Skip to main content
SpringerLink
Log in

Advanced Bioinks for 3D Printing: A Materials Science Perspective

  • Emerging Trends in Biomaterials Research
  • Published:
Annals of Biomedical Engineering Aims and scope Submit manuscript

Abstract

Advanced bioinks for 3D printing are rationally designed materials intended to improve the functionality of printed scaffolds outside the traditional paradigm of the “biofabrication window”. While the biofabrication window paradigm necessitates compromise between suitability for fabrication and ability to accommodate encapsulated cells, recent developments in advanced bioinks have resulted in improved designs for a range of biofabrication platforms without this tradeoff. This has resulted in a new generation of bioinks with high print fidelity, shear-thinning characteristics, and crosslinked scaffolds with high mechanical strength, high cytocompatibility, and the ability to modulate cellular functions. In this review, we describe some of the promising strategies being pursued to achieve these goals, including multimaterial, interpenetrating network, nanocomposite, and supramolecular bioinks. We also provide an overview of current and emerging trends in advanced bioink synthesis and biofabrication, and evaluate the potential applications of these novel biomaterials to clinical use.

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

Figure 1
Figure 2

Adapted and reproduced by permission from Wiley58© 2015 and Nature American Inc.35© 2016.

Figure 3

Adapted and reproduced by permission from American Association for the Advancement of Science29© 2015.

Figure 4

Adapted and reproduced by permission from Wiley31© 2015.

Figure 5

Adapted and reproduced by permission from American Chemical Society66© 2015.

Figure 6

Adapted and reproduced by permission from Wiley28© 2015.

Figure 7

Adapted and reproduced by permission from Wiley37© 2015.

Similar content being viewed by others

References

  1. Augst, A. D., H. J. Kong, and D. J. Mooney. Alginate hydrogels as biomaterials. Macromol. Biosci. 6:623–633, 2006.

    Article  CAS  PubMed  Google Scholar 

  2. Azagarsamy, M. A., and K. S. Anseth. Bioorthogonal click chemistry: an indispensable tool to create multifaceted cell culture scaffolds. ACS Macro Lett. 2:5–9, 2012.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Bakarich, S. E., R. Gorkin, M. I. H. Panhuis, and G. M. Spinks. 4D printing with mechanically robust, thermally actuating hydrogels. Macromol. Rapid Commun. 36:1211–1217, 2015.

    Article  CAS  PubMed  Google Scholar 

  4. Bertassoni, L. E., J. C. Cardoso, V. Manoharan, A. L. Cristino, N. S. Bhise, W. A. Araujo, P. Zorlutuna, N. E. Vrana, A. M. Ghaemmaghami, and M. R. Dokmeci. Direct-write bioprinting of cell-laden methacrylated gelatin hydrogels. Biofabrication 6:024105, 2014.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Bertassoni, L. E., M. Cecconi, V. Manoharan, M. Nikkhah, J. Hjortnaes, A. L. Cristino, G. Barabaschi, D. Demarchi, M. R. Dokmeci, and Y. Yang. Hydrogel bioprinted microchannel networks for vascularization of tissue engineering constructs. Lab Chip 14:2202–2211, 2014.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Bhattacharjee, T., S. M. Zehnder, K. G. Rowe, S. Jain, R. M. Nixon, W. G. Sawyer, and T. E. Angelini. Writing in the granular gel medium. Sci. Adv. 1:e1500655, 2015.

    Article  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  8. Carrow, J. K., and A. K. Gaharwar. Bioinspired polymeric nanocomposites for regenerative medicine. Macromol. Chem. Phys. 216:248–264, 2015.

    Article  CAS  Google Scholar 

  9. Chen, Q., H. Chen, L. Zhu, and J. Zheng. Fundamentals of double network hydrogels. J Mater Chem B 3:3654–3676, 2015.

    Article  CAS  Google Scholar 

  10. Chen, Q., L. Zhu, L. Huang, H. Chen, K. Xu, Y. Tan, P. Wang, and J. Zheng. Fracture of the physically cross-linked first network in hybrid double network hydrogels. Macromolecules 47:2140–2148, 2014.

