Skip to main content
Log in

Advanced Bioink Materials for Tissue Engineering Applications

  • Published:
Current Tissue Microenvironment Reports Aims and scope Submit manuscript

Abstract

Purpose of Review

Global demand for organ transplantation or tissue regeneration is constantly increasing. Advances in tissue engineering and regenerative medicine have made it possible to use 3D bioprinting to regenerate such damaged organs and tissues into functional organs and tissues. The main component of 3D bioprinting is bioink, which is essential for the development of functional organs and tissue structures. The purpose of this review is to provide an overview of bioink in context to used materials and methodology to construct bioink and its applications in bioprinting.

Recent Findings

The bioinks used in 3D printing technology have to possess some essential properties like biocompatibility, printability and shape fidelity, which are important and should be considered when choosing an appropriate bioink. A variety of natural, synthetic or combination of these have been used for the production of bioink.

Summary

This review provides an overview of bioinks used in 3D printing in tissue engineering and regenerative medicine applications. Different materials applied successfully for synthesis of bioink are also described in detail. The focus of this review is on the recently reported materials for bioink production and their properties in context to 3D bioprinting.

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.

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References 

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Atala A, Yoo JJ. Essentials of 3D biofabrication and translation. 1st ed. Academic Press; 2015.

  2. Groll J, Burdick JA, Cho DW, Derby B, Gelinsky M, Heilshorn SC, Juengst T, Malda J, Mironov VA, Nakayama K, Ovsianikov A. A definition of bioinks and their distinction from biomaterial inks. Biofabrication. 2018;11(1):013001.

    Article  ADS  CAS  PubMed  Google Scholar 

  3. Li NN, Fane AG, Ho WW, Matsuura T, editors. Tissue Engineering with Membranes. Advanced membrane technology and applications. John Wiley & Sons; 2011. p. 409–427.

  4. Malda J, Visser J, Melchels FP, Jüngst T, Hennink WE, Dhert WJ, Groll J, Hutmacher DW. 25th anniversary article: engineering hydrogels for biofabrication. Adv Mater. 2013;25(36):5011–28.

    Article  CAS  PubMed  Google Scholar 

  5. Melchels FP, Domingos MA, Klein TJ, Malda J, Bartolo PJ, Hutmacher DW. Additive manufacturing of tissues and organs. Prog Polym Sci. 2012;37(8):1079–104.

    Article  CAS  Google Scholar 

  6. Skardal A, Atala A. Biomaterials for integration with 3-D bioprinting. Ann Biomed Eng. 2015;43(3):730–46.

    Article  PubMed  Google Scholar 

  7. Murphy SV, Atala A. 3D bioprinting of tissues and organs. Nat Biotechnol. 2014;32(8):773–85.

    Article  CAS  PubMed  Google Scholar 

  8. Malda J, Groll J. A step towards clinical translation of biofabrication. Trends Biotechnol. 2016;34(5):356–7.

    Article  CAS  PubMed  Google Scholar 

  9. Zhang YS, Xia Y. Multiple facets for extracellular matrix mimicking in regenerative medicine. Nanomedicine. 2015;10(5):689–92.

    Article  CAS  PubMed  Google Scholar 

  10. Leijten J, Rouwkema J, Zhang YS, Nasajpour A, Dokmeci MR, Khademhosseini A. Advancing tissue engineering: a tale of nano, micro and macro scale integration. Small. 2016;10:2130–45.

    Article  Google Scholar 

  11. Tomasina C, Bodet T, Mota C, Moroni L, Camarero-Espinosa S. Bioprinting vasculature: materials, cells and emergent techniques. Materials. 2019;12(17):2701.

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  12. Montero FE, Rezende RA, Da Silva JV, Sabino MA. Development of a smart bioink for bioprinting applications. Front Mech Eng. 2019;5:56.

  13. Bedian L, Villalba-Rodríguez AM, Hernández-Vargas G, Parra-Saldivar R, Iqbal HM. Bio-based materials with novel characteristics for tissue engineering applications–a review. Int J Biol Macromol. 2017;1(98):837–46.

    Article  Google Scholar 

  14. Puluca N, Lee S, Doppler S, Münsterer A, Dreßen M, Krane M, Wu SM. Bioprinting approaches to engineering vascularized 3D cardiac tissues. Curr Cardiol Rep. 2019;21(9):1–1.

