AccScience Publishing / IJB / Volume 9 / Issue 1 / DOI: 10.18063/ijb.v9i1.633

Fabrication of lumen-forming colorectal cancer organoids using a newly designed laminin-derived bioink

Rosario Pérez-Pedroza1,2† Fatimah Al-Jalih1,2† Jiayi Xu1,2† Manola Moretti1,2 Giuseppina R. Briola1 Charlotte A. E. Hauser1,2*
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1 Laboratory for Nanomedicine, BESE, King Abdullah University of Science and Technology (KAUST), Thuwal 23955-6900, Kingdom of Saudi Arabia
2 Computational Bioscience Research Center, King Abdullah University of Science and Technology (KAUST), Thuwal 23955-6900, Kingdom of Saudi Arabia
Submitted: 21 July 2022 | Accepted: 5 August 2022 | Published: 4 November 2022
(This article belongs to the Special Issue Related to 3D printing technology and materials)
© 2022 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International License ( )

Three-dimensional (3D) bioprinting systems, which are the prominent tools for biofabrication, should evolve around the cutting-edge technologies of tissue engineering. This is the case with organoid technology, which requires a plethora of new materials to evolve, including extracellular matrices with specific mechanical and biochemical properties. For a bioprinting system to facilitate organoid growth, it must be able to recreate an organ-like environment within the 3D construct. In this study, a well-established, self-assembling peptide system was employed to generate a laminin-like bioink to provide signals of cell adhesion and lumen formation in cancer stem cells. One bioink formulation led to the formation of lumen with outperforming characteristics, which showed good stability of the printed construct. 

Biofunctional bioink
Self-assembling peptide

1. Tuveson D, Clevers H, 2019, Cancer modeling meets human organoid technology. Science, 364(6444): 952–955.

2. Sharick JT, Jeffery JJ, Karim MR, et al., 2019, Cellular metabolic heterogeneity in vivo is recapitulated in tumor organoids. Neoplasia, 21(6): 615–626.

3. Luo C, Lancaster MA, Castanon R, et al., 2016, Cerebral organoids recapitulate epigenomic signatures of the human fetal brain. Cell Rep, 17(12): 3369–3384.

4. van de Wetering M, Francies HE, Francis JM, et al., 2015, Prospective derivation of a living organoid biobank of colorectal cancer patients. Cell, 161(4): 933–945.

5. Fair KL, Colquhoun J, Hannan NRF, 2018, Intestinal organoids for modelling intestinal development and disease. Philos Trans R Soc Lond B Biol Sci, 373(1750): 20170217.

6. Clevers H, Tuveson DA, 2019, Organoid models for cancer research. Annu Rev Cancer Biol, 3(3): 223–234.

7. Sato T, Clevers H, 2015, SnapShot: Growing organoids from stem cells. Cell, 161(7): 1700–1700 e1.

8. Sato T, Stange DE, Ferrante M, et al., 2011, Long-term expansion of epithelial organoids from human colon, adenoma, adenocarcinoma, and Barrett’s epithelium. Gastroenterology, 141(5): 1762–1772.

9. Bernal PN, Bouwmeester M, Madrid-Wolff J, et al., 2022, Volumetric bioprinting of organoids and optically tuned hydrogels to build liver-like metabolic biofactories. Adv Mater, 34(15): e2110054.

10. Skylar-Scott MA, Huang JY, Lu A, et al., 2022, Orthogonally induced differentiation of stem cells for the programmatic patterning of vascularized organoids and bioprinted tissues. Nat Biomed Eng, 6: 449–462.

11. Aisenbrey EA, Murphy WL, 2020, Synthetic alternatives to Matrigel. Nat Rev Mater, 5(7): 539–551.

12. Gjorevski N, Sachs N, Manfrin A, et al., 2016, Designer matrices for intestinal stem cell and organoid culture. Nature, 539(7630): 560–564.

13. Pérez-Pedroza R, Ávila-Ramírez A, Khan Z, et al., 2021, Supramolecular biopolymers for tissue engineering. Adv Polym Tech, 2021: 23.

14. Susapto HH, Alhattab D, Abdelrahman S, et al., 2021, Ultrashort peptide bioinks support automated printing of large-scale constructs assuring long-term survival of printed tissue constructs. Nano Lett, 21(7): 2719–2729.

15. Loo Y, Chan YS, Szczerbinska I, et al., 2019, A chemically well-defined, self-assembling 3D substrate for long-term culture of human pluripotent stem cells. ACS Appl Bio Mater, 2(4): 1406–1412.

