Aspiration-assisted Freeform Bioprinting of Prefabricated Tissue Spheroids in a Yield-stress Gel

Overview

Journal Commun Phys

Publisher Springer Nature

Date 2020 Nov 30

PMID 33251340

Citations 41

Authors

Bugra Ayan

Nazmiye Celik

Zhifeng Zhang

Kui Zhou

Myoung Hwan Kim

Dishary Banerjee

Yang Wu

Francesco Costanzo

Ibrahim T Ozbolat

Affiliations

Soon will be listed here.

Abstract

Bioprinting of cellular aggregates, such as tissue spheroids, to form three-dimensional (3D) complex-shaped arrangements, has posed a major challenge due to lack of robust, reproducible and practical bioprinting techniques. Here, we demonstrate 3D aspiration-assisted freeform bioprinting of tissue spheroids by precisely positioning them in self-healing yield-stress gels, enabling the self-assembly of spheroids for fabrication of tissues. The presented approach enables the traverse of spheroids directly from the cell media to the gel and freeform positioning of the spheroids on demand. We study the underlying physical mechanism of the approach to elucidate the interactions between the aspirated spheroids and the gel's yield-stress during the transfer of spheroids from cell media to the gel. We further demonstrate the application of the proposed approach in the realization of various freeform shapes and self-assembly of human mesenchymal stem cell spheroids for the construction of cartilage and bone tissues.

Citing Articles

Spheroids from Epithelial and Mesenchymal Cell Phenotypes as Building Blocks in Bioprinting (Review).

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Bioprinting of bespoke islet-specific niches to promote maturation of stem cell-derived islets.

Kim M, Cho S, Cho S, Hwang D, Shim I, Kim S Nat Commun. 2025; 16(1):1430.

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Model construction and clinical therapeutic potential of engineered cardiac organoids for cardiovascular diseases.

Wang Y, Hou Y, Hao T, Garcia-Contreras M, Li G, Cretoiu D Biomater Transl. 2025; 5(4):337-354.

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Engineering the 3D structure of organoids.

Moss S, Bakirci E, Feinberg A Stem Cell Reports. 2024; 20(1):102379.

PMID: 39706178 PMC: 11784486. DOI: 10.1016/j.stemcr.2024.11.009.

Spherical Shell Bioprinting to Produce Uniform Spheroids with Controlled Sizes.

Son K, Kim D, Park S, Kim H, Park M, Kim S J Funct Biomater. 2024; 15(11).

PMID: 39590553 PMC: 11595458. DOI: 10.3390/jfb15110350.

References

Jakab K, Norotte C, Damon B, Marga F, Neagu A, Besch-Williford C . Tissue engineering by self-assembly of cells printed into topologically defined structures. Tissue Eng Part A. 2008; 14(3):413-21. DOI: 10.1089/tea.2007.0173. View

OBryan C, Kabb C, Sumerlin B, Angelini T . Jammed Polyelectrolyte Microgels for 3D Cell Culture Applications: Rheological Behavior with Added Salts. ACS Appl Bio Mater. 2022; 2(4):1509-1517. DOI: 10.1021/acsabm.8b00784. View

Highley C, Song K, Daly A, Burdick J . Jammed Microgel Inks for 3D Printing Applications. Adv Sci (Weinh). 2019; 6(1):1801076. PMC: 6325587. DOI: 10.1002/advs.201801076. View

Miri A, Khalilpour A, Cecen B, Maharjan S, Shin S, Khademhosseini A . Multiscale bioprinting of vascularized models. Biomaterials. 2018; 198:204-216. PMC: 6360139. DOI: 10.1016/j.biomaterials.2018.08.006. View

Shih Y, Tseng K, Lai H, Lin C, Lee O . Matrix stiffness regulation of integrin-mediated mechanotransduction during osteogenic differentiation of human mesenchymal stem cells. J Bone Miner Res. 2010; 26(4):730-8. DOI: 10.1002/jbmr.278. View

Chakrabarti A, Chaudhury M . Direct measurement of the surface tension of a soft elastic hydrogel: exploration of elastocapillary instability in adhesion. Langmuir. 2013; 29(23):6926-35. DOI: 10.1021/la401115j. View

