Body.Avt

The main articles are:

• 3D printing in medicine
• Organ cultivation (Bioprinting, bioprinting)

Organ.Auth is a 3D bioprinter created by the 3D Bioprinting Solutions biotechnology research laboratory for growing tissues and subsequently organs in a space laboratory. It can also be used to study the influence of space factors on living objects during long-range flights: skin samples grown in space from real cells, internal organs, etc.

Principle of operation

The work of the bioprinter is based on magnetic levitation technology, which allows it to effectively create living tissues and microorganics in zero gravity conditions. The name "3D bioprinter" is quite conventional: the device has no moving parts, and the process of growing the material does not occur additive, that is, layered, but using the "formative" principle, when the sample grows in a strong magnetic field under microgravity conditions. According to its developers, this is one of the most advanced methods for October 2018, which is just beginning to be used in technology. At the same time, the use of technology in space conditions will save it from a significant drawback - the need to use high concentrations of toxic paramagnetics (gadolinium salts), which are needed for experiments on Earth. Ultimately, this will increase the survival rate of the cellular structures created.

Inside the device are installed GoPro cameras, with which you can observe the progress of the experiment.

Applications

In the future, this technique, according to the manufacturers of the device, can be used to create organs from biomaterials delivered to orbit of specific patients. This method has two obvious advantages at once: there is no need to wait for a donor organ suitable for transplantation to appear, and the issue of engraftment is automatically resolved. Another possible application of the bioprinter is to grow protein food, such as cosmic "mince," which will continue to grow as it is consumed.^[1]

2024: Seal hollow organs in space

On April 12, 2024, Russian researchers from the University of Science and Technology MISIS (NITU MISIS) reported that they had managed to print hollow organs in space for the first time in the world. The work was carried out on board the ISS using the domestic magnetic bioprinter Organ.Avt.

On March 25, 2024, the Soyuz MS-25 launch vehicle delivered to the Russian segment of the ISS containers for the Organ.Auth installation, prepared on Earth by specialists from 3D Bioprinting Solutions and NUST MISIS. The cuvettes contained metal-polymer plates containing a cell monolayer on the surface. Under the influence of a magnetic field and temperature, these plates formed tubular structures.

source = MISIS

The uniqueness of the study lies in the use of the thermoactivable effect of shape memory, due to which the plates twist. The applied material returns to its original appearance under the influence of external forces, even if it has been previously deformed. Changes can occur under the influence of various factors such as temperature, light, moisture or magnetic field. At the same time, it is possible to program the material for the desired shape and fixation time.

The work called "Magnetic Biofabrication" was carried out on board the ISS by Russian cosmonaut Oleg Kononenko and the first Belarusian female astronaut Marina Vasilevskaya. The resulting tissue constructs are sent to Earth for comprehensive analysis: scientists will conduct histological and immunohistochemical assessments, as well as investigate the morphology of the structure.

My colleagues and I conducted pre-flight preparation of samples for further filling into the bioprinter, programming a narrow temperature range of exposure: at room temperature, the plates were even, and when they reached 36 degrees in the magnetic field, they folded. To do this in space, also for the first time in the world, is definitely a success, "says Fedor Senatov, director of the Institute of Biomedical Engineering at NUST MISIS.[2]

2020

Start of bone bioprinting experiment

On April 12, 2020, Zdrav.Expert learned that Russian astronauts on the ISS began an experiment to print inorganic components of rat bone tissue. Printing will take several days.

Russian cosmonauts conduct an experiment on bioprinting bone tissue

The obtained samples will be returned to Earth, after which scientists will study them, and in the fall of 2020 they plan to conduct experiments to transplant these samples to rats, said Yousef Hesuani, managing partner of 3D-Bioprinting Solutions, which created the space bioprinter.

Prior to that, experiments on printing various tissues - cartilage, bone, muscle - have already been carried out on a Russian bioprinter in space. This time, the astronauts will have to print only bone tissue for several days. The designers of the experiment are interested in the properties of materials obtained in space, that is, their ability to initiate tissue growth and how well they are suitable as a framework for such growth. In the future, such technology can be used to treat critical fractures, as well as to replace defects in tumors of bone tissue or surrounding soft tissues with metastases to bone. For the first time, such an experiment was conducted in orbit by cosmonaut, Hero of Russia Oleg Kononenko. Here's what he revealed:

During the first session of the experiment, which I performed in December 2018, a tissue-engineering construct of human cartilage (chondrosphere) and rat thyroid was obtained from animal thyroid cells. If we speak strictly scientific language, then in the conditions of weightlessness by the method of magnetic levitation assembly, formative biofabrication of tissue engineering structures was successfully carried out. The study has an undeniable world priority for Russia, since previously similar ones were not carried out by anyone in conditions of zero gravity.