    Article  Google Scholar 

  15. Wiles K, Fishman JM, De Coppi P, Birchall MA. The host immune response to tissue-engineered organs: current problems and future directions. Tissue Eng Part B Rev. 2016;22(3):208–19.

    Article  PubMed  Google Scholar 

  16. • Nesic D, Durual S, Marger L, Mekki M, Sailer I, Scherrer SS. Could 3D printing be the future for oral soft tissue regeneration? Bioprinting. 2020;1(20):e00100. Excellent overview on future of 3D bioprinting in therapy.

    Article  Google Scholar 

  17. Cui H, Nowicki M, Fisher JP, Zhang LG. 3D bioprinting for organ regeneration. Adv Healthcare Mater. 2017;6(1):1601118.

    Article  Google Scholar 

  18. Derakhshanfar S, Mbeleck R, Xu K, Zhang X, Zhong W, Xing M. 3D bioprinting for biomedical devices and tissue engineering: a review of recent trends and advances. Bioactive materials. 2018;3(2):144–56.

    Article  PubMed  PubMed Central  Google Scholar 

  19. Matai I, Kaur G, Seyedsalehi A, McClinton A, Laurencin CT. Progress in 3D bioprinting technology for tissue/organ regenerative engineering. Biomaterials. 2020;1(226):119536.

    Article  Google Scholar 

  20. •• Zennifer A, Manivannan S, Sethuraman S, Kumbar SG, Sundaramurthi D. 3D bioprinting and photocrosslinking: emerging strategies & future perspectives. Mater Sci Eng, C. 2021;29:112576. This article describes the use, methodology, and challenges of 3D bioprinting for specific biomedical applications by using bioink and photo-crosslinkers. They also summarize the new directions to create 3D tissue models to study diseases and organ transplantation.

    Google Scholar 

  21. •• Dellaquila A, Le Bao C, Letourneur D, Simon-Yarza T. In vitro strategies to vascularize 3D physiologically relevant models. Advanced Science. 2021;8(19):2100798. Excellent review highlighting the major advancement in prevascularization techniques to build physiological organ-specific 3D models for use in regenerative medicine and drug development in a near future.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Kumari S, Mondal P, Chatterjee K. Digital light processing-based 3D bioprinting of κ-carrageenan hydrogels for engineering cell-loaded tissue scaffolds. Carbohydr Polym. 2022;290:119508.

  23. Shahrubudin N, Lee TC, Ramlan R. An overview on 3D printing technology: technological, materials, and applications. Procedia Manufacturing. 2019;1(35):1286–96.

    Article  Google Scholar 

  24. Attaran M. The rise of 3-D printing: the advantages of additive manufacturing over traditional manufacturing. Bus Horiz. 2017;60(5):677–88.

    Article  Google Scholar 

  25. Zhu Y, Joralmon D, Shan W, Chen Y, Rong J, Zhao H, Xiao S, Li X. 3D printing biomimetic materials and structures for biomedical applications. Bio-Design and Manufacturing. 2021;4(2):405–28.

    Article  Google Scholar 

  26. Hospodiuk M, Dey M, Sosnoski D, Ozbolat IT. The bioink: a comprehensive review on bioprintable materials. Biotechnol Adv. 2017;35(2):217–39.

    Article  CAS  PubMed  Google Scholar 

  27. •• Chimene D, Kaunas R, Gaharwar AK. Hydrogel bioink reinforcement for additive manufacturing: a focused review of emerging strategies. Adv Mater. 2020;32(1):1902026. Excelllent review showing the current state of the art on hydrogel based bioink.

    Article  CAS  Google Scholar 

  28. Das S, Basu B. An overview of hydrogel-based bioinks for 3D bioprinting of soft tissues. J Indian Inst Sci. 2019;99(3):405–28.

    Article  Google Scholar 

  29. Rastogi P, Kandasubramanian B. Breakthrough in the printing tactics for stimuli-responsive materials: 4D printing. Chem Eng J. 2019;15(366):264–304.

    Article  Google Scholar 

  30. • Brunel LG, Hull SM, Heilshorn S. Engineered assistive materials for 3D bioprinting:support baths and sacrificial inks. Biofabrication. 2022;14(3):032001. Excellent overview of assistive materials that provide physical confinement during the printing process to improve resolution and shape fidelity.

