A report from the Laboratory of Biophysics-Tissue Bioengineering in Bordeaux. Join us for a behind the scenes look at 3D printing in the health domain.

Has the dream of bioprinting become reality? Yes, partially. Researchers from BioPrint in Bordeaux – the new Accelerator of Technological Research (ART) – have found a way to deposit cells, layer by layer, according to a three-dimensional organization programmed to mimic that of native tissue as closely as possible. Their tools? Bioprinters assisted by the three major bioprinting technologies: laser, inkjet and micro-extrusion.

  • L'équipe de l'ART BioPrint
    The ART team (from l. to r.): Hugo de Oliveira, ART Scientific Coordinator and biomaterials, inkjet and extrusion printing specialist, Davit Hakobyan, expert in laser-assisted bioprinting, Jean-Christophe Fricain, ART Director, and Nathalie Dusserre, Head of Cells and Quality, begin to unpack the new Modulab multimodal printer, which combines laser and inkjet functions.
    © Inserm/Guénet, François
  • Jean-Christophe Fricain
    Jean-Christophe Fricain is Director of both the BioPrint ART and the Tissue Bioengineering Unit (BioTis, Inserm Unit 1026), which is housed on the premises. "We are the only ones to have the three bioprinting technologies at our fingertips," he says. "By combining them, we can obtain a broad range of production – from single cells to organs."
    © Inserm/Guénet, François
  • La bioencre bleue, une suspension cellulaire, est étalée sur la lame "donneuse
    Blue bioink (a cell suspension) is spread onto a "donor" slide. Then Davit Hakobyan places it, bioink face down, in the printer's carousel. A computer-guided laser beam then sweeps the top of the slide in accordance with the computer-designed model.
    © Inserm/Guénet, François
  • n faisceau laser, guidé par l'ordinateur, va ensuite venir balayer le dessus de la lame suivant le modèle conçu à l'aide de l'ordinateur
    Blue bioink (a cell suspension) is spread onto a "donor" slide. Then Davit Hakobyan places it, bioink face down, in the printer's carousel. A computer-guided laser beam then sweeps the top of the slide in accordance with the computer-designed model.
    © Inserm/Guénet, François
  • n faisceau laser, guidé par l'ordinateur, va ensuite venir balayer le dessus de la lame suivant le modèle conçu à l'aide de l'ordinateur
    Blue bioink (a cell suspension) is spread onto a "donor" slide. Then Davit Hakobyan places it, bioink face down, in the printer's carousel. A computer-guided laser beam then sweeps the top of the slide in accordance with the computer-designed model.
    © Inserm/Guénet, François
  • n faisceau laser, guidé par l'ordinateur, va ensuite venir balayer le dessus de la lame suivant le modèle conçu à l'aide de l'ordinateur
    With each pulse of the laser, a nanodroplet detaches from the donor slide (on the left) and is transferred to the collector slide (on the right) to form, here, the Science&Santé logo. Laser technology gives the best resolution and cell viability.
    © Inserm/Guénet, François
  • chambres microfluidiques
    To perfuse printed tissue, one approach is to produce microfluidic chambers (lozenge-shaped) in a gel. The purpose? To enable the necessary culture medium to circulate through the bioprinted structures.
    © Inserm/Guénet, François
  •  Le tissu imprimé contenant des cellules endothéliales est placé dans une chambre microfluidique (forme de losange)
    The printed tissue containing endothelial cells is placed in the chamber. This is then connected to a dynamic perfusion system enabling the maturation of a capillary network within the tissue.
    © Inserm/Guénet, François
  • Chercheuse observant des cellules marquées avec un gène de fluorescence vert.
    To observe the evolution of the bioprinted cells, they must have first been marked with a green fluorescence gene, for example. Nathalie Dusserre checks that this is the case for these glioblastoma (brain tumor) cells.
    © Inserm/Guénet, François
  • A l'écran, des cellules endothéliales bioimprimées expriment un gène de fluorescence apparaissant en rouge et forment des réseaux ressemblant à des capillaires.
    On the screen, the endothelial cells, which express another fluorescence gene, appear in red, and form networks resembling capillaries.
    © Inserm/Guénet, François
  • Les têtes d'impression de l'imprimante sont constituées de microseringues qui permettent de délivrer des biomatériaux contenant des cellules vivantes, toujours selon une organisation programmée par ordinateur
    Combining the large volumes offered by microextrusion and the precision of inkjet is the advantage of this platform. The printer heads are made up of microsyringes that deliver living cell-containing biomaterials, always according to a computer-programmed organization.
    © Inserm/Guénet, François
  • Grâce aux données acquises par IRM d'un cerveau, la bioimprimante peut imprimer un modèle en 3D reproduisant fidèlement la structure initiale.
    Thanks to data acquired by brain MRI, the machine can print a 3D model which faithfully reproduces the initial structure. In the future, this approach could enable the tailor-made printing of tissues for regenerative medicine applications.
    © Inserm/Guénet, François

However, the 3D-printed "tissue" will evolve over time, adding a fourth dimension. For this to occur, it must be nourished and oxygenated. A major limitation to the printing of organs therefore remains the creation of a vascular network to enable total tissue perfusion. Nevertheless, bioprinted cell structures – and simplified organ models – already offer researchers the possibility to test different cell organizations and the effects of radiotherapy or those of medicines.

Inaugurated on October 12, 2017, the primary mission of the ART is to speed up the dissemination of bioprinting technologies throughout the entire Inserm scientific community and apply the knowledge of this multidisciplinary team to various domains (tissue engineering, oncology, pharmacology, etc.) to facilitate the development of innovative research projects in each of its units. Join us for a visit!

Find the report in issue 38 of Science&Santé magazine (in French)