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The future of bioprinting is out of this world at 3D Bioprinting Solutions in Moscow

We met Co-founder Yusef Khesuani and learned about more exciting projects

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Ever since we began covering them as the first Russian bioprinting company, 3D Bioprinting Solutions, or 3dbio for short, came across as more focused on raising awareness on bioprinting by conducting high profile experiments than on exploring commercial applications for the future of bioprinting. Visiting the company’s lab in Moscow, and speaking with Co-founder Yusef Khesuani, we learned that it may be exactly the opposite: maybe we are not talking about 3dbio nearly as much as we should.

In fact, that may all be changing now with some more announcements coming up in the next few weeks. One of the main issues limiting 3dbio’s visibility in Western Europe and North America may be related to the fact that they are based in Russia. Due to generalized lack of awareness of Russian matters in the West, the way for 3dbio to get some well-deserved recognition has been to do things that are – quite literally – out of this world: building Russia’s first bioprinter (Fabion) in 2014, bioprinting and implanting a rodent thyroid gland in 2015, developing a bioprinter based on magnetic levitation and finally sending (not once but twice) said bioprinter, aptly named Organ.aut, to print in space on the ISS. That was in 2018.

Now the time has come for the bioprinting company to “come back down to Earth” and leverage its space-faring experience to venture into more short-term commercially viable businesses, such as bioprinting meat or in-situ bioprinting of tissue grafts. We spoke about these and the bioprinting market’s status in general with Dr. Khesuani.

Born InVitro

3D Bioprinting Solutions was founded by INVITRO, the largest private medical company in Russia, which is why the laboratory is located on one floor of the INVITRO facility in Moscow. The company’s other Co-founders include INVITRO founder Alexander Ostrovsky and VIVAX BIO CEO & CFO (also INVITRO Advisory Committee Member) Yakov Balakhovsky. New York-based VIVAX BIO is actually 3D Bioprinting Solutions’ mother company through a complex structure that sees 3dbio as the core research lab used to fuel ideas for new, bioprinting based, commercial startups.

“We hope that our R&D efforts will serve to create new spinoffs that will work as business startups,” Dr. Khesuani begins. “3dbio is not a classical startup. We are here to set the foundations for science and give direction. Now we are going to launch a new startup next January, focusing on bioprinting artificial (bioficial) meat and based on the successful experiment we conducted printing meat on the ISS, together with Aleph Farms. In this case, we used the muscle cell sources supplied by Aleph Farms and combined them with our bioprinting technologies.”

future of bioprinting

While artificial (or bioficial) meat may be closer to commercialization, the ultimate goal of 3dbio has been to produce human organs from the very beginning. Khesuani points out how bioprinters today are made primarily to “print” scientific papers rather than organs or implantable tissues. “They basically combine different cells, different hydrogels and different geometries. Every different combination of one of these three factors is a basis for a new scientific paper,” he says. Bioprinters are also used for drug discovery by companies like Organovo, another firm that started with the goal to print organs then moved to drug research. Khesuani believes that “the drug discovery analysis process for bioprinted tissues is still too incomplete to attract big pharma companies.”

From space…

One key difference between 3dbio and other bioprinting companies is that, after the Fabion and Fabion 2 systems, which are based on different types of extrusion, deposition and curing processes, they have now been working on a more volumetric approach for bioprinting in space‘s microgravity environment. While extrusion and deposition systems are considered ideal for “flat”, layered organs, such as cartilage and skin, more complex, “tubular” organs, such as, for example, a urethra, need a more tridimensional approach.

Using the Organ.aut magnetic system and further developing new acoustic means of controlling cellular materials in microgravity, 3dbio’s volumetric technique is able to produce more complex constructs without requiring a scaffold. The bioprinter now on the ISS uses magnetic fields to control the cellular materials. Using microgravity as a co-factor, it implements a scaffold-free, nozzle-free and label-free (no magnetic nanoparticles involved) formative approach. 3dbio researchers also showed off an early version of the acoustic system (in the video above). In theory, one could be used to distribute the material on the X and Y axes while the other could be used to control them along the Z-axis.

future of bioprinting What feels particularly amazing is that, while visiting the 3dbio lab and speaking with Dr. Khesuani, Earth’s orbit, all of a sudden, seems a lot closer. Supplies from 3dbio regularly go up to (and down from) the ISS, in special containers that even have a stamp showing they transited on the ISS (seen in the photo above). In general, all of Moscow seems to have a particularly close relationship with space. When 3dbio approached Roscosmos about bioprinting in space in 2014 their proposal was met with enthusiasm. The project was conducted very rapidly, in spite of the first launch failing. Now laughing about it, Khesuani revealed that the bioprinter that fell back to Earth from a height of about 80,000 meters was actually still functional and will be exhibited at the Space Museum in Moscow in March.