  31. Mota C, Camarero-Espinosa S, Baker MB, Wieringa P, Moroni L. Bioprinting: from tissue and organ development to in vitro models. Chem Rev. 2020;120(19):10547–607.

    Article  CAS  PubMed  Google Scholar 

  32. Rutz AL, Gargus ES, Hyland KE, Lewis PL, Setty A, Burghardt WR, Shah RN. Employing PEG crosslinkers to optimize cell viability in gel phase bioinks and tailor post printing mechanical properties. Acta Biomater. 2019;1(99):121–32.

    Article  Google Scholar 

  33. •• Piras CC, Smith DK. Multicomponent polysaccharide alginate-based bioinks. J Mater Chem B. 2020;8(36):8171–88. A focused review that provide the idea on how to identify different alginate-polysaccharide bioink formulations for distinct applications.

    Article  CAS  PubMed  Google Scholar 

  34. Camacho P, Busari H, Seims KB, Tolbert JW, Chow LW. Materials as bioinks and bioink design. In: 3D bioprinting in medicine. Cham: Springer; 2019. p. 67–100.

  35. Cofiño C, Perez-Amodio S, Semino CE, Engel E, Mateos-Timoneda MA. Development of a self-assembled peptide/methylcellulose-based bioink for 3D bioprinting. Macromol Mater Eng. 2019;304(11):1900353.

    Article  Google Scholar 

  36. Ying GL, Jiang N, Maharjan S, Yin YX, Chai RR, Cao X, Yang JZ, Miri AK, Hassan S, Zhang YS. Aqueous two-phase emulsion bioink-enabled 3D bioprinting of porous hydrogels. Adv Mater. 2018;30(50):1805460.

    Article  Google Scholar 

  37. Mobaraki M, Ghaffari M, Yazdanpanah A, Luo Y, Mills DK. Bioinks and bioprinting: a focused review. Bioprinting. 2020;1(18):e00080.

    Article  Google Scholar 

  38. Trampe E, Koren K, Akkineni AR, Senwitz C, Krujatz F, Lode A, Gelinsky M, Kühl M. Functionalized bioink with optical sensor nanoparticles for O2 imaging in 3D-bioprinted constructs. Adv Func Mater. 2018;28(45):1804411.

    Article  Google Scholar 

  39. Shin S, Kwak H, Hyun J. Melanin nanoparticle-incorporated silk fibroin hydrogels for the enhancement of printing resolution in 3D-projection stereolithography of poly (ethylene glycol)-tetraacrylate bio-ink. ACS Appl Mater Interfaces. 2018;10(28):23573–82.

    Article  CAS  PubMed  Google Scholar 

  40. • Diaz-Gomez L, Elizondo ME, Koons GL, Diba M, Chim LK, Cosgriff-Hernandez E, Melchiorri AJ, Mikos AG. Fiber engraving for bioink bioprinting within 3D printed tissue engineering scaffolds. Bioprinting. 2020;1(18):e00076. This work emphasizes the novel 3D printing method to fabricate the multimaterial scaffolds by the combination of thermoplastic extrusion and low temperature extrusion of bioinks.

    Article  Google Scholar 

  41. Neto MD, Oliveira MB, Mano JF. Microparticles in contact with cells: from carriers to multifunctional tissue modulators. Trends Biotechnol. 2019;37(9):1011–28.

    Article  CAS  PubMed  Google Scholar 

  42. Chen J, Huang D, Wang L, Hou J, Zhang H, Li Y, Zhong S, Wang Y, Wu Y, Huang W. 3D bioprinted multiscale composite scaffolds based on gelatin methacryloyl (GelMA)/chitosan microspheres as a modular bioink for enhancing 3D neurite outgrowth and elongation. J Colloid Interface Sci. 2020;15(574):162–73.

    Article  ADS  Google Scholar 

  43. Jain K, Shukla R, Yadav A, Ujjwal RR, Flora SJ. 3D printing in development of nanomedicines. Nanomaterials. 2021;11(2):420.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Khoeini R, Nosrati H, Akbarzadeh A, Eftekhari A, Kavetskyy T, Khalilov R, Ahmadian E, Nasibova A, Datta P, Roshangar L, Deluca DC. Natural and synthetic bioinks for 3D bioprinting. Advanced NanoBiomed Research. 2021;1(8):2000097.

