Russian Scientists Have Summed Up The Results Of An Experiment On Printing With Live Cells In Space
Scientists from Russia, Latvia, and the United States published an article in Science Advances describing an experiment on printing cell constructs using a magnetic bioprinter, which took place on the ISS in 2018. Analysis of the obtained samples, conducted on Earth, showed that printing allows you to create constructs with connected cells and high survival rates.
3D printing has long been used in research to create artificial analogs of organs from a solution with real cells of the appropriate type. While ready-to-transplant organs are not printed on them, but primitive prototypes can already be created. Besides, they can be used to create tissue constructs to study the influence of external conditions on cells. In particular, even though space stations with scientific equipment have been flying in orbit for decades, there is still little data on the impact of weightlessness and increased radiation on living organisms, and space 3D printers could become a convenient tool for conducting biomedical research.
But classic 3D printing is based on the layer-by-layer application of a substance, and therefore uses gravity to hold the layers until they are frozen. Layer-by-layer printing can be implemented in space by increasing the viscosity and adhesion of the printing material, which in the case of biological precursor hydrogels is often impossible, or by using a centrifuge or other device to simulate gravity, but this unnecessarily complicates an already complex design.
Russian scientists and engineers from 3D Bioprinting Solutions created the Organ bioprinter in 2018. Auth " for space conditions, which uses not layer-by-layer printing, but magnetic pushing of cells into the center of the printing area. To be more precise, the printer does not work with individual cells, but with their sets, which are prepared on the Ground. To do this, the cells (in this study, chondrocytes were used-cells of cartilage tissue) together with a supporting solution-culture are placed in spherical vessels and allowed to connect, forming an extracellular matrix. As a result, scientists obtained spheres with an average diameter of 300 micrometers.
Spheres with chondrocytes are placed in large combined cuvettes together with hydrogel, which is converted to Sol below 21 degrees Celsius, and higher — to gel. Into another vessel of the cuvette is placed in formaldehyde for fixation of the obtained samples before sending it to the Ground. Also, it contains gadobutrol, a paramagnetic agent that is usually used as a contrast agent in MRI. All cuvettes are loaded into the printer and magnets of complex shape (together they form a hollow cylinder with round cutouts on the sides) push paramagnetic particles into the center of the working area of the cuvette, and together with them, they are sent to the center and spheres of chondrocytes. After the spheres are assembled into a single structure, the cuvettes are kept at a temperature of 37 degrees Celsius for two days and fixed with formalin.
Originally " Organ.AVT " was sent to the ISS on the Soyuz MS-10 spacecraft, but an accident occurred during the flight, so the printer was delivered to the station during the next mission on December 3, 2018, and on the 5th the cosmonauts began experiments on it. On December 20, the cuvettes with printed constructs were "lowered" to Earth by the Soyuz MS-09 spacecraft, and the experiment materials were passed to scientists for analysis.
Histological examination showed that individual spherical particles were combined into a single construct. Besides, the almost complete absence of marker substances showed that there was almost no apoptosis in the constructs before formalin fixation (it releases the enzyme caspase-3, which scientists almost did not find) and proliferation (this process can be detected by the protein KI-67, but it was also extremely small in the constructs).
The authors concluded that, in general, the method has shown its suitability. However, they note that gadobutrol used for collecting spherical particles is toxic, and its concentration will need to be reduced in future studies. They also plan to technically modify the process by adding ultrasonic emitters that will complement magnets as driving force creators for spheres. They plan to add emitters to the cuvettes without the need to modify the printer, which remained on the ISS and is ready for new research.
Recently, Belgium, China, and the United States have experimentally demonstrated the ability to print biological structures through existing tissues. To do this, precursors are introduced into the tissue, and then they are polymerized under the influence of radiation.