    Article  CAS  Google Scholar 

  11. Chimene, D., D. L. Alge, and A. K. Gaharwar. Two-dimensional nanomaterials for biomedical applications: emerging trends and future prospects. Adv. Mater. 27:7261–7284, 2015.

    Article  CAS  PubMed  Google Scholar 

  12. Chung, J. H., S. Naficy, Z. Yue, R. Kapsa, A. Quigley, S. E. Moulton, and G. G. Wallace. Bio-ink properties and printability for extrusion printing living cells. Biomater. Sci. 1:763–773, 2013.

    Article  CAS  Google Scholar 

  13. Discher, D. E., D. J. Mooney, and P. W. Zandstra. Growth factors, matrices, and forces combine and control stem cells. Science 324:1673–1677, 2009.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Duan, B., E. Kapetanovic, L. A. Hockaday, and J. T. Butcher. Three-dimensional printed trileaflet valve conduits using biological hydrogels and human valve interstitial cells. Acta Biomater. 10:1836–1846, 2014.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Durmus, N. G., S. Tasoglu, and U. Demirci. Bioprinting: functional droplet networks. Nat. Mater. 12:478–479, 2013.

    Article  CAS  PubMed  Google Scholar 

  16. Engler, A. J., S. Sen, H. L. Sweeney, and D. E. Discher. Matrix elasticity directs stem cell lineage specification. Cell 126:677–689, 2006.

    Article  CAS  PubMed  Google Scholar 

  17. Fisher, O. Z., A. Khademhosseini, R. Langer, and N. A. Peppas. Bioinspired materials for controlling stem cell fate. Acc. Chem. Res. 43:419–428, 2010.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Gaharwar, A. K., A. Arpanaei, T. L. Andresen, and A. Dolatshahi-Pirouz. 3D biomaterial microarrays for regenerative medicine: current state-of-the-art, emerging directions and future trends. Adv. Mater. 28:771–781, 2016.

    Article  CAS  PubMed  Google Scholar 

  19. Gaharwar, A. K., R. K. Avery, A. Assmann, A. Paul, G. H. McKinley, A. Khademhosseini, and B. D. Olsen. Shear-thinning nanocomposite hydrogels for the treatment of hemorrhage. ACS Nano 8:9833–9842, 2014.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Gaharwar, A. K., N. A. Peppas, and A. Khademhosseini. Nanocomposite hydrogels for biomedical applications. Biotechnol. Bioeng. 111:441–453, 2014.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Gaharwar, A. K., C. P. Rivera, C.-J. Wu, and G. Schmidt. Transparent, elastomeric and tough hydrogels from poly (ethylene glycol) and silicate nanoparticles. Acta Biomater. 7:4139–4148, 2011.

    Article  CAS  PubMed  Google Scholar 

  22. Gao, G., A. F. Schilling, T. Yonezawa, J. Wang, G. Dai, and X. Cui. Bioactive nanoparticles stimulate bone tissue formation in bioprinted three-dimensional scaffold and human mesenchymal stem cells. Biotechnol. J. 9:1304–1311, 2014.

    Article  CAS  PubMed  Google Scholar 

  23. Gasperini, L., J. F. Mano, and R. L. Reis. Natural polymers for the microencapsulation of cells. J. R. Soc. Interface 11:20140817, 2014.

    Article  PubMed  PubMed Central  Google Scholar 

  24. Goenka, S., V. Sant, and S. Sant. Graphene-based nanomaterials for drug delivery and tissue engineering. J. Control. Release 173:75–88, 2014.

    Article  CAS  PubMed  Google Scholar 

  25. Guilak, F., D. M. Cohen, B. T. Estes, J. M. Gimble, W. Liedtke, and C. S. Chen. Control of stem cell fate by physical interactions with the extracellular matrix. Cell Stem Cell 5:17–26, 2009.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Haque, M. A., T. Kurokawa, and J. P. Gong. Super tough double network hydrogels and their application as biomaterials. Polymer 53:1805–1822, 2012.