    Article  CAS  Google Scholar 

  45. Bertlein S, Brown G, Lim KS, Jungst T, Boeck T, Blunk T, Tessmar J, Hooper GJ, Woodfield TB, Groll J. Thiol–ene clickable gelatin: a platform bioink for multiple 3D biofabrication technologies. Adv Mater. 2017;29(44):1703404.

    Article  Google Scholar 

  46. Lee SJ, Lee JH, Park J, Kim WD, Park SA. Fabrication of 3D printing scaffold with porcine skin decellularized bio-ink for soft tissue engineering. Materials. 2020;13(16):3522.

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  47. Kim SH, Yeon YK, Lee JM, Chao JR, Lee YJ, Seo YB, Sultan M, Lee OJ, Lee JS, Yoon SI, Hong IS. Precisely printable and biocompatible silk fibroin bioink for digital light processing 3D printing. Nat Commun. 2018;9(1):1–4.

    ADS  Google Scholar 

  48. Indurkar A, Bangde P, Gore M, Reddy P, Jain R, Dandekar P. Optimization of guar gum-gelatin bioink for 3D printing of mammalian cells. Bioprinting. 2020;1(20):e00101.

    Article  Google Scholar 

  49. Habib A, Khoda B. Development of clay based novel hybrid bio-ink for 3D bio-printing process. J Manuf Process. 2019;1(38):76–87.

    Article  Google Scholar 

  50. Jeon O, Lee YB, Jeong H, Lee SJ, Wells D, Alsberg E. Individual cell-only bioink and photocurable supporting medium for 3D printing and generation of engineered tissues with complex geometries. Mater Horiz. 2019;6(8):1625–31.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Gao G, Lee JH, Jang J, Lee DH, Kong JS, Kim BS, Choi YJ, Jang WB, Hong YJ, Kwon SM, Cho DW. Tissue engineered bio-blood-vessels constructed using a tissue-specific bioink and 3D coaxial cell printing technique: a novel therapy for ischemic disease. Adv Func Mater. 2017;27(33):1700798.

    Article  Google Scholar 

  52. Petta D, D’amora U, Ambrosio L, Grijpma DW, Eglin D, D’este M. Hyaluronic acid as a bioink for extrusion-based 3D printing. Biofabrication. 2020;12(3):032001.

    Article  ADS  CAS  PubMed  Google Scholar 

  53. Antich C, de Vicente J, Jiménez G, Chocarro C, Carrillo E, Montañez E, Gálvez-Martín P, Marchal JA. Bio-inspired hydrogel composed of hyaluronic acid and alginate as a potential bioink for 3D bioprinting of articular cartilage engineering constructs. Acta Biomater. 2020;1(106):114–23.

    Article  Google Scholar 

  54. Jung CS, Kim BK, Lee J, Min BH, Park SH. Development of printable natural cartilage matrix bioink for 3D printing of irregular tissue shape. Tissue Eng Regen Med. 2018;15(2):155–62.

    Article  CAS  PubMed  Google Scholar 

  55. Jiang Y, Zhou J, Yang Z, Liu D, Xv X, Zhao G, Shi H, Zhang Q. Dialdehyde cellulose nanocrystal/gelatin hydrogel optimized for 3D printing applications. J Mater Sci. 2018;53(16):11883–900.

    Article  ADS  CAS  Google Scholar 

  56. Kim J, Kong JS, Kim H, Han W, Won JY, Cho DW. Maturation and protection effect of retinal tissue-derived bioink for 3D cell printing technology. Pharmaceutics. 2021;13(7):934.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Suo H, Zhang J, Xu M, Wang L. Low-temperature 3D printing of collagen and chitosan composite for tissue engineering. Mater Sci Eng, C. 2021;1(123):111963.

    Article  Google Scholar 

  58. Chen P, Zheng L, Wang Y, Tao M, Xie Z, Xia C, Gu C, Chen J, Qiu P, Mei S, Ning L. Desktop-stereolithography 3D printing of a radially oriented extracellular matrix/mesenchymal stem cell exosome bioink for osteochondral defect regeneration. Theranostics. 2019;9(9):2439.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Mazzocchi A, Devarasetty M, Huntwork R, Soker S, Skardal A. Optimization of collagen type I-hyaluronan hybrid bioink for 3D bioprinted liver microenvironments. Biofabrication. 2018;11(1):015003.

