 17.

    Klotz BJ, Gawlitta D, Rosenberg AJ, Malda J, Melchels FP (2016) Gelatin-methacryloyl hydrogels: towards biofabrication-based tissue repair. Trends Biotechnol 34:394–407

    Article  Google Scholar 

  18. 18.

    Wu D, Yu Y, Tan J, Huang L, Luo B, Lu L, Zhou C (2018) 3D bioprinting of gellan gum and poly (ethylene glycol) diacrylate based hydrogels to produce human-scale constructs with high-fidelity. Mater Des

  19. 19.

    Huang Y, Zhang XF, Gao G, Yonezawa T, Cui X (2017) 3D bioprinting and the current applications in tissue engineering. Biotechnol J 12:1600734

    Article  Google Scholar 

  20. 20.

    Axpe E, Oyen ML (1976) Applications of alginate-based bioinks in 3D bioprinting. Int J Mol Sci 2016:17

    Google Scholar 

  21. 21.

    Luo Y, Luo G, Gelinsky M, Huang P, Ruan C (2017) 3D bioprinting scaffold using alginate/polyvinyl alcohol bioinks. Mater Lett 189:295–298

    Article  Google Scholar 

  22. 22.

    Daly AC, Critchley SE, Rencsok EM, Kelly DJ (2016) A comparison of different bioinks for 3D bioprinting of fibrocartilage and hyaline cartilage. Biofabrication 8:045002

    Article  Google Scholar 

  23. 23.

    Lee H, Cho D-W (2016) One-step fabrication of an organ-on-a-chip with spatial heterogeneity using a 3D bioprinting technology. Lab Chip 16:2618–2625

    Article  Google Scholar 

  24. 24.

    Jungst T, Smolan W, Schacht K, Scheibel T, Groll J (2015) Strategies and molecular design criteria for 3D printable hydrogels. Chem Rev 116:1496–1539

    Article  Google Scholar 

  25. 25.

    Yue K, Trujillo-de Santiago G, Alvarez MM, Tamayol A, Annabi N, Khademhosseini A (2015) Synthesis, properties, and biomedical applications of gelatin methacryloyl (GelMA) hydrogels. Biomaterials 73:254–271

    Article  Google Scholar 

  26. 26.

    Yin J, Yan M, Wang Y, Fu J, Suo H (2018) 3D bioprinting of low-concentration cell-laden gelatin methacrylate (GelMA) bioinks with a two-step cross-linking strategy. ACS Appl Mater Interfaces 10:6849–6857

    Article  Google Scholar 

  27. 27.

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

    Article  Google Scholar 

  28. 28.

    Bertassoni LE, Cardoso JC, Manoharan V, Cristino AL, Bhise NS, Araujo WA, Zorlutuna P, Vrana NE, Ghaemmaghami AM, Dokmeci MR (2014) Direct-write bioprinting of cell-laden methacrylated gelatin hydrogels. Biofabrication 6:024105

    Article  Google Scholar 

  29. 29.

    Schuurman W, Levett PA, Pot MW, van Weeren PR, Dhert WJA, Hutmacher DW, Melchels FPW, Klein TJ, Malda J (2013) Gelatin-methacrylamide hydrogels as potential biomaterials for fabrication of tissue-engineered cartilage constructs. Macromol Biosci 13:551–561

    Article  Google Scholar 

  30. 30.

    Ouyang L, Highley CB, Sun W, Burdick JA (2017) A generalizable strategy for the 3D bioprinting of hydrogels from nonviscous photo-crosslinkable inks. Adv Mater 29:1604983

    Article  Google Scholar 

  31. 31.

    Ying G-L, Jiang N, Maharjan S, Yin Y-X, Chai R-R, Cao X, Yang J-Z, Miri AK, Hassan S, Zhang YS (2018) Aqueous two-phase emulsion bioink-enabled 3D bioprinting of porous hydrogels. Adv Mater. https://doi.org/10.1002/adma.201805460

    Article  Google Scholar 

  32. 32.

    Colosi C, Shin SR, Manoharan V, Massa S, Constantini M, Barbetta A, Dokmeci MR, Dentini M, Khademhosseini A (2015) Microfluidic bioprinting of heterogeneous 3D tissue constructs using low viscosity bioink. Adv Mater 28:677–684

    Article  Google Scholar 

  33. 33.

    Zhang YS, Arneri A, Bersini S, Shin S-R, Zhu K, Malekabadi ZG, Aleman J, Colosi C, Busignani F, Dell’Erba V, Bishop C, Shupe T, Demarchi D, Moretti M, Rasponi M, Dokmeci MR, Atala A, Khademhosseini A (2016) Bioprinting 3D microfibrous scaffolds for engineering endothelialized myocardium and heart-on-a-chip. Biomaterials 110:45–59

    Article  Google Scholar 

  34. 34.

    Zhang YS, Pi Q, van Genderen AM (2017) Microfluidic bioprinting for engineering vascularized tissues and organoids. J Vis Exp 126:e55957

    Google Scholar 

  35. 35.

    Zhu K, Chen N, Liu X, Mu X, Zhang W, Wang C, Zhang YS (2018) A general strategy for extrusion bioprinting of bio-macromolecular bioinks through alginate-templated dual-stage crosslinking. Macromol Biosci 18:1800127

    Article  Google Scholar 

  36. 36.

    Yetisen AK, Jiang N, Fallahi A, Montelongo Y, Ruiz-Esparza GU, Tamayol A, Zhang YS, Mahmood I, Yang SA, Kim KS (2017) Glucose-sensitive hydrogel optical fibers functionalized with phenylboronic acid. Adv Mater 29:1606380

    Article  Google Scholar 

  37. 37.

