“Mixture of the animate and inanimate”. What organs are printed in Russia and when will they be implanted in people?

— What kind of research do you do at NUST MISIS?

We have several directions. We are currently interested in developments in bioprinting, tissue engineering and various implants for both hard and soft tissues.

For example, we made ear implants for people with ear injuries. It was created by bioprinting, that is, by 3D printing with a cellular component. We print the frame necessary for external similarity. It also repeats the biomechanics of elastic cartilage – it has the same flexibility, can help tissues regenerate and is ideally later compensated by new tissue.

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Fedor Senator

From personal archive

The next direction is the development of new bioprinting methods. We work in partnership with the Russian company 3D Bioprinting Solutions. Simply 3D printing is when you apply material layer by layer and that way you can print anything, even a house, even a bone implant. In bioprinting, a cellular component must be present. We want to develop two more new directions.

The first is in situ bioprinting (ie directly in the patient’s body). A person has a skin injury, burn, tissue needs regeneration. To do this, there is a robotic arm that can close such a defect directly on the patient. And the nuance here is that only a conventional printer will print on a smooth, flat surface, but an on-site bioprinter should print on a curved surface, for example, the patient’s stomach.

The robot should have feedback, for example, a person jerked or took a deep breath, then the printer should not accidentally poke it, harm it in some way.

For laboratory animals, this printing method took 20-30 minutes according to the time. Until now, it can only be applied to the skin, because conditionally it is enough to apply five layers, and you already have thin skin. With other organs it will be more difficult.

The second aspect is the use of different physical spaces for printing.

What if we could create an organ from all directions at once, for example, if cells converged into one spot at the same time, as in science fiction movies, to form an organ? This can be done using magnetic pressure, when the cells rise in the air and then begin to aggregate in one place in the form of a future organ.

We are working on that too.

— You mentioned the cellular component. It turns out that these implants can be called “live”?

“Anything that has a cellular component can be called alive. Something is certain to live in such products, either cells or tissue spheroids (these are artificially created balls of cells). Our implants are, very roughly speaking, a combination of animate and inanimate.

We also have other areas, for example bone implants. A separate complex area that we have begun to develop within the framework of the Priority 2030 state program is the area of ​​neuroprosthesis creation for people with spinal cord injury and peripheral nerve damage.

— What are your neuroprostheses, do you have artificial neurons?

“Well, think of a nerve as something elongated like this. And with an injury, that something ruptured, so in technical language we need to make a cylinder like this, a connection that will connect the nerve. This implant has to be electrically conductive, and cells with special protein molecules inside should contain.

For spine surgery, things are more complicated. There it is necessary to create an implant that will regenerate the nerve tissue. It must also be electrically conductive. Its job is to help nerve tissue grow in one direction so that it moves in a specific direction rather than randomly to heal any defect that occurs during spinal cord injury.

These implants are soft plates made of a silicone-like polymer with specially formed grooves through which the growth of nerve tissue can be stimulated.

All this is still in the early stages of development, but ideally we want our implants to be able to fully or at least partially restore motor activity in people with back injuries.

— You talked about the difficulties of pressing organs, what kind of problems do you face?

– Printing complex organs is a long process, and so far there is no one in the world who can technologically make large organs that actually produce something functional, for example.

In order for an organ to function, various processes within it must function correctly. Imperfections are possible during 3D printing, even traditional printing, especially if the object is large. The more defects, the more likely the organ will not work properly.

The second issue concerns the nuances of bioprinting. This is still not very fast when you apply cells layer by layer. If you’re printing a large organ, the process will take several hours (or dozens of hours). In this case, in the absence of special incubation conditions, the lower layers of cells may begin to die due to lack of nutrient flow. There is no vein, it has not yet been created. And because of this, there is a possibility of damaging the bottom printed layers.

Now, for example, it is possible, in principle, to press a part of the heart, a muscle. The nuance is in the functional and large organs. They have not yet been printed.

– Abroad, there are already precedents for the use of printed organs in humans. And when to expect in Russia?

– I can say that the first organs to be placed on a person are bone implants and cartilage and skin pressure. We will start installing these for humans by 2030.

Now we can actively apply our developments in the veterinary field. We already have a lot of cases. For example, four years ago we created a cell-engineered claw for the cat Lapuni. For the last two years we have been manufacturing respiratory stents for dogs with laryngeal collapse.

– You’re talking about printed fabrics, and it looks like they’re no different from living fabrics. This is true?

— When we talk about creating organ equivalents, we often use the concept of biomimetics. That is, a complete similarity in structure, architecture, external geometry and biomechanics should be observed. At the same time, high biocompatibility, bioactivity and functionality should be observed. Ideally, it is quite difficult to repeat everything at once, so it all depends on the place of implantation.

For example, if it is bone prostheses, then architecture and biomechanics are primarily important here. When we talk about soft tissues, there are even more nuances to consider. Ensuring maximum vascularization and germination of blood vessels, incl. Generally, soft tissue implants are bioabsorbable implants, meaning they need to be slowly dissolved and replaced with body tissue.

— You are still dealing with intellectual materials. What is it?

“Materials that can change any of their properties in a controlled manner under the influence of an external factor. For example, the most common are shape memory materials. Respiratory stents for dogs were placed in the larynx in a compressed form, and from the warmth of the dog’s body the implant opened, taking a different, desired shape.

There are materials that react to light, changes in electromagnetic radiation, changes in acidity and humidity. We mainly deal with form change. This is necessary to approach 4D printing. This type of bioprinting involves changing the shape of an already printed product.

This is required for minimally invasive implant placement. But that’s still far from the whole lab and practice level.

— And how is material created for printing?

– There is a task – you need to compensate for the tissue of an organ. First we choose the material. For example, it could be ceramic or some kind of polymer for bones.

Next, we look at whether we need a cellular component. If necessary, is it possible to first print the frame and then fill it with cells. Or if it is a soft organ, it is necessary to immediately press with cells or tissue spheroids. For example, we can take cells, disperse them in a special gel, and then print them with cell gel. Most often, stem cells isolated from the patient’s bone marrow are used.

— How is the field of bioprinting developing in Russia?

– There are very few teams that are seriously interested in this right now, the region is quite young. It will definitely be a breakthrough. Only in Russia there are not so many bioprinters yet. But young people are actively coming to us, scientists are interested in developing this field, so I am sure that bioprinting has a very good future.

What do you mean by “breakthrough”?

– We will gradually move from printing organ samples to the clinic, that is, we will already use them in medicine. As I said, we believe that the first thing that can be done for a person is cartilage (for example, an auricle) and skin pressure. We set the horizon for ourselves somewhere around 2025-2027.

— What tasks do you personally perform for yourself in the context of your scientific activity?

– I don’t really like sci-fi that talks about distant horizons. One of my main goals is to go to the clinic. Another is to create some kind of large functional organ. After all, our center is called “scientific and educational”, so there is another important task – to prepare such students who can participate in the bioprinting of the future. It’s not existing technologies that are in the early stages of development, but technologies that will be ready to immediately print organs such as the pancreas or heart.