    Article  CAS  Google Scholar 

  27. Hart, L. R., J. L. Harries, B. W. Greenland, H. M. Colquhoun, and W. Hayes. Healable supramolecular polymers. Polymer Chemistry 4:4860–4870, 2013.

    Article  CAS  Google Scholar 

  28. Highley, C. B., C. B. Rodell, and J. A. Burdick. Direct 3D printing of shear-thinning hydrogels into self-healing hydrogels. Adv. Mater. 27:5075–5079, 2015.

    Article  CAS  PubMed  Google Scholar 

  29. Hinton, T. J., Q. Jallerat, R. N. Palchesko, J. H. Park, M. S. Grodzicki, H.-J. Shue, M. H. Ramadan, A. R. Hudson, and A. W. Feinberg. Three-dimensional printing of complex biological structures by freeform reversible embedding of suspended hydrogels. Sci. Adv. 1:e1500758, 2015.

    Article  PubMed  PubMed Central  Google Scholar 

  30. Hoffman, A. S. Hydrogels for biomedical applications. Adv. Drug Deliv. Rev. 64:18–23, 2012.

    Article  Google Scholar 

  31. Hong, S., D. Sycks, H. F. Chan, S. Lin, G. P. Lopez, F. Guilak, K. W. Leong, and X. Zhao. 3D printing of highly stretchable and tough hydrogels into complex, cellularized structures. Adv. Mater. 27:4035–4040, 2015.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Huang, T., H. G. Xu, K. X. Jiao, L. P. Zhu, H. R. Brown, and H. L. Wang. A novel hydrogel with high mechanical strength: a macromolecular microsphere composite hydrogel. Adv. Mater. 19:1622–1626, 2007.

    Article  CAS  Google Scholar 

  33. Jaiswal, M. K., J. R. Xavier, J. K. Carrow, P. Desai, D. Alge, and A. K. Gaharwar. Mechanically stiff nanocomposite hydrogels at ultralow nanoparticle content. ACS Nano 10:246–256, 2016.

    Article  CAS  PubMed  Google Scholar 

  34. Jakab, K., C. Norotte, F. Marga, K. Murphy, G. Vunjak-Novakovic, and G. Forgacs. Tissue engineering by self-assembly and bio-printing of living cells. Biofabrication 2:022001, 2010.

    Article  PubMed  PubMed Central  Google Scholar 

  35. Kang, H.-W., S. J. Lee, I. K. Ko, C. Kengla, J. J. Yoo, and A. Atala. A 3D bioprinting system to produce human-scale tissue constructs with structural integrity. Nat. Biotechnol. 34:312–319, 2016.

    Article  CAS  PubMed  Google Scholar 

  36. Kerativitayanan, P., J. K. Carrow, and A. K. Gaharwar. Nanomaterials for engineering stem cell responses. Adv. Healthc Mater. 4:1600–1627, 2015.

    Article  CAS  PubMed  Google Scholar 

  37. Kesti, M., M. Müller, J. Becher, M. Schnabelrauch, M. D’Este, D. Eglin, and M. Zenobi-Wong. A versatile bioink for three-dimensional printing of cellular scaffolds based on thermally and photo-triggered tandem gelation. Acta Biomater. 11:162–172, 2015.

    Article  CAS  PubMed  Google Scholar 

  38. Kirchmajer, D. M., R. Gorkin, III, and M. I. H. Panhuis. An overview of the suitability of hydrogel-forming polymers for extrusion-based 3D-printing. J. Mater. Chem. B 3:4105–4117, 2015.

    Article  CAS  Google Scholar 

  39. Kirchmajer, D. M., and M. I. H. Panhuis. Robust biopolymer based ionic-covalent entanglement hydrogels with reversible mechanical behaviour. J. Mater. Chem. B 2:4694–4702, 2014.

