Skip to main content
Log in

Synthesis of easily-processable collagen bio-inks using ionic liquid for 3D bioprinted liver tissue models with branched vascular networks

  • Articles
  • Published:
Science China Chemistry Aims and scope Submit manuscript

Abstract

Bioprinting has been a flouring way to fabricate complex tissue and organ mimics via precisely depositing printable cell-laden biomaterials. However, there is a limited number of biomaterials that fulfill the mechanical property of printing while meeting the responsive environment desired for the cells. Despite excellent cell compatibility and bioactivity, collagen suffers from difficulties in processing and printability which inhibited its utilization in three-dimensional (3D) bioprinting. Herein, we address this limitation by using ionic liquid as the solvent in the modification process, enabling collagens modified with quantified norbornene for chemical crosslink and extrusion-based 3D printing. With improved solubility and rheological properties, norbornene-functionalized collagen (Col-Nor) exhibited better shape fidelity in extrusion-based 3D printing compared with the one before modification. Photo-crosslinked Col-Nor hydrogel provided structural support and promoted the adhesion, proliferation, and differentiation of various types of cells, which afforded a centimeter-scale liver tissue model. This highly generalizable methodology expands printable, versatile, and tunable hydrogels developed from the natural extracellular matrix, allowing the biofabrication of 3D liver tissue model with branched vascular networks.

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. Hofer M, Lutolf MP. Nat Rev Mater, 2021, 6: 402–420

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Takebe T, Wells JM. Science, 2019, 364: 956–959

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Dekkers JF, van Vliet EJ, Sachs N, Rosenbluth JM, Kopper O, Rebel HG, Wehrens EJ, Piani C, Visvader JE, Verissimo CS, Boj SF, Brugge JS, Clevers H, Rios AC. Nat Protoc, 2021, 16: 1936–1965

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Broutier L, Mastrogiovanni G, Verstegen MM, Francies HE, Gavarró LM, Bradshaw CR, Allen GE, Arnes-Benito R, Sidorova O, Gaspersz MP, Georgakopoulos N, Koo BK, Dietmann S, Davies SE, Praseedom RK, Lieshout R, IJzermans JNM, Wigmore SJ, Saeb-Parsy K, Garnett MJ, van der Laan LJ, Huch M. Nat Med, 2017, 23: 1424–1435

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Mukhopadhyay M. Nat Methods, 2021, 18: 596

    Article  CAS  PubMed  Google Scholar 

  6. Fyfe I. Nat Rev Neurol, 2021, 17: 1

    Article  PubMed  Google Scholar 

  7. Li X, Liu B, Pei B, Chen J, Zhou D, Peng J, Zhang X, Jia W, Xu T. Chem Rev, 2020, 120: 10793–10833

    Article  CAS  PubMed  Google Scholar 

  8. Ng WL, Lee JM, Zhou M, Chen YW, Lee KXA, Yeong WY, Shen YF. Biofabrication, 2020, 12: 022001

    Article  CAS  PubMed  Google Scholar 

  9. Jiang T, Munguia-Lopez JG, Flores-Torres S, Kort-Mascort J, Kinsella JM. Appl Phys Rev, 2019, 6: 011310

    Article  Google Scholar 

  10. Murphy SV, Atala A. Nat Biotechnol, 2014, 32: 773–785

    Article  CAS  PubMed  Google Scholar 

  11. Jungst T, Smolan W, Schacht K, Scheibel T, Groll J. Chem Rev, 2016, 116: 1496–1539

    Article  CAS  PubMed  Google Scholar 

  12. Bedell ML, Navara AM, Du Y, Zhang S, Mikos AG. Chem Rev, 2020, 120: 10744–10792

    Article  CAS  PubMed  Google Scholar 

  13. Chen WH, Chen QW, Chen Q, Cui C, Duan S, Kang Y, Liu Y, Liu Y, Muhammad W, Shao S, Tang C, Wang J, Wang L, Xiong MH, Yin L, Zhang K, Zhang Z, Zhen X, Feng J, Gao C, Gu Z, He C, Ji J, Jiang X, Liu W, Liu Z, Peng H, Shen Y, Shi L, Sun X, Wang H, Wang J, Xiao H, Xu FJ, Zhong Z, Zhang XZ, Chen X. Sci China Chem, 2022, 65: 1010–1075

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Karsdal MA, Nielsen SH, Leeming DJ, Langholm LL, Nielsen MJ, Manon-Jensen T, Siebuhr A, Gudmann NS, Rønnow S, Sand JM, Daniels SJ, Mortensen JH, Schuppan D. Adv Drug Deliver Rev, 2017, 121: 43–56

    Article  CAS  Google Scholar 

  15. Bielajew BJ, Hu JC, Athanasiou KA. Nat Rev Mater, 2020, 5: 730–747

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Wang Y, Yuan J, Zhao Y, Wang L, Guo L, Feng L, Cui J, Dong S, Wan S, Liu W, Hoffmann H, Tieu K, Hao J. CCS Chem, 2021, 4: 2102–2114