Style R, Hyland C, Boltyanskiy R, Wettlaufer J, Dufresne E . Surface tension and contact with soft elastic solids. Nat Commun. 2013; 4:2728. DOI: 10.1038/ncomms3728. View

Mironov V, Visconti R, Kasyanov V, Forgacs G, Drake C, Markwald R . Organ printing: tissue spheroids as building blocks. Biomaterials. 2009; 30(12):2164-74. PMC: 3773699. DOI: 10.1016/j.biomaterials.2008.12.084. View

Moldovan N, Hibino N, Nakayama K . Principles of the Kenzan Method for Robotic Cell Spheroid-Based Three-Dimensional Bioprinting<sup/>. Tissue Eng Part B Rev. 2016; 23(3):237-244. DOI: 10.1089/ten.TEB.2016.0322. View

10.

Duan B, Yin Z, Hockaday Kang L, Magin R, Butcher J . Active tissue stiffness modulation controls valve interstitial cell phenotype and osteogenic potential in 3D culture. Acta Biomater. 2016; 36:42-54. PMC: 4883663. DOI: 10.1016/j.actbio.2016.03.007. View

11.

Ayan B, Wu Y, Karuppagounder V, Kamal F, Ozbolat I . Aspiration-assisted bioprinting of the osteochondral interface. Sci Rep. 2020; 10(1):13148. PMC: 7403300. DOI: 10.1038/s41598-020-69960-6. View

12.

Pairam E, Le H, Fernandez-Nieves A . Stability of toroidal droplets inside yield stress materials. Phys Rev E Stat Nonlin Soft Matter Phys. 2014; 90(2):021002. DOI: 10.1103/PhysRevE.90.021002. View

13.

McCormack A, Highley C, Leslie N, Melchels F . 3D Printing in Suspension Baths: Keeping the Promises of Bioprinting Afloat. Trends Biotechnol. 2020; 38(6):584-593. DOI: 10.1016/j.tibtech.2019.12.020. View

14.

Heo D, Alioglu M, Wu Y, Ozbolat V, Ayan B, Dey M . 3D Bioprinting of Carbohydrazide-Modified Gelatin into Microparticle-Suspended Oxidized Alginate for the Fabrication of Complex-Shaped Tissue Constructs. ACS Appl Mater Interfaces. 2020; 12(18):20295-20306. DOI: 10.1021/acsami.0c05096. View

15.

Hinton T, Hudson A, Pusch K, Lee A, Feinberg A . 3D Printing PDMS Elastomer in a Hydrophilic Support Bath via Freeform Reversible Embedding. ACS Biomater Sci Eng. 2016; 2(10):1781-1786. PMC: 5059754. DOI: 10.1021/acsbiomaterials.6b00170. View

16.

Mattsson J, Wyss H, Fernandez-Nieves A, Miyazaki K, Hu Z, Reichman D . Soft colloids make strong glasses. Nature. 2009; 462(7269):83-6. DOI: 10.1038/nature08457. View

17.

Gabbanelli S, Drazer G, Koplik J . Lattice Boltzmann method for non-Newtonian (power-law) fluids. Phys Rev E Stat Nonlin Soft Matter Phys. 2005; 72(4 Pt 2):046312. DOI: 10.1103/PhysRevE.72.046312. View

18.

Yu Y, Zhang Y, Martin J, Ozbolat I . Evaluation of cell viability and functionality in vessel-like bioprintable cell-laden tubular channels. J Biomech Eng. 2013; 135(9):91011. PMC: 3708706. DOI: 10.1115/1.4024575. View

19.

Leberfinger A, Dinda S, Wu Y, Koduru S, Ozbolat V, Ravnic D . Bioprinting functional tissues. Acta Biomater. 2019; 95:32-49. PMC: 6625952. DOI: 10.1016/j.actbio.2019.01.009. View

20.

Mironov V, Boland T, Trusk T, Forgacs G, Markwald R . Organ printing: computer-aided jet-based 3D tissue engineering. Trends Biotechnol. 2003; 21(4):157-61. DOI: 10.1016/S0167-7799(03)00033-7. View