Development of Highly Effective Not Calcifying Biomaterials for the Needs of Cardiovascular Surgery

It is known that the main problem of biological substitutes of heart valve or vessel is a pronounced ability of these biomaterials to undergo calcification in the body of the recipient that lead to the early loss of hemodynamic function and repeated time-consuming operations. Because of number of patients with heart valve and blood vessels diseases annually increases not only among older people but also among young people is very important to develop functional, durable and non calcifying alternatives for replacement damaged heart valve and / or vessels for young (under 45 years) patients.

Thus, to date, the use of cell-free / non-immunogenic biological scaffolds of elastic type with a suppressed ability to passive calcification is the most promising and accessible to the population (economic expediency) area of contemporary reconstructive medicine.

In the Laboratory of tissue engineering (ITEB RAS) a hypothesis was suggested that initiation of calcification in transplants occurred because of calcium and phosphates accumulation in mitochondria of the dying cells of the donor (PMID: 16572831). The evidence obtained suggests that under death of artery cells (for instance in the case of ischemia of lower extremities