The practical application of this technology is the study of cosmic radiation. Cosmic radiation negatively affects the human body, especially when flying outside the protective magnetosphere of the Earth. Bioprinting technology makes it possible to create radiation-sensitive so-called sentinel organs as models for studying radiation effects. This knowledge will be required when performing long-distance flights, when planning the construction of lunar bases and the creation of planetary settlements.

On April 12, 2020, Russian cosmonauts Anatoly Ivanishin, Ivan Wagner and Oleg Skripochka, as well as Americans Chris Cassidy, Andrew Morgan and Jessica Meir are on the ISS. Ivanishin and Wagner arrived from Cassidy on April 9 on the Soyuz MS-16 and brought the materials necessary for the experiment. Oleg Skripochka will return to Earth with Morgan and Meir at Soyuz MS-15 and bring the resulting tissues for study^[3].

Plans for 3D printing of rat bone tissues

On March 4, 2020, Zdrav.Expert learned that from April 10, 2020, the crew of the International Space Station will begin experiments on 3D printing of bone tissues for subsequent recrystallization and transplantation to rats. The research uses the magnetic bioprinter Organ.Auth, authored by the Russian company 3D Bioprinting Solutions.

Bioprinter "Organ.Auth"

The equipment was delivered aboard the ISS in December 2018. As of March 2020, experiments were carried out on 3D printing of organic constructs using mouse thyroid cells, human cartilage tissues, muscle and connective tissues of rabbit, fish and beef, and even E. coli.

The experiment on 3D printing of bone tissues will be performed by cosmonauts Anatoly Ivanishin and Ivan Wagner, who will go into orbit on April 9, 2020 on the Soyuz MS-16 spacecraft. 3D Bioprinting Solutions actively attracts foreign companies and research institutions to research: scientists from the USA and Israel took part in previous experiments on 3D printing with muscle and connective tissues, providing organic samples^[4].

2019

Plans for the development of a magnetic-acoustic ditch

On December 7, 2019, it became known that 3D Bioprinting Solutions plans to develop a magnetic-acoustic cuvette (removable containers where microorganics are printed - approx. TASS) for a bioprinter during 2020. This was announced by Dmitry Fadin, director of strategic development and innovation at Invitro (one of the laboratory's investors).

As of December 2019, work is underway to create a new type of ditch. We plan to complete development in 2020, noted Fadin

Earlier, Youssef Hesuani, managing partner of the 3D Bioprinting Solutions biotechnology research laboratory, said that the company has plans to complicate the equipment. According to him, in an improved ditch, acoustic waves will be superimposed on magnetic waves in order to obtain a more complex geometric shape of printed organs. The laboratory cooperates with the United Rocket and Space Corporation.

The Organ.Auth bioprinter was delivered to the ISS at the end of 2018. At the same time, the first bioprinter went to the ISS on October 10, 2018 on the Soyuz MS-10 spacecraft. However, it was not possible to deliver it to the station due to the accident of the launch vehicle. Then, on December 3, 2018, a bioprinter-backup arrived on the Soyuz MS-11 on the ISS, which were used for ground testing and training of astronauts. On it, Russian cosmonaut Oleg Kononenko, for the first time in the world, put an experiment on the cultivation of human cartilage tissue and the thyroid gland of a mouse in space. The obtained samples were delivered to Earth and transferred to specialists for study.

Cosmonaut Roskosmos Oleg Kononenko conducted an experiment in December 2018 on bioprinting the tissues of the thyroid gland and human cartilage in orbit. The experiment was considered successful. In September 2019, an experiment was conducted on the ISS to print meat from cow, rabbit and fish cells. It lasted seven days, the size of the meat samples received was several millimeters. For December 2019, research on the results of experiments continues on Earth^[5]

Growing bone tissue fragment on the ISS

On November 25, 2019, Zdrav.Expert learned that Russian cosmonauts working on the International Space Station created fragments of an artificial bone structure with tissues from calcium-phosphate ceramics using the Organ.Aut bioprinter.

