Research ArticleBIOENGINEERING

Magnetic levitational bioassembly of 3D tissue construct in space

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Science Advances  15 Jul 2020:
Vol. 6, no. 29, eaba4174
DOI: 10.1126/sciadv.aba4174
  • Fig. 1 The schematic illustration of the space experiment.

    (A) Cuvettes filled with chondrospheres in thermoreversible nonadhesive hydrogel, culture medium with paramagnetic gadobutrol, and fixative solution (formalin). (B) Main stages of experiment performed on the ISS: activation of cuvettes by cooling down to 15°C, magnetic fabrication of 3D tissue constructs at 37°C, followed by fixation. (C) Transportation of cuvettes back to Earth. Photo credit: Vladislav A. Parfenov and Frederico DAS Pereira, Laboratory for Biotechnological Research “3D Bioprinting Solutions”, Moscow, Russia.

  • Fig. 2 Scientific equipment of space experiment consisting of magnetic bioassembler Bioprinter Organ.Aut and hermetic cuvettes.

    (A) Cross section of magnetic bioassembler (1, magnets; 2, power sources; 3, light source; 4, one of the six cuvette ports). (B) Installation of the cuvette in the magnetic bioassembler. (C) Magnetic bioassembler and cuvettes. (D) Cross section of the cuvette (1, buttons-pistons for the injection of a nutrient medium and a clamp; 2, pistons of the secondary safety circuit; 3, volume for lock; 4, volume for the nutrient medium; 5, valve for the nutrient medium; 6, piston valve for the retainer; 7, volume for chondrospheres and thermoreversible hydrogel). (E) Cross section of cuvette inserted into magnetic bioassembler. (F) Russian cosmonaut Oleg Kononenko with the magnetic bioassembler and cuvettes. Photo credit: Vladislav A. Parfenov and Stanislav V. Petrov, Laboratory for Biotechnological Research “3D Bioprinting Solutions”, Moscow, Russia.

  • Fig. 3 Simulation of the magnetic field and kinetics of tissue spheroid assembly.

    (A) System of magnets installed into magnetic bioassembler. (B) Magnetic field generated by system of magnets. (C) Modeling of construct assembly process. (D) Modeled shape of the construct after assembly. (E) Kinetics of the construct assembly as a function of gadobutrol concentrations and temperature.

  • Fig. 4 Evaluation of biofabrication medium toxicity and rheological parameters.

    (A) Chondrosphere after 72-hour incubation in Mebiol gel. (B) Chondrosphere after 72-hour incubation in culture medium (control) (Live/Dead assay, living cells are stained green). (C) Quantitative assessment of viability of chondrospheres after 72-hour incubation in Mebiol gel and culture medium by using the CellTiter-Glo Kit. (D) Time-curve of intersphere angles for pairs of chondrospheres during the fusion. (E) Distribution of diameters of 2-day-old chondrospheres. (F) Roundness of 2-day-old chondrospheres. (G) Chondrospheres without or after exposure to 10 mM and 50 mM gadobutrol for 24 hours; toluidine blue staining. (H) TEM images of cells within chondrospheres without or after exposure to 10 mM and 50 mM gadobutrol. Some of the representative data are shown. Photo credit: Elizaveta Koudan, Laboratory for Biotechnological Research “3D Bioprinting Solutions”, Moscow, Russia.

  • Fig. 5 Morphological studies of 3D tissue construct obtained by magnetic levitation in space.

    (A) Time-lapse photographs of the construct assembly inside the magnetic bioassembler in space. (B) Computer simulation of chondrosphere fusion into 3D construct using “Surface Evolver” software. (C) Real sequential steps of construct bioassembly in space; snapshots from time-lapse video recording. (D) Macrophotography of assembled 3D construct returned to Earth. (E) Histology [hematoxylin and eosin (HE) staining] and immunohistochemistry [proliferation marker Ki-67 and apoptosis marker caspase-3 (Casp-3)] of 3D tissue construct assembled in space experiment. Photo credit: Kenn Brakke, Susquehanna University, Selinsgrove, PA, USA; Elizaveta Koudan, Laboratory for Biotechnological Research “3D Bioprinting Solutions”, Moscow, Russia.

Supplementary Materials

  • Supplementary Materials

    Magnetic levitational bioassembly of 3D tissue construct in space

    Vladislav A. Parfenov, Yusef D. Khesuani, Stanislav V. Petrov, Pavel A. Karalkin, Elizaveta V. Koudan, Elizaveta K. Nezhurina, Frederico DAS Pereira, Alisa A. Krokhmal, Anna A. Gryadunova, Elena A. Bulanova, Igor V. Vakhrushev, Igor I. Babichenko, Vladimir Kasyanov, Oleg F. Petrov, Mikhail M. Vasiliev, Kenn Brakke, Sergei I. Belousov, Timofei E. Grigoriev, Egor O. Osidak, Ekaterina I. Rossiyskaya, Ludmila B. Buravkova, Oleg D. Kononenko, Utkan Demirci, Vladimir A. Mironov

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