— What methods of repairing peripheral nerves exist today?
— The gold standard is autotransplantation, the most common method of restoring nerve fibers and therefore sensory and motor activity. The disadvantage is that the operation requires a donor site from which we “remove” the nerve.
—Where is it usually cut?
— Most of the time, we remove the sural nerve: It is removed, the necessary part of the nerve is cut and implanted in the required place. Doctors choose such an area to minimize damage to the functions of the donor nerve.
The main problem here is that we do not always have a donor site, and the size and structure of the sural nerve may not be suitable.
The good thing about the autoneural insert is that we use the patient’s own tissue, which means it will take root well. But on the downside, there may not be enough material or it may not fit some parameters. In addition, a double operation needs to be performed: first we cut off a piece of the nerve and then sew it to the desired place.
— Is there another method to repair nerves?
— If the situation allows, the damaged nerve is stitched end to end. This method can be applied if the lost part of the nerve is small. In such a nerve connection, additional tension may occur due to the ties between the nerve endings.
If the nerve is damaged to a significant extent, direct end-to-end suture without tension is not possible, which negatively affects the regeneration of the nerve – therefore, in such cases, grafts of various origins in the form of guide tubes are used. channels – channels.
— So you grow nerves in a test tube and then transplant them? Or are you creating some kind of artificial neuron analogue?
— We use hollow pipes. They can be obtained in the form of micro- and nanofiber-based tubes or films. The film is then wrapped around the nerve. We insert guide fillers into the cavity of the tube along the growth of nerve fibers.
If we consider the natural structure of the nervous tissue, axons (processes of the nerve cell – “socialbites.ca”) grow in a certain direction (from the proximal end to the distal), and when an injury occurs, special “Strands”, which are a natural channel for regeneration axons and direct the regenerating axons in the required direction is created.
Using this principle, filled tubes directed along the growth of axons were obtained.
The guiding structures in the cavity of the tube help the nerve heal, accelerating it and increasing the degree of healing.
—What fillers are usually used in such tubes?
— Gels, threads and fibers obtained from natural and synthetic materials are generally used as fillers. For example, natural polymers: collagen, gelatin, hyaluronic acid. Synthetic absorbable (absorbable in the body) polymers: polylactide, caprolactone, polyglycolide.
We use filler in the form of fibers based on chitosan and chitin nanofibrils. These are natural absorbable polymers. And most importantly, chitooligosaccharide, the product of chitosan degradation, promotes the restoration of nerve fibers. That’s why we chose chitosan.
— Is it possible to somehow use stem cells as a filler to repair axons?
– Yes. This is the next stage of our work – in addition to physical fillers use biochemical fillers in the form of Schwann cells (auxiliary cells of nerve tissue formed along the axons of peripheral nerve fibers) mesenchymal stem cells. Incorporate them into the structure of physical fillers and create a natural nerve structure.
— Will stem cells turn into nerves?
“We’re talking about helping the person regenerate their own tissue. Tissues will repair themselves, and fillers will imitate the natural structure and create a microenvironment suitable for restoration.
– Usually small damages are repaired using tubes – no more than three centimeters. Your evolution allows you to repair major damage. Are there any restrictions, for example, can a damage of five or ten centimeters be repaired?
— To begin with, our goal is to exceed three centimeters. Naturally, there are limitations on the amount of recovery, but I cannot say exactly what they are, longer studies are needed for this.
The limitations of hollow tube repair size are that irregularity increases as the axon grows; they don’t just regenerate in the forward directionbut due to fillers directed along the growth of the axon. The latter maintains its growth direction longer. The filler acts as a guide for the nerve, telling it where to grow. And the axon grows in the right direction.
— How many millimeters of nerve can grow per day with this approach?
— I can’t say that yet, our research continues. But it’s certainly much faster than using hollow tubes with no filler.
-Can you really repair a completely severed nerve?
– Yes. The use of tubes involves restoring the integrity of the nerve by connecting the ends of the tube to its ends.
This was exactly the research model. We “cut” the sciatic nerve of laboratory animals, creating a specific diastasis (defect) and replacing the defect with a filled tubular implant.
Laboratory animals lost motor activity, which was restored after a certain period of time.
— So you’ve created a clear cut, and if the nerve breaks unevenly, can it still be repaired?
“For example, if a person has an accident in real life, it is not clear what the nervous disorder is. As a rule, the nerve loses its functionality due to damage to a completely incomprehensible situation. In such cases, the nerve is “cut” and then the damaged ends are tied.
— Will it be possible in the future, for example, to sew a person’s head in this way and connect all the nerves?
“This is now how they connect body parts together, either through anastomosis or using an otoneural appendage. These tubes are being developed to make it easier for us in the future to connect nerves with a large gap and avoid tissue deficiency.
I don’t know about the head. I cannot predict such processes, but this concerns not only nerves, but also many organs and tissues.
But maybe someday in the future this will be possible, but not only such technologies will be used for this.
— How different are the approaches to repairing central and peripheral system nerves?
— Completely different technologies are used. In the central nervous system, nerve impulses are transmitted differently, the cells are of different nature, so our approach cannot be transferred to the treatment of damage to the central nervous system.
— Besides introducing stem cells, how do you plan to develop the technology?
— We started experimenting with a bioprinter. Using a bioprinter, we will be able to print guides (fillers) along with the cells. The use of a bioprinter will speed up and simplify the material creation process.
But for now we are printing them without cells. We are experimenting to understand how best to apply the material.
— What other research are you conducting?
— I am also conducting research on the development of implants for bone tissue restoration, including cranioplasty. This is a procedure to repair the bones of the skull.
Let me give you an example about children. In adults, the defect is usually replaced with nonabsorbable materials such as titanium or polymers. However, since the child’s body grows and the listed materials do not dissolve, it is impossible to use such materials in children’s plastic surgery. Therefore, we need absorbable materials that will melt as bone tissue grows. I am currently interested in creating such composite materials.
— What substances do you use for this?
— Such implants must be durable but also absorbable. And this can be achieved by producing composites, that is, by combining two components (a filler in the form of chitosan fabric and a matrix based on polylactide or polycaprolactone). The strength of such composites is comparable to the strength of bone tissue. Bone tissue continues to bear the load and heal, and our material is absorbed over time and replaced by natural bone tissue.
— At what stage of testing are both of your developments? When will both bone implants and nerve restoration tubes be used in the clinic?
“In both cases, we are testing on small laboratory animals. To use the listed materials in clinical practice, a series of non-rapid studies are required. But hopefully we will get there.”