Commercialization of regenerative medicine
How to make an "apartment" for a cage
We are talking about the restoration of damaged tissues with the help of submicron fibers and the processes of their renewal. Actually, all approaches to regeneration consist either in its activation or inhibition – up to the replacement of entire organs. Andrey Khomenko, a researcher at MIPT, spoke about research in the field of regenerative medicine and how to create an artificial vessel.
Khomenko starts with a simple one: "Organs and tissues are cells on some kind of framework. The frames are completely different depending on the fabric, but they are necessary – they perform a supporting function. Just swimming in a liquid environment is "bad" for cells. And in order for the cells to feel good – it doesn't matter if it's the future artificial skin, kidneys or liver, we have to make these skeletons for them. They are called cellular matrices. There are quite a lot of technologies for the production of cell matrices today."
For example, scientists use a kind of porous structure as an "apartment" for cells, in which the pore size approximately corresponds to the size of cells. According to Khomenko, such a structure can be biodegradable – over time, the cells will destroy the "edible" framework and form their own.
Biopolymers are well suited for the role of biodegradable material for cell matrices – both artificial (synthesized) and natural origin. The next stage is to make a suitable frame from a bar or biopolymer granules. One of the methods to do this is called electrospinning. Using this technology, a ready-made frame consisting of micro- and nanofibers of polymer is obtained. Depending on the substrate (flat or cylindrical), the resulting matrix will find its use as a frame for artificial skin or a blood vessel.
The functions and properties of the frame are inextricably linked with the future organ, which is planned to grow on this frame. For some cylindrical artificial organs, in addition to the general requirements, one more thing must be observed – the frame must contain annular non-biodegradable inserts that provide mechanical strength. For example, this is required by an artificial trachea – a new project of the NBIC Center of the Kurchatov Institute, the Laboratory of Regenerative Medicine of MIPT and one of the most famous transplantologists Paolo Macchiarini.
The direction of regenerative medicine is actively developing all over the world. A few months ago, the world's first artificial trachea transplant was performed at the Karolinska University Hospital in Stockholm (Sweden). Paolo Macchiarini operated on a 36-year-old man with tracheal cancer – this diagnosis is characterized by high mortality. Tracheal transplantation, before the appearance of its synthetic analogue, had many disadvantages: first of all, these are limitations associated with a shortage of donor organs of the appropriate size. Now such an operation has become more accessible, it is possible to practically eliminate the risk of rejection – the grown frame is covered with stem cells of the patient himself.
"Now we are actively working on creating matrices for growing artificial vessels and tracheas," Khomenko tells what the essence of the joint project is. – There are a lot of formations in the human body that have a hollow, cylindrical shape. Sometimes they need to be replaced because of some disease. What is needed for this? First, you need to make a frame - a hollow cylindrical tube made of biopolymer. Electrospinning makes this matrix very easy. A sufficiently flat substrate, which is used for preliminary experiments, is replaced with a drum whose diameter corresponds to the diameter of the vessel, and we begin to dust the polymer fiber on it, simultaneously rotating it. Then we just take out the drum and we get a tube - a ready-made frame."
The technology itself is relatively simple. It does not require expensive equipment, but it is very important to choose the parameters of the experiment. Naturally, electrospinning is not a panacea and not a universal technology. For example, frameworks for artificial organs, such as the liver or kidneys, are generally very difficult to obtain by electrospinning – they are voluminous. Sponges, or bioprinting, are better suited here. But the walls of the vessels are thin, they are easier to make.
Electrospinning is the pulling of fibers from a polymer solution or melt by applying a high DC voltage. The technology has been around for more than 70 years. The Soviet Union was a pioneer in the invention of such a method for producing nanofibers. At first, electrospinning was not used in biotechnology, but was used to make filters, especially for the nuclear industry. A good example is the Petal respirator, which was used to eliminate the consequences of the Chernobyl accident. In the USSR, all work on electrospinning was classified, and only closer to the 80s came the understanding that using this technology it was possible to make a cell matrix or a frame for an artificial organ and tissue. But then the Soviet Union collapsed, and these works were frozen for a long time.
"The second discovery of electrospinning was experienced in the 90s in America. Professor Darrell Reneker rediscovered the method. He knew nothing about Soviet developments, started from scratch and realized the great potential of the technology. He also started with non–biodegradable large-tonnage polymers, and then switched to biodegradable ones," Andrey clarifies.
The process of pulling fibers looks something like this: there is a device that looks like an ordinary medical syringe, with a thin needle. Only instead of medicine, it is filled with a polymer solution. The solvent for each polymer is different. For example, alcohol is a bad solvent for sugar, and water is a good one.
"We work with many biopolymers," Khomenko continues. – Let's say if it is chitosan, then the solvent for it will be concentrated vinegar: 90% acetic acid and 10% water. We add the polymer there, mix it and get a homogeneous, homogeneous solution, which we pour into the feeding device – a syringe, and start spinning."
The solution is squeezed onto a metal substrate at a very high voltage – tens of kilovolts. One contact of the battery is connected to the syringe, and the other to the plate. The whole method is based on a simple physical postulate – the electric charges of the same name repel each other, and the opposite ones attract. Such a huge strain is needed to create a significant repulsive force. Due to it, the trickle begins to stretch, increase in length. And in diameter, respectively, decrease. If you choose all the conditions correctly, then in flight all the solvent will have time to evaporate and only a polymer thread will remain, a dry fiber will fall on the substrate.
"The diameter of the fiber can vary from 10 to 1000 nanometers, that is, up to one micrometer. And the speed of fiber formation (how much fiber will fall to the surface per unit of time) is crazy, reaching several kilometers per second. Due to multiple interlacing and inter–fiber interaction, a good non-woven material is obtained," says Khomenko. A clear analogy for non–woven fiber is cotton wool or napkin, which also consist of tangled, numerous fibers.
After the rediscovery of eletrospinning by American colleagues, Russian scientists expanded the scope of the technology - a regenerative fabric made of nanofibre was created, which showed positive results during the tests. At Saratov State University named after N.G. Chernyshevsky, a material better known as "second skin" was obtained from submicron chitosan fibers. Non-woven fiber and patches made from it have antibacterial and wound healing properties. The "second skin" resolves itself as the wound heals and quickly stops bleeding. It looks like a cotton fabric, although it feels much softer.
Tests have shown that on the 14th day, a 3rd degree burn is practically cured if synthetic skin is applied to it. SSU scientists plan to complete the tests by the summer of 2012, which means that the development will not appear on sale until 2013.
Portal "Eternal youth" http://vechnayamolodost.ru24.04.2012