    Article  ADS  PubMed  PubMed Central  Google Scholar 

  60. Abelseth E, Abelseth L, De la Vega L, Beyer ST, Wadsworth SJ, Willerth SM. 3D printing of neural tissues derived from human induced pluripotent stem cells using a fibrin-based bioink. ACS Biomater Sci Eng. 2018;5(1):234–43.

    Article  PubMed  Google Scholar 

  61. Yang X, Lu Z, Wu H, Li W, Zheng L, Zhao J. Collagen-alginate as bioink for three-dimensional (3D) cell printing based cartilage tissue engineering. Mater Sci Eng, C. 2018;1(83):195–201.

    Article  Google Scholar 

  62. Li L, Qin S, Peng J, Chen A, Nie Y, Liu T, Song K. Engineering gelatin-based alginate/carbon nanotubes blend bioink for direct 3D printing of vessel constructs. Int J Biol Macromol. 2020;15(145):262–71.

    Article  Google Scholar 

  63. Celikkin N, Simó Padial J, Costantini M, Hendrikse H, Cohn R, Wilson CJ, Rowan AE, Święszkowski W. 3D printing of thermoresponsive polyisocyanide (PIC) hydrogels as bioink and fugitive material for tissue engineering. Polymers. 2018;10(5):555.

    Article  PubMed  PubMed Central  Google Scholar 

  64. Echalier C, Levato R, Mateos-Timoneda MA, Castaño O, Déjean S, Garric X, Pinese C, Noel D, Engel E, Martinez J, Mehdi A. Modular bioink for 3D printing of biocompatible hydrogels: sol–gel polymerization of hybrid peptides and polymers. RSC Adv. 2017;7(20):12231–5.

    Article  ADS  CAS  Google Scholar 

  65. Ahlfeld T, Cidonio G, Kilian D, Duin S, Akkineni AR, Dawson JI, Yang S, Lode A, Oreffo RO, Gelinsky M. Development of a clay based bioink for 3D cell printing for skeletal application. Biofabrication. 2017;9(3):034103.

    Article  ADS  CAS  PubMed  Google Scholar 

  66. Habib MA, Khoda B. Development of clay based novel bio-ink for 3D bio-printing process. Procedia Manufacturing. 2018;1(26):846–56.

    Article  Google Scholar 

  67. Rastin H, Zhang B, Bi J, Hassan K, Tung TT, Losic D. 3D printing of cell-laden electroconductive bioinks for tissue engineering applications. Journal of Materials Chemistry B. 2020;8(27):5862–76.

    Article  CAS  PubMed  Google Scholar 

  68. •• Van Belleghem S, Mahadik B, Snodderly K, Mote Z, Jiang B, Yu JR, McLoughlin S, He X, Nam AJ, Fisher JP. Dual extrusion patterning drives tissue development aesthetics and shape retention in 3D printed nipple-areola constructs. Adv Healthcare Mater. 2021;10(23):2101249. Construction of 3D printed hybrid scaffolds composed of complementary biodegradable gelatin methacrylate and synthetic non-degradable poly(ethylene) glycol hydrogels to foster the regeneration of a viable nipple-areola complex

    Article  Google Scholar 

  69. Chimene D, Miller L, Cross LM, Jaiswal MK, Singh I, Gaharwar AK. Nanoengineered osteoinductive bioink for 3D bioprinting bone tissue. ACS Appl Mater Interfaces. 2020;12(14):15976–88.

    Article  CAS  PubMed  Google Scholar 

  70. Chen Y, Wang Y, Yang Q, Liao Y, Zhu B, Zhao G, Shen R, Lu X, Qu S. A novel thixotropic magnesium phosphate-based bioink with excellent printability for application in 3D printing. J Mater Chem B. 2018;6(27):4502–13.

    Article  CAS  PubMed  Google Scholar 

  71. Vancauwenberghe V, Mbong VB, Vanstreels E, Verboven P, Lammertyn J, Nicolai B. 3D printing of plant tissue for innovative food manufacturing: encapsulation of alive plant cells into pectin based bio-ink. J Food Eng. 2019;1(263):454–64.

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Utkarsh Jain.

Ethics declarations

Conflict of Interest

The authors declare no competing interests.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Chauhan, N., Saxena, K., Rawal, R. et al. Advanced Bioink Materials for Tissue Engineering Applications. Curr. Tissue Microenviron. Rep. 5, 13–23 (2024). https://doi.org/10.1007/s43152-023-00050-1

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s43152-023-00050-1

Keywords

Navigation