    Article  CAS  Google Scholar 

  40. Kloxin, A. M., C. J. Kloxin, C. N. Bowman, and K. S. Anseth. Mechanical properties of cellularly responsive hydrogels and their experimental determination. Adv. Mater. 22:3484–3494, 2010.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Lee, V. K., D. Y. Kim, H. Ngo, Y. Lee, L. Seo, S.-S. Yoo, P. A. Vincent, and G. Dai. Creating perfused functional vascular channels using 3D bio-printing technology. Biomaterials 35:8092–8102, 2014.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Lee, V., G. Singh, J. P. Trasatti, C. Bjornsson, X. Xu, T. N. Tran, S.-S. Yoo, G. Dai, and P. Karande. Design and fabrication of human skin by three-dimensional bioprinting. Tissue Eng. Part C Methods 20:473–484, 2013.

    Article  PubMed  PubMed Central  Google Scholar 

  43. Malda, J., and J. Groll. A step towards clinical translation of biofabrication. Trends Biotechnol. 34:356, 2016.

    Article  CAS  PubMed  Google Scholar 

  44. Malda, J., J. Visser, F. P. Melchels, T. Jüngst, W. E. Hennink, W. J. Dhert, J. Groll, and D. W. Hutmacher. 25th anniversary article: engineering hydrogels for biofabrication. Adv. Mater. 25:5011–5028, 2013.

    Article  CAS  PubMed  Google Scholar 

  45. Markstedt, K., A. Mantas, I. Tournier, H. C. Martínez Ávila, D. Hägg, and P. Gatenholm. 3D Bioprinting human chondrocytes with nanocellulose-alginate bioink for cartilage tissue engineering applications. Biomacromolecules 16:1489–1496, 2015.

    Article  CAS  PubMed  Google Scholar 

  46. Melchels, F. P., M. A. Domingos, T. J. Klein, J. Malda, P. J. Bartolo, and D. W. Hutmacher. Additive manufacturing of tissues and organs. Prog. Polym. Sci. 37:1079–1104, 2012.

    Article  CAS  Google Scholar 

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

    Article  PubMed  Google Scholar 

  48. Mironov, V., R. P. Visconti, V. Kasyanov, G. Forgacs, C. J. Drake, and R. R. Markwald. Organ printing: tissue spheroids as building blocks. Biomaterials 30:2164–2174, 2009.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Murphy, S. V., and A. Atala. 3D bioprinting of tissues and organs. Nat. Biotechnol. 32:773–785, 2014.

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  Google Scholar 

  51. Parani, M., G. Lokhande, A. Singh, and A. K. Gaharwar. Engineered nanomaterials for infection control and healing acute and chronic wounds. ACS Appl. Mater. Interfaces 8:10049–10069, 2016.

    Article  CAS  PubMed  Google Scholar 

  52. Pati, F., J. Gantelius, and H. A. Svahn. 3D bioprinting of tissue/organ models. Angew. Chem. Int. Ed. 55:4650–4665, 2016.

    Article  CAS  Google Scholar 

  53. Pati, F., J. Jang, D.-H. Ha, S. Won Kim, J.-W. Rhie, J.-H. Shim, D.-H. Kim, and D.-W. Cho. Printing three-dimensional tissue analogues with decellularized extracellular matrix bioink. Nat. Commun. 5:3935, 2014.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Paul, A. Nanocomposite hydrogels: an emerging biomimetic platform for myocardial therapy and tissue engineering. Nanomedicine 10:1371–1374, 2015.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Peak, C. W., J. K. Carrow, A. Thakur, A. Singh, and A. K. Gaharwar. Elastomeric cell-laden nanocomposite microfibers for engineering complex tissues. Cell. Mol. Bioeng. 8:404–415, 2015.

    Article  CAS  Google Scholar 

  56. Pereira, R. F., H. A. Almeida, and P. J. Bártolo. Drug delivery systems: advanced technologies potentially applicable in personalised treatmentBiofabrication Hydrogel Constr., Dordrecht: Springer, pp. 225–254, 2013.

    Book  Google Scholar 

  57. Rowley, J. A., G. Madlambayan, and D. J. Mooney. Alginate hydrogels as synthetic extracellular matrix materials. Biomaterials 20:45–53, 1999.

    Article  CAS  PubMed  Google Scholar 

  58. Rutz, A. L., K. E. Hyland, A. E. Jakus, W. R. Burghardt, and R. N. Shah. A multimaterial bioink method for 3D printing tunable, Cell-compatible hydrogels. Adv. Mater. 27:1607–1614, 2015.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Skardal, A., and A. Atala. Biomaterials for Integration with 3-D Bioprinting. Ann. Biomed. Eng. 43:730–746, 2015.