    Article  Google Scholar 

  17. Frantz C, Stewart KM, Weaver VM. J Cell Sci, 2010, 123: 4195–4200

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Rong Y, Zhang Z, He C, Chen X. Sci China Chem, 2020, 63: 1100–1111

    Article  CAS  Google Scholar 

  19. Yang Q, Lv X, Gao B, Ji Y, Xu F. Adv Appl Mech, 2021, 54: 285–318

    Article  Google Scholar 

  20. Olegovich Osidak E, Igorevich Kozhukhov V, Sergeevna Osidak M, Petrovich Domogatskiy S. Int J Bioprint, 2020, 6: 270

    Article  Google Scholar 

  21. Yu R, Li Z, Pan G, Guo B. Sci China Chem, 2022, 65: 2238–2251

    Article  CAS  Google Scholar 

  22. Gu L, Shan T, Ma Y, Tay FR, Niu L. Trends Biotechnol, 2019, 37: 464–491

    Article  CAS  PubMed  Google Scholar 

  23. Tanzer ML. Science, 1973, 180: 561–566

    Article  CAS  PubMed  Google Scholar 

  24. Sorushanova A, Delgado LM, Wu Z, Shologu N, Kshirsagar A, Raghunath R, Mullen AM, Bayon Y, Pandit A, Raghunath M, Zeugolis DI. Adv Mater, 2019, 31: 1801651

    Article  Google Scholar 

  25. Duarte Campos DF, Blaeser A, Korsten A, Neuss S, Jäkel J, Vogt M, Fischer H. Tissue Eng Part A, 2015, 21: 740–756

    Article  CAS  PubMed  Google Scholar 

  26. Atala A. Chem Rev, 2020, 120: 10545–10546

    Article  CAS  Google Scholar 

  27. Zhao X, Song W, Liu S, Ren L. Sci China Chem, 2016, 59: 1548–1553

    Article  CAS  Google Scholar 

  28. Lee JM, Suen SKQ, Ng WL, Ma WC, Yeong WY. Macromol Biosci, 2021, 21: 2000280

    Article  CAS  Google Scholar 

  29. Zhong L, Qu Y, Shi K, Chu B, Lei M, Huang K, Gu Y, Qian Z. Sci China Chem, 2018, 61: 1553–1567

    Article  CAS  Google Scholar 

  30. Nerger BA, Brun PT, Nelson CM. Soft Matter, 2019, 15: 5728–5738

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Stratesteffen H, Köpf M, Kreimendahl F, Blaeser A, Jockenhoevel S, Fischer H. Biofabrication, 2017, 9: 045002

    Article  PubMed  Google Scholar 

  32. Hull SM, Lindsay CD, Brunel LG, Shiwarski DJ, Tashman JW, Roth JG, Myung D, Feinberg AW, Heilshorn SC. Adv Funct Mater, 2021, 31: 2007983

    Article  CAS  PubMed  Google Scholar 

  33. Szklanny AA, Machour M, Redenski I, Chochola V, Goldfracht I, Kaplan B, Epshtein M, Simaan Yameen H, Merdler U, Feinberg A, Seliktar D, Korin N, Jaroš J, Levenberg S. Adv Mater, 2021, 33: 2102661

    Article  CAS  Google Scholar 

  34. Guo K, Wang H, Li S, Zhang H, Li S, Zhu H, Yang Z, Zhang L, Chang P, Zheng X. ACS Appl Mater Interfaces, 2021, 13: 7037–7050

    Article  CAS  PubMed  Google Scholar 

  35. Lee A, Hudson AR, Shiwarski DJ, Tashman JW, Hinton TJ, Yerneni S, Bliley JM, Campbell PG, Feinberg AW. Science, 2019, 365: 482–487

    Article  CAS  PubMed  Google Scholar 

  36. Hull SM, Brunel LG, Heilshorn SC. Adv Mater, 2022, 34: 2103691

    Article  CAS  Google Scholar 

  37. Ouyang L, Highley CB, Sun W, Burdick JA. Adv Mater, 2017, 29: 1604983

    Article  Google Scholar 

  38. Ding S, Hülsey MJ, An H, He Q, Asakura H, Gao M, Hasegawa J, Tanaka T, Yan N. CCS Chem, 2021, 3: 1814–1822

    Article  CAS  Google Scholar 

  39. Long JX, Li XH, Wang LF, Zhang N. Sci China Chem, 2012, 55: 1500–1508

    Article  CAS  Google Scholar 

  40. Wang B, Qin L, Mu T, Xue Z, Gao G. Chem Rev, 2017, 117: 7113–7131

    Article  CAS  PubMed  Google Scholar 

  41. Mahmood H, Moniruzzaman M, Yusup S, Welton T. Green Chem, 2017, 19: 2051–2075

    Article  CAS  Google Scholar 

  42. Wang H, Gurau G, Rogers RD. Chem Soc Rev, 2012, 41: 1519–1537

    Article  CAS  PubMed  Google Scholar 

  43. Meng Z, Zheng X, Tang K, Liu J, Ma Z, Zhao Q. Int J Biol Macromolecules, 2012, 51: 440–448

    Article  CAS  Google Scholar 

  44. Iqbal B, Muhammad N, Jamal A, Ahmad P, Khan ZUH, Rahim A, Khan AS, Gonfa G, Iqbal J, Rehman IU. J Mol Liquids, 2017, 243: 720–725