16. Chan KH, Xue B, Robinson RC, et al., 2017, Systematic moiety variations of ultrashort peptides produce profound effects on self-assembly, nanostructure formation, hydrogelation, and phase transition. Sci Rep, 7(1): 12897.

17. Lakshmanan A, Cheong DW, Accardo A, et al., 2013, Aliphatic peptides show similar self-assembly to amyloid core sequences, challenging the importance of aromatic interactions in amyloidosis. Proc Natl Acad Sci, 110(2): 519–524.

18. Hauser CA, Deng R, Mishra A, et al., 2011, Natural tri- to hexapeptides self-assemble in water to amyloid beta-type fiber aggregates by unexpected alpha-helical intermediate structures. Proc Natl Acad Sci U S A, 108(4): 1361–1366.

19. Sordat I, Bosman FT, Dorta G, et al., 1998, Differential expression of laminin-5 subunits and integrin receptors in human colorectal neoplasia. J Pathol, 185(1): 44–52. 185:1<44::AID-PATH46>3.0.CO;2-A

20. Sordat I, Rousselle P, Chaubert P, et al., 2000, Tumor cell budding and laminin-5 expression in colorectal carcinoma can be modulated by the tissue micro-environment. Int J Cancer, 88(5): 708–717. https://doi . org/10.1002/1097-0215(20001201) 88:5<708::Aid-Ijc5>3.3.Co;2-A

21. Sun Y, Li W, Wu X, et al., 2016, Functional self-assembling peptide nanofiber hydrogels designed for nerve degeneration. ACS Appl Mater Interfaces, 8(3): 2348–2359.

22. Wu Y, Zheng Q, Du J, et al., 2006, Self-assembled IKVAV peptide nanofibers promote adherence of PC12 cells. J Huazhong Univ Sci Technol, 26(5): 594–596.

23. Xu H, Shao Z, Wu Y, et al., 2009, Effects of self-assembled IKVAV peptide nanofibers on olfactory ensheathing cells. Chin J Biotechnol, 25(2): 292–298.

24. Buzzelli JN, Ouaret D, Brown G, et al., 2018, Colorectal cancer liver metastases organoids retain characteristics of original tumor and acquire chemotherapy resistance. Stem Cell Res, 27: 109–120.

25. Cioce V, Castronovo V, Shmookler BM, et al., 1991, Increased expression of the laminin receptor in human colon cancer. J Natl Cancer Inst, 83(1): 29–36.

26. Seow WY, Salgado G, Lane EB, et al., 2016, Transparent crosslinked ultrashort peptide hydrogel dressing with high shape-fidelity accelerates healing of full-thickness excision wounds. Sci Rep, 6(1): 32670.

27. Fauchere J-L, Charton M, Kier LB, et al., 1988, Amino acid side chain parameters for correlation studies in biology and pharmacology. Int J Pept Prot Res, 32(4): 269–278.

28. Chaudhuri O, Gu L, Klumpers D, et al., 2016, Hydrogels with tunable stress relaxation regulate stem cell fate and activity. Nat Mater, 15(3): 326–334.

29. Haugh MG, Vaughan TJ, Madl CM, et al., 2018, Investigating the interplay between substrate stiffness and ligand chemistry in directing mesenchymal stem cell differentiation within 3D macro-porous substrates. Biomaterials, 171: 23–33.

30. Humphries MJ, 2009, Cell Adhesion Assays, Extracellular Matrix Protocols, Springer, New York City, 203–210.

31. Arthur A, Zannettino A, Gronthos S, 2009, The therapeutic applications of multipotential mesenchymal/stromal stem cells in skeletal tissue repair. J Cell Physiol, 218(2): 237–245.

32. Hersel U, Dahmen C, Kessler H, 2003, RGD modified polymers: Biomaterials for stimulated cell adhesion and beyond. Biomaterials, 24(24): 4385–4415.

33. Kabsch W, Sander C, 1983, Dictionary of protein secondary structure: Pattern recognition of hydrogen-bonded and geometrical features. Biopolymers, 22(12): 2577–2637.

34. Lakshmanan A, Hauser CA, 2011, Ultrasmall peptides self-assemble into diverse nanostructures: Morphological evaluation and potential implications. Int J Mol Sci, 12(9): 5736–5746.

35. Kikkawa Y, Hozumi K, Katagiri F, et al., 2013, Laminin-111-derived peptides and cancer. Cell Adhes Migr, 7(1): 150–159.

36. Kreidberg JA, 2000, Functions of α3β1 integrin. Curr Opin

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International Journal of Bioprinting, Electronic ISSN: 2424-8002 Print ISSN: 2424-7723, Published by AccScience Publishing