IN the large image, the design of the magnetic bioprinter now on the ISS and, in the photo on the left-hand side of the monitor, Russian cosmonaut Oleg Kononenko visiting 3dbio. Above, an image of the magnetic bioprinter and, on the right, astronaut Oleg Kolonenko, who printed human cartilage tissue and a rodent thyroid gland using the bioprinter in space.

…To in-situ

Another approach to bioprinting that 3dbio is exploring is that of using a multi-axis robot for in-situ contour 3D bioprinting – also considered a type of volumetric 3D printing. “We have also been working with Kuka on using one of their robots to 3D printing tissue grafts directly on the body and we are soon going to announce another startup focusing on this technique,” Khesuani reveals. “We implemented our nozzles on the robotic arm to print directly on skin defects. One key issue that we are approaching is that our system will be able to use computer vision and machine learning algorithms in order to compensate for a living organism’s body” movements while breathing.

Along with the software, 3dbio developed a number of innovations for material handling in order to make the skin graft truly effective These will be officially presented next December 6th, in a joint release with Kuka. The first experiments will be conducted on small size pigs. Some experiments were already successfully conducted on rats, however, Khesuani explained that there is a significant gap between experimenting on small and large animals and an even bigger gap between large animals and humans. “We expect to have the results of the tests for in-situ bioprinting on the pigs sometime next year,” he said.

future of bioprinting
One of the more “standard” nozzled on the Fabion 2 system depositing hydrogel.

Taking a bite out of biomaterials

If bioprinting may still take years to bring real commercial applications, is bioprinted meat any closer? The answer lies in what we mean by meat. Just like industrial applications, to fully leverage the benefits of digital, additive manufacturing we need to completely reinvent food products. That’s one of the reasons why there is so much interest for bioprinting in space, where astronauts and cosmonauts already need to eat very different paste-like food products.

“A lot of people think the goal is to bioprint a steak,” Khesuani explains. “If that is the final objective, then regenerative medicine may actually be closer. What we need to do is imagine new food products based on cellular agriculture. Even snacks such as Mars or Snickers were invented for military purposes in the 50s and 60s. We need to think of food products that do not exist today.”

future of bioprinting
Protein crystals, produced by the Organ.aut bioprinter on the ISS

One of the biggest limits, in food as in medical bioprinting, is the lack of adequate cellular materials. “It’s almost like having Google without having the Internet,” Khesuani says. “We have the bioprinters to surf but we lack the materials to surf on.” For in-situ medical applications, 3dbio developed the Viscoll line of collagen materials, which are suitable for any 3D bioprinter. It is a concentrated sterile solution of highly purified Type 1 collagen which can be used to print three-dimensional scaffolds directly, or blended with cell suspensions to print cell-laden hydrogels. It was designed for the engineering of biocompatible and non-toxic, three-dimensional tissue constructs ideal for tissue engineering and regenerative medicine. A unique feature of the Viscoll hydrogel range is the use of a viscous solution of collagen with a physiological pH value, enabling the addition of living cells or spheroids without neutralization prior to 3D bioprinting. This significantly reduces the time and effort spent on conducting experiments and increases the viability of biological material.

The wide range of collagen concentration allows researches to produce designs with different mechanical densities and rates of bioresorption, depending on their biomedical purpose and the type of cells being used – fibroblasts, multipotent mesenchymal stromal cells, pancreatic islet cells, and so on. The presence of any collagen Types I-V or other ECM proteins (Vitronectin, Fibronectin, Laminin) in the hydrogel determines the specific tissue type of the constructs: skin, bone or cartilage tissue, blood vessels, and parenchyma of internal organs.

Going where no bioprinter has gone before

Selling bioprinters is also a possible commercial business, and several FABION systems are now installed worldwide. Khesuani does not expect this to ever become a core business for 3dbio as operating these machines require engineering experience that is not often found in a scientific laboratory. The systems are generally installed in institutes that partner directly with 3dbio on developing new applications.

future of bioprinting

“We have to be optimistic – Khesuani says -. When we started there were maybe six bioprinting companies all over the world, now there are over 80 including companies, like CELLINK that have a great business model, although different from ours. Our goal was always to print human organs. We need to focus on that, rather than on selling more machines”. He believes that other possible areas of expansion could be the development of medical devices and a new B2S – business to science – segment, where 3dbio could provide scientific results from experiments and help to commercialize them, as they are doing with the bioprinter in space.

One such result, also achieved in space, was growing of protein crystals, another was the development of new materials in space to use in regenerative medicine. Yet another was the production of 3D structures using bacteria, also in space, to study antibiotic resistance. 3dbio continuous to build networks with some of the most prestigious universities in the world and is entering talks with other space agencies such as ESA and JAXA. Next up will be the next generation of magnetic and acoustic bioprinters for volumetric bioassembly, as 3dbio continues to go where no other bioprinting company has ever gone before while building the bioprinting application market here on Earth.

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