    Article  CAS  Google Scholar 

  45. Wang J, Wei L, Ma Y, Li K, Li M, Yu Y, Wang L, Qiu H. Carbohyd Polym, 2013, 98: 736–743

    Article  CAS  Google Scholar 

  46. Zhao H, Xu J, Yuan H, Zhang E, Dai N, Gao Z, Huang Y, Lv F, Liu L, Gu Q, Wang S. Mater Horiz, 2022, 9: 342–349

    Article  CAS  PubMed  Google Scholar 

  47. Zhao H, Xu J, Zhang E, Qi R, Huang Y, Lv F, Liu L, Gu Q, Wang S. ACS Appl Mater Interfaces, 2021, 13: 25759–25770

    Article  CAS  PubMed  Google Scholar 

  48. Liu X, Wang X, Zhang L, Sun L, Wang H, Zhao H, Zhang Z, Liu W, Huang Y, Ji S, Zhang J, Li K, Song B, Li C, Zhang H, Li S, Wang S, Zheng X, Gu Q. Adv Healthcare Mater, 2021, 10: 2101405

    Article  CAS  Google Scholar 

  49. Mehta A, Rao JR, Fathima NN. Colloids Surfs B-Biointerfaces, 2014, 117: 376–382

    Article  CAS  Google Scholar 

  50. Valot L, Martinez J, Mehdi A, Subra G. Chem Soc Rev, 2019, 48: 4049–4086

    Article  CAS  PubMed  Google Scholar 

  51. Oosterlaken BM, Vena MP, With G. Adv Mater, 2021, 33: 2004418

    Article  CAS  Google Scholar 

  52. Suehiro T, Kojima C, Tsumura S, Harada A, Kono K. Biopolymers, 2010, 93: 640–648

    Article  CAS  PubMed  Google Scholar 

  53. Liu W, Heinrich MA, Zhou Y, Akpek A, Hu N, Liu X, Guan X, Zhong Z, Jin X, Khademhosseini A, Zhang YS. Adv Healthcare Mater, 2017, 6: 1601451

    Article  Google Scholar 

  54. Ouyang L, Yao R, Zhao Y, Sun W. Biofabrication, 2016, 8: 035020

    Article  PubMed  Google Scholar 

  55. Li H, Tan C, Li L. Mater Des, 2018, 159: 20–38

    Article  CAS  Google Scholar 

  56. Unagolla JM, Jayasuriya AC. Appl Mater Today, 2020, 18: 100479

    Article  PubMed  Google Scholar 

  57. Bernal W, Jalan R, Quaglia A, Simpson K, Wendon J, Burroughs A. Lancet, 2015, 386: 1576–1587

    Article  PubMed  Google Scholar 

  58. Fisher RA. Nat Rev Gastroenterol Hepatol, 2017, 14: 373–382

    Article  PubMed  Google Scholar 

  59. Bogdanos DP, Gao B, Gershwin ME. Compr Physiol, 2013, 3: 567–598

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

This work was supported by the Strategic Priority Research Program of the Chinese Academy of Sciences (XDA16020804, XDA16020802) and the National Natural Science Foundation of China (22021002, 22022705). We are grateful to the research group of Prof. Lijian Hui for the help with HUVEC and PHH cells.

Author information

Authors and Affiliations

Authors

Corresponding authors

Correspondence to Yiming Huang, Qi Gu or Shu Wang.

Additional information

Conflict of interest

The authors declare no conflict of interest.

Supporting information

The supporting information is available online at http://chem.scichina.com and http://link.springer.com/journal/11426. The supporting materials are published as submitted, without typesetting or editing. The responsibility for scientific accuracy and content remains entirely with the authors.

Supporting Information

11426_2022_1472_MOESM1_ESM.pdf

Synthesis of easily-processable collagen bio-inks using ionic liquid for 3D bioprinted liver tissue models with branched vascular networks

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Gao, Z., Liu, X., Zhao, H. et al. Synthesis of easily-processable collagen bio-inks using ionic liquid for 3D bioprinted liver tissue models with branched vascular networks. Sci. China Chem. 66, 1489–1499 (2023). https://doi.org/10.1007/s11426-022-1472-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11426-022-1472-6

Navigation