Russian cosmonaut Oleg Kononenko working with the bioprinter 'Organ.Auth' on the ISS

Microstructure of synthetic material for tissue engineering/ © 'Izvestia', Institute of Metallurgy and Materials Science, Russian Academy of Sciences

{{quote 'author = explained the head of the Institute of Metallurgy and Materials Science. A.A. Baykov RAS Vladimir Komlev'We use biocompatible materials based on calcium-phosphate ceramics, which in their composition are almost identical to the inorganic component of real bone: it consists of a similar set of substances. Special development properties are achieved due to the self-organization of the material at physiological temperatures, }}

The work of the bioprinter "Organ.Auth," created by the biotechnology research laboratory 3D Bioprinting Solutions for growing tissues and organs, differs from the work of an ordinary 3D printer: it "prints" not on layers, but on the principle of "sculpting snowball," that is, the object is created from all sides at the same time.

The astronauts managed to form a fragment of spheroid bone tissue from ceramic particles. After that, the fragments began to interact with each other, forming stable chemical bonds. Then, living constituting cells were uniformly distributed over the surface of the spheroid, which subsequently formed a tissue-engineering structure, narrated by Comlev

Tissue Engineering Structure of Biocompatible Calcium Phosphate Ceramics and Scaffolding Cells/Izvestia ©, Institute of Metallurgy and Materials Science, Russian Academy of Sciences

The first batch of material for the study was sent to the ISS in August 2019, and in early October, samples created on board the station returned to Earth. As of November 25, 2019, scientists are working with them.

Experiments on growing tissues in orbit will continue. They plan to add stem cells with human DNA to the ceramic composition - with their help, the structure will carry the patient's biological information, which will improve the engraftability of implants in the body. In addition, scientists plan to gradually complicate the shape of the grown bones, bringing it closer to the characteristics of the biological original^[6] to^[7] on interplanetary^[8].

Subsequently, we are going to complicate the geometry of the products being created, for which we will add sound radiation to the basic effect of the printer, which will work together with magnetic waves. This will make it possible to create tubular and branching objects that in their shape will correspond to the bones and vessels of man, noted co-founder of 3D Bioprinting Solutions Youssef Hesuani

As scientists explain, an experiment on growing tissues in space will one day allow you to quickly create bone tissue - for example, in emergency situations when one of the astronauts is injured - and conduct operations right in zero gravity^[9].

2018

Printing 12 organs and tissues in space

On December 21, 2018, it became known that with the help of a domestic 3D bioprinter installed on the ISS from 3D Bioprinting Solutions, the astronauts had already printed six human cartilages and six mouse thyroid glands. This was written by RIA Novosti with reference to the message 3D Bioprinting Solutions.

While on the ISS and other hypothetical space stations, astronauts cannot receive medical assistance for serious damage sustained at the station or during spacewalks. To help solve this problem, scientists from several countries are conducting experiments on printing human organs and connective tissues under microgravity conditions on the ISS. In the future, these experiments are expected to allow the repair of damaged tissues, muscles and organs in the event of their damage in orbit or in space.

In the near future, the Invitro company will deliver the created tissue and organ samples to Earth and conduct their histological studies. It is assumed that the first results of the experiment will be published in 2019.

The Russian experiment on printing organs in orbit began on December 4. Then a mouse thyroid construct was printed on a 3D printer.^[10]

Russia was the first in the world to print live fabrics in space

The medical company Invitro and the biotechnology laboratory 3D Bioprinting Solutions on December 12, 2018 informed Zdrav.Expert about the successful completion of the first stage of the space experiment Magnetic 3D Bioprinter. On December 3, Organaut was delivered to the ISS on the Soyuz MS-11 manned spacecraft. Test cosmonaut Oleg Kononenko first in orbit with the help of a Russian bioprinter printed human cartilage tissue and the rodent's thyroid gland.

The joint project "Invitro," 3D Bioprinting Solutions and the state corporation Roscosmos with the support of the Skolkovo Foundation became the first ever experiment in orbit, initiated by a Russian private company. 700 pages of detailed justification were required from scientists to take at least the first step towards the implementation of the project, and for a year and a half the technological preparation of the experiment continued, taking into account all the conditions of the ISS. In addition to technical and scientific innovations, a number of new organizational approaches were applied in the experiment, which in the future can be translated into other companies working with the public sector in the segment of space technologies and innovations.

According to Andrei Divaev, head of R&D at the business systems department of the state corporation Roscosmos, partnership with a private company in this format has become a "unique experience for the state corporation" that will help in further projects with commercial companies.

Youssef Hesuani, managing partner of 3D Bioprinting Solutions, recalled for his part that biological material printed in space will return to Earth on December 20 on the Soyuz MS-09 spacecraft.