    Article  PubMed  Google Scholar 

  60. Slaughter, B. V., S. S. Khurshid, O. Z. Fisher, A. Khademhosseini, and N. A. Peppas. Hydrogels in regenerative medicine. Adv. Mater. 21:3307–3329, 2009.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Stanton, M., J. Samitier, and S. Sánchez. Bioprinting of 3D hydrogels. Lab Chip 15:3111–3115, 2015.

    Article  CAS  PubMed  Google Scholar 

  62. Suekama, T. C., J. Hu, T. Kurokawa, J. P. Gong, and S. H. Gehrke. Double-network strategy improves fracture properties of chondroitin sulfate networks. ACS Macro Lett. 2:137–140, 2013.

    Article  CAS  Google Scholar 

  63. Thakur, T., J. R. Xavier, L. Cross, M. K. Jaiswal, E. Mondragon, R. Kaunas, and A. K. Gaharwar. Photocrosslinkable and elastomeric hydrogels for bone regeneration. J Biomed Mater Res A 104:879–888, 2016.

    Article  CAS  PubMed  Google Scholar 

  64. Thiele, J., Y. Ma, S. Bruekers, S. Ma, and W. T. Huck. 25th Anniversary article: designer hydrogels for cell cultures: a materials selection guide. Adv. Mater. 26:125–148, 2014.

    Article  CAS  PubMed  Google Scholar 

  65. Tibbitt, M. W., and K. S. Anseth. Hydrogels as extracellular matrix mimics for 3D cell culture. Biotechnol. Bioeng. 103:655–663, 2009.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Xavier, J. R., T. Thakur, P. Desai, M. K. Jaiswal, N. Sears, E. Cosgriff-Hernandez, R. Kaunas, and A. K. Gaharwar. Bioactive nanoengineered hydrogels for bone tissue engineering: a growth-factor-free approach. ACS Nano 9:3109–3118, 2015.

    Article  CAS  PubMed  Google Scholar 

  67. Xu, Y., and X. Wang. Application of 3D biomimetic models in drug delivery and regenerative medicine. Curr. Pharm. Des. 21:1618–1626, 2015.

    Article  CAS  PubMed  Google Scholar 

  68. Yang, L., X. Tan, Z. Wang, and X. Zhang. Supramolecular polymers: historical development, preparation, characterization, and functions. Chem. Rev. 115:7196–7239, 2015.

    Article  CAS  PubMed  Google Scholar 

  69. Zhu, W., X. Ma, M. Gou, D. Mei, K. Zhang, and S. Chen. 3D printing of functional biomaterials for tissue engineering. Curr. Opin. Biotechnol. 40:103–112, 2016.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This research was supported by the National Science Foundation Award No. HRD-1406755 and CBET-1264848 and NIH R01 AR066033-01.

Author information

Authors and Affiliations

  1. Department of Biomedical Engineering, Texas A&M University, College Station, TX, 77843, USA

    David Chimene, Kimberly K. Lennox, Roland R. Kaunas & Akhilesh K. Gaharwar

  2. Department of Materials Science and Engineering, Texas A&M University, College Station, TX, 77843, USA

    Akhilesh K. Gaharwar

  3. Center for Remote Health Technologies and Systems, Texas A&M University, College Station, TX, 77843, USA

    Akhilesh K. Gaharwar

Authors
  1. David Chimene
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Kimberly K. Lennox
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Roland R. Kaunas
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Akhilesh K. Gaharwar
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Akhilesh K. Gaharwar.

Additional information

Associate Editor Michael S. Detamore oversaw the review of this article.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Chimene, D., Lennox, K.K., Kaunas, R.R. et al. Advanced Bioinks for 3D Printing: A Materials Science Perspective. Ann Biomed Eng 44, 2090–2102 (2016). https://doi.org/10.1007/s10439-016-1638-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10439-016-1638-y

Keywords

Search

Navigation