    Zhang YS, Davoudi F, Walch P, Manbachi A, Luo X, Dell’Erba V, Miri AK, Albadawi H, Arneri A, Li X, Wang X, Dokmeci MR, Khademhosseini A, Oklu R (2016) Bioprinted thrombosis-on-a-chip. Lab Chip 16:4097–4105

    Article  Google Scholar 

  38. 38.

    Bertassoni LE, Cecconi M, Manoharan V, Nikkhah M, Hjortnaes J, Cristino AL, Barabaschi G, Demarchi D, Dokmeci MR, Yang Y, Khademhosseini A (2014) Hydrogel bioprinted microchannel networks for vascularization of tissue engineering constructs. Lab Chip 14:2202–2211

    Article  Google Scholar 

  39. 39.

    Massa S, Seo J, Arneri A, Bersini S, Cha B-H, Antona S, Enrico A, Gao Y, Hassan S, Cox JPA, Zhang YS, Dokmeci MR, Khademhosseini A, Shin S-R (2017) Bioprinted 3D vascularized tissue model for drug toxicity analysis. Biomicrofluidics 11:044109

    Article  Google Scholar 

  40. 40.

    Zhang YS, Duchamp M, Ellisen LW, Moses MA, Khademhosseini A (2017) Recapitulating mammary ductal carcinoma microenvironment in vitro using sacrificial bioprinting. In: AACR 2017, Washington DC

  41. 41.

    Yu Y, Zhang Y, Martin JA, Ozbolat IT (2013) Evaluation of cell viability and functionality in vessel-like bioprintable cell-laden tubular channels. J Biomech Eng 135:091011–091011

    Article  Google Scholar 

  42. 42.

    Zhang Y, Yu Y, Ozbolat IT (2013) Direct bioprinting of vessel-like tubular microfluidic channels. J Nanotechnol Eng Med 4:020902

    Article  Google Scholar 

  43. 43.

    Zhang Y, Yu Y, Akkouch A, Dababneh A, Dolati F, Ozbolat IT (2015) In vitro study of directly bioprinted perfusable vasculature conduits. Biomater Sci 3:134–143

    Article  Google Scholar 

  44. 44.

    Pi Q, Maharjan S, Yan X, Liu X, Singh B, Van Genderen AM, Robledo-Padilla F, Parra-Saldivar R, Hu N, Jia W, Xu C, Kang J, Hassan S, Cheng H, Hou X, Khademhosseini A, Zhang YS (2018) Digitally tunable microfluidic bioprinting of multilayered cannular tissues. Adv Mater 30:1706913

    Article  Google Scholar 

  45. 45.

    Liu W, Zhong Z, Hu N, Zhou Y, Maggio L, Miri AK, Fragasso A, Jin X, Khademhosseini A, Zhang YS (2018) Coaxial extrusion bioprinting of 3D microfibrous constructs with cell-favorable gelatin methacryloyl microenvironments. Biofabrication 10:024102

    Article  Google Scholar 

  46. 46.

    Ma X, Qu X, Zhu W, Li Y-S, Yuan S, Zhang H, Liu J, Wang P, Lai CSE, Zanella F (2016) Deterministically patterned biomimetic human iPSC-derived hepatic model via rapid 3D bioprinting. Proc Natl Acad Sci 113:2206–2211

    Article  Google Scholar 

  47. 47.

    Han L-H, Mapili G, Chen S, Roy K (2008) Projection microfabrication of three-dimensional scaffolds for tissue engineering. J Manuf Sci Eng 130:021005

    Article  Google Scholar 

  48. 48.

    Miri AK, Nieto D, Iglesias L, Goodarzi Hosseinabadi H, Maharjan S, Ruiz-Esparza GU, Khoshakhlagh P, Manbachi A, Dokmeci MR, Chen S, Shin SR, Zhang YS, Khademhosseini A (2018) Microfluidics-enabled multimaterial maskless stereolithographic bioprinting. Adv Mater 30:1800242

    Article  Google Scholar 

  49. 49.

    Trujillo-de Santiago G, Alvarez MM, Samandari M, Prakash G, Chandrabhatla G, Rellstab-Sánchez PI, Byambaa B, Pour Shahid Saeed Abadi P, Mandla S, Avery RK, Vallejo-Arroyo A, Nasajpour A, Annabi N, Zhang YS, Khademhosseini A (2018) Chaotic printing: using chaos to fabricate densely packed micro- and nanostructures at high resolution and speed. Mater Horizons 5:813–822

    Article  Google Scholar 

Download references

Acknowledgements

The authors gratefully acknowledge funding from the National Institutes of Health (K99CA201603, R21EB025270, R21EB026175) and Doctoral New Investigator Grant from American Chemical Society Petroleum Research Fund (56840-DNI7). G. L. Y. acknowledges Natural and Science Foundation of Hubei Province (2014CFB778).

Author information

Affiliations

Authors

Corresponding authors

Correspondence to Cunjiang Yu or Yu Shrike Zhang.

Ethics declarations

Conflict of interest

The authors declare no conflict of interests.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Ying, G., Jiang, N., Yu, C. et al. Three-dimensional bioprinting of gelatin methacryloyl (GelMA). Bio-des. Manuf. 1, 215–224 (2018). https://doi.org/10.1007/s42242-018-0028-8

Download citation

  • Bioprinting
  • Bioink
  • Gelatin methacryloyl (GelMA)
  • Biofabrication
  • Tissue engineering
  • Tissue model