3D bioprinting in Russia: new horizons

Skolkovo told about laser printing with living cells

Evgenia Efimova, Vesti 

The third scientific conference on bioprinting and biofacturing, held jointly by the 3D Bioprinting Solutions Biotechnological Research Laboratory and the Skolkovo Innovation Center, has already taken place in Moscow. Professor at the University of Hanover. Leibniz, Boris Chichkov, Head of the Nanotechnology Department at the Hanover Laser Center, and Professor Vladimir Mironov, Scientific Director of the 3D Bioprinting Solutions Biotechnological Research Laboratory, spoke about the key technologies used in laser printing with living cells and achievements in this field.

3D bioprinting is a field of regenerative medicine, which also includes cell therapy and tissue engineering.

"Organ bioprinting differs from tissue engineering in that a robotic device is used, that is, the technology is based on robots. Secondly, it is not enough to use a robot, it is necessary to use information technology, that is, each building block is invested according to a digital model," Mironov said.

The basic idea of bioprinting, or bioprinting, is the collection of tissues and organs from conglomerates of cells, like a designer. According to Mironov, biochernils are called tissue spheroids (densely packed aggregates of living cells) capable of self–discharge, and bio-paper is a hydrogel into which "drops" of living matter are embedded. The assembly itself can be carried out on bioprinters. By the way, in 2014 the first domestic 3D bioprinter called FABION was introduced.

What does laser printing of three-dimensional structures have to do with it? "We use a technology called two-photon polymerization. With this technology, you can create real three–dimensional structures," says Chichkov.

Two–photon polymerization is a laser method of manufacturing a three-dimensional structure according to a pre-developed model.

According to Chichkov, in this way you can not just print a three-dimensional structure, but also "structure" it inside. "This allows you to create three–dimensional scaffolds," he says. The word scaffold translates from English as "scaffolding, scaffold", in other words, "scaffold" is a supporting structure.

Note that scaffolds are three–dimensional matrices whose main function is to provide a mechanical framework for cells.

There are already three three-dimensional printing systems in Russia. In particular, one of them is located at the Institute of Laser and Information Technology Problems of the Russian Academy of Sciences (IPLIT RAS).

This technology allows you to create hybrid polymers. "We have developed these materials. They have such a property that if you have created a model in a computer, you can print it into the material. At the same time, there is practically no compression of the structure," says Chichkov. In addition, it is possible to create three-dimensional structures: the size of the element can be less than 100 nanometers.

According to the scientist, one of the most interesting applications for this technology in the coming years may be the creation of so-called organs-on-a-chip. Such a device will help simulate the behavior of an entire human organ (for example, when taking certain medications).

What is necessary for laser printing with living cells? The matrix is a biological basis, which should be identical to the natural one, in other words, consist of a person's own cells. "Cells and bioactive materials are also needed. You can use, for example, a mouse or a human as a bioreactor, where this scaffold can be placed," explains Chichkov.

Let's explain what the process of printing with living cells is. A hydrogel with living cells in it is placed on the upper thin strip of the material. At the bottom there is a substrate on which the printed object will be applied. Under the influence of a laser pulse, the energy-absorbing layer creates a shock wave. It, in turn, transfers biological objects (a drop with cells) to the lower substrate.

But not everything is so simple. "One of the main problems is how to insert blood vessels into the resulting scaffold," says Chichkov.

According to him, scientists are now putting a lot of effort into the development of this direction. Experiments show that sometimes good capillaries are obtained, sometimes not. "Basically, I hope it will be possible," he adds.

The key advantages of laser printing with live cells are that you can work with an arbitrary number of cells and with a material of any viscosity. "This means that you can put a lot of cells in a hydrogel, and we can create a large concentration of cells. The technology guarantees high cell survival: after printing with stem cells, they remain in culture for several days. We observe that the structure remains the same as it was. These stem cells can then be differentiated into cartilage or bone. This technology is compatible with everything you can do with stem cells," notes Chichkov.

According to him, the technology does not affect the cells. "It even has a stimulating effect on cells, but it is quite difficult to prove this experimentally. In any case, everyone agrees with our conclusion that laser printing does not affect cells," he says.

It is also important that lasers allow you to automate the printing process. "All your cars are laser–welded today, it's the same here," the scientist said.

If today, in general, you will not surprise anyone with bioprinting, then the researchers surprised the audience with new projects. So, Chichkov reported about the "seal" by the earth and microorganisms. The fact is that today scientists have cultivated only one percent of the existing microorganisms. The remaining 99% are left out of research. The difficulty lies in the fact that a tiny volume of soil contains a whole universe of microorganisms, it is extremely difficult to study each individual species in this case. But if you grind the earth…

"The fact that we can print small pieces of land on which there are only a few microorganisms allows us to gain access to new types of microorganisms and then cultivate them. And we hope that new antibiotics will be created along the way," says Chichkov.

Mironov was also intrigued by a new project called "fabric gun" (tissue gun). "We decided to create something that never happened. What is Russia known for? The fact that we produce a Kalashnikov assault rifle. And we want to create something that does exactly the opposite – tissue gun. But how it works and what's inside, we won't tell you yet," the scientist intrigued the audience. Another interesting project is related to the problem of baldness. According to Chichkov, in order to grow hair in the skin, cells are needed that "create" the root of the hair. To do this, it is necessary to use "pouches" in which it will be possible to grow hair follicles (follicles). "Such elements were created by Mironov's team. They were called capillinsers (capillinser)," Chichkov said.

According to Mironov, the name "capillinser" is formed from the words "hair" (capillo in Latin) and "insertion" (insertion).

One of the possible technologies for combating baldness will be as follows: "The skin is taken, holes are made with a laser, capilliners with dermos and epidermis cells are inserted there, the hair begins to grow, and the capilliners degrade. After some time, there will be no people on Earth who do not have hair at all," a Russian scientist tells about the new project.

Of course, when laser printing with living cells ceased to be a scientific fantasy and became quite real, the question arose: "Is it possible to print a person and what will it take?". "A person weighing 100 kilograms consists of ten cells to the fourteenth degree. And today's technologies will allow you to print an array of a person in two hours and forty-seven minutes. Of course, it will not be a person in the literal sense of the word, it will just be a cellular conglomerate. But, nevertheless, it is quite real," concluded Chichkov.

Portal "Eternal youth" http://vechnayamolodost.ru 17.02.2015