In the first half of 2019, 3D Bioprinting Solutions plans to take stock of the space experiment and publish the results. An American space experiment using a bioprinter is scheduled for February, but the Russian team has already become the first, the company emphasized.

It is very important for us that Russian scientists work in Russia. Our task is to involve talented youth in the scientific process. We want to create something new, and we want young people in Russia to have a decent education, desire and opportunity to work. The bioprinting industry is just the intersection where real technological revolutions are taking place, "said Alexander Ostrovsky, CEO of Invitro, founder of 3D Bioprinting Solutions.

As you know, the bioprinter was already on board the Soyuz MS-10 spacecraft on October 11, 2018, whose crew returned to Earth 20 minutes after the emergency. The device was lowered to the ground in the household compartment and significantly suffered from overloads. As soon as possible, his understudy was prepared and re-training of the crew was organized. According to Yousef Hesuani, even after an emergency descent, only the body of the device is damaged, the device itself is serviceable and may well serve science, its fragments will be transferred for exposition to the Museum of Cosmonautics at VDNKh. Under the skin of the bioprinter is symbolic engraving - 50 names of scientists, patrons and the entire team, thanks to which the project "Magnetic 3D Bioprinter" became possible.

Operability after falling from a height of about 70 km

On November 16, 2018, information appeared that the Russian space bioprinter Organ.Auth, which did not reach the International Space Station due to the Soyuz MS-10 accident and fell along with the ship's household compartment from an altitude of about 70 kilometers, was damaged, but remained operational.

We studied the fallen equipment. Biomaterial, of course, had no chance to survive. The Organ.Aut bioprinter itself remains in working order in case of serious damage to the external decorative part due to the integrity of the magnets. I am very proud of our team, able to make equipment that remains in working order even when falling from space, "said Youssef Hesuani, managing partner of 3D Bioprinting Solutions, which created the bioprinter. - For comparison: GoPro cameras are smashed to smithereens.

Bioprinter "Organ.Auth" was developed specifically for working in zero gravity. It works with spheroids about a couple of hundred micrometers in diameter, made up of living cells. Since printing must take place in zero gravity, the printer does not push spheroids through the nozzle, but collects them into the center of the printing area using a magnetic field.

Before launch, the device itself and cuvettes with printing material were distributed among different Soyuz modules - the printer was located in the household compartment, and the cuvettes were placed in the descent vehicle. In an accident, in accordance with the logic of the rescue system, the descent vehicle separated from the household compartment and dropped by parachute, the household compartment was not equipped with parachutes and was badly damaged when dropped.

According to Hesuani, his colleagues are preparing another copy of the bioprinter for the launch of the Soyuz, which is due to launch to the ISS on December 3. Russian cosmonaut Oleg Kononenko will conduct experiments with the bioprinter. ^[11]

The death of a bioprinter during the accident of the Soyuz launch vehicle

The first Russian bioprinter designed to create living micro-organs and tissues of space was lost during the Soyuz launch vehicle accident. This was announced on October 12, 2018 by a source in the rocket and space industry, RIA Novosti reports. According to the information provided, the device was in the household compartment, which separated from the descent capsule of the Soyuz MS-10 ship and burned out with all its contents when dropped in the atmosphere.

According to Yousef Hesuani, managing partner of the creator of the 3D Bioprinting Solutions apparatus, Organ.Auth was supposed to go to the ISS with the aim of developing bioprinting technologies, testing the latest drugs and assessing the impact of radiation on cell development. The bioprinter was supposed to conduct the first ever experiment on printing biological objects in space.

In particular, it was assumed that the ISS crew during the experiment will try to grow small samples of the rodent's thyroid gland and human cartilage tissue. The biological material was sent along with a printer in a special gel, which changes to a liquid state when the temperature changes, creating a nutrient medium.

According to 3D Bioprinting Solutions, the growing process takes about a day. Then you need to add a fixing material to the ditch. Biological objects can be stored in this state for several weeks, before departure to Earth.

The Soyuz-FG Raketa carrier with the Soyuz MS-10 manned spacecraft, which launched on October 11 from the cosmodrome, Baikonur crashed at the 165th second of the flight. A rescue capsule with cosmonaut "" Roskosmos Alexei Ovchinin and astronaut NASA Nick Hague landed safely near Zhezkazgan in, the Kazakhstan crew was not injured.

The executive director of Roscosmos for manned programs, Sergei Krikalev, said on October 12 that the direct cause of the Soyuz-FG rocket accident was a collision of elements during the separation of the first and second stages of the carrier.^[12]

"Organ.Auth" will go to the ISS

The equipment for the first Russian commercial experiment "Magnetic 3D Bioprinter," which is being prepared in close cooperation with specialists from Roscosmos, RSC Energia and TsNIImash, is planned to be sent to the ISS, 3D Bioprinting Solutions reported on October 10, 2018 . The launch of the spacecraft with a printer on the ISS is scheduled for October 11.

Our task was to assess the technical feasibility of this experiment, to ensure control over the preparation of the necessary equipment - the printer itself and the cuvette for biomaterial - for the conditions of delivery to orbit and the results obtained - back. In addition, the specialists of RSC Energia organized the entire set of necessary certification procedures for this kind of equipment in accordance with the international safety rules in force on the ISS, "said Dmitry Surin, deputy head of the scientific and technical center of RSC Energia.

In total, two sets of equipment were manufactured. One - a prototype - has already passed all the necessary ground-based autonomous tests at Energia and the Institute of Biomedical Problems of the Russian Academy of Sciences. The second - a simulator sample - was used in the process of training crew members: the main (Alexey Ovchinin) and backup (Oleg Kononenko). Training at the CPC with the participation of specialists from 3D Bioprinting Solutions and RSC Energia has already been completed, all comments and proposals of the astronauts will be taken into account.

The third - flight - a sample of equipment for the experiment "Magnetic 3D Bioprinter" is preparing to be sent to the ISS. As noted, the greatest difficulties among scientists were caused not by the adaptation of the printing process, but by the development of a special ditch for the delivery of tissue spheroids to the ISS, since previously no one sent such materials to the station in a ready form. In total, it is planned to send 12 cuvettes with cellular spheroids of mice and humans into space. The cuvettes will be filled with chemicals necessary for the fabrication and subsequent fixation of the grown material, as well as biosimilars, from which the final structure will be built. According to the results of the first stage of the experiment, scientists plan to obtain samples measuring 2-3 mm. It is planned to be human cartilaginous tissue and rodent thyroid.

It was decided to make the outer skin of the device from the ZEDEX composite material acceptable for space flights, which has high wear resistance. At the same time, classic stainless steel was chosen for the main body. The developers managed to make the most compact design, the dimensions of which in length, width and height are 25, 15 and 19 cm, respectively. Thanks to this, it will be easily placed in a cell incubator already operating at the station.^[13]

Biological samples are very sensitive to storage time, so the experiment must be started immediately after the arrival of astronauts and equipment on the ISS. The results of the experiment should return to Earth in the winter of 2018. The biosimilars who have arrived from orbit will be met by a specialist from RSC Energia, who will ensure their prompt delivery to biologists - applicants for the experiment (representatives of the 3D Bioprinting Solutions biotechnology research laboratory).

It is assumed that in the future the bioprinter can be used both by the applicants of the experiment and by third-party scientific teams. His assigned service life is five years.

2016

Start of the project "Magnetic 3D Bioprinter"

According to information, 3D Bioprinting Solutions the Magnetic 3D Bioprinter project was launched in 2016, when an agreement was signed with (RSC Energia the state corporation) Roskosmos to conduct an experiment on the Russian segment. MICROSEC It was important for scientists to analyze how cosmic microgravity affects the effectiveness of the process of creating living tissues and organ constructs.

Working prototype

A working prototype of the bioprinter appeared in the fall of 2016, after which its tests began, which included trial work in zero gravity.

To simulate cosmic conditions within the Earth's laboratory, scientists used the super-powerful magnetic installation of the University of Nijmegen (Netherlands), with the help of which the microgravity effect was created (the induction of the magnets used in the experiment is 19 tesla). To finance this test, 3D Bioprinting Solutions received a grant from the European Union. As a result of the test, the developers saw how the printer would behave on the ISS, and made all the necessary settings.

As part of the bioprinter trials, we used three main approaches, "said Yusef Hesuani, co-founder and managing partner of 3D Bioprinting Solutions. - The first of them is testing the device in terrestrial conditions with the use of weak magnets at high concentrations of gadolinium salts to form a magnetic trap. Then we reduced the concentration of these substances by two orders of magnitude and created the necessary microgravity using supermagnets (this is our experiment in the Netherlands). The third and most important stage will be held already in the Russian segment of the ISS in conditions of natural weightlessness with a minimum concentration of paramagnets and with weak magnets.

2014: First Sample

In the summer of 2014, 3D Bioprinting Solutions specialists under the guidance of Professor Vladimir Mironov created the first domestic bioprinter.

Notes