Scientists of the Institute of Cytology and Genetics of the SB RAS, with the participation of students from Novosibirsk State University, have developed an effective method for obtaining tissue engineering designs whose properties are maximally close to physiological ones. Bioprostheses created on the basis of this technology will be able to replace the vessels to a person, who needs transplantation. Development of biologists allows to avoid negative consequences: reduces the risk of inflammation, thrombosis and other immunopathological processes leading to a repeated circulatory deficit.
Vascular surgery is faced with the problem of obtaining small-diameter vessel replacements. The use of blood vessels from the patient is often impossible due to medical indications, and synthetic materials have some physical defects. Tissue engineering provides an opportunity to solve this problem by creating a cell-filled vascular graft. Scientists sel ect not only the sources of cells that model the natural structure of the vessel but also materials suitable for their settlement.
Novosibirsk biologists have developed a method for obtaining tissue engineering designs based on membranes from polycaprolactone and chitosan, inhabited by endothelial and smooth muscle cells of human cardiac explants. The combination of selected cells and materials is necessary to solve the issues of strength, longevity, and physiology of the transplant.
— To develop tissue engineering designs, we used endothelial (lining blood vessels) and smooth muscle (which create a vascular tone) cells of the postoperative human myocardial material, — says participant of the study, a student of the Faculty of Natural Sciences Anna Smirnova, who works in the laboratory of the epigenetics of the development of Institute of Cytology and Genetics of the SB RAS under the guidance of Candidate of Biological Sciences Irina Zakharova — The technology for obtaining these cells was previously developed in our laboratory of the epigenetics of the development of Institute of Cytology and Genetics of the SB RAS (the laboratory head is Doctor of Biological Sciences, Professor Suren Zakian). The settlement of vascular prostheses by these cells will increase the life of the transplant due to their ability to produce an intercellular matrix.
Scientists-developers assume that in this way the risk of inflammation, thrombosis and immunopathological processes, which leads to a repeated deficiency of blood circulation by occluding the lumen of the vessels, will decrease.
In the course of experiments, scientists have shown that human cells, after settling on such membranes retain their functional properties. Also, the researchers calculated the optimal ratio of components for more effective cell proliferation on the surface of the material.
Investigation of tissue engineering structures from a mixture of chitosan and polycaprolactone has been conducted so far only in vitro. However, according to its results, we can now say that the method of obtaining cell-populated tissue engineering designs based on a mixture of polycaprolactone and chitosan can be the basis for the development of functional grafts of small diameter vessels with properties as close as possible to physiological ones. Biologists suggest that the human transplant can be populated by the cells of the patient himself, which does not cause rejection and immune reaction.
Researchers at the laboratory of epigenetics of Institute of Cytology and Genetics of the SB RAS have conducted experiments using the developed settlement technology in vivo in a mouse model. In these experiments, they have used frames made of synthetic polycaprolactone material developed by colleagues at the Laboratory of Molecular Medicine of the Institute of Chemical Biology and Fundamental Medicine of the SB RAS (head of the laboratory — candidate of biological sciences Pavel Laktionov).
These scaffolds were pre-populated with cells of human cardiac explants, obtained fr om the waste postoperative material of the myocardium of the outlet part of the right ventricle. Post-graduate student of the Siberian Federal Biomedical Research Center named after E.N. Meshalkin, a staff member of the Center for Vascular and Hybrid Surgery Saay Shoran (head of the Center - Doctor of Medical Sciences, Professor Andrei Karpenko) has conducted implantation of such cell-populated tissue engineering constructions in the aorta of mice on the basis of the «SPF-vivarium».
— 44 mice were operated, which were divided into two groups (control - with unoccupied polycaprolactone patches, and experimental - with populated). I took part in the experiment, — explains Anna Smirnova. — The animals were observed for 24 weeks. Studies with ultrasound and MRI have confirmed that after implantation the aorta remains passable throughout the entire experiment period, pulsatile blood flow is stored in the bioprosthesis. To confirm the preservation of cells after transplantation, scientists have performed a histological analysis at the experimental control points (2, 4, 12, 24 weeks after the operation), the images were examined with a confocal microscope. In non-cellular prostheses, a specialized endothelial and smooth muscle layer is being not formed, which can subsequently lead to stenosis and blockage of blood vessels. Cell-populated tissue engineering prosthetics create the necessary functional layers of cells and are well integrated into surrounding tissues.
Thus, scientists have shown that cell-populated tissue engineering designs have an advantage over unsettled ones, which is especially important for the development of small-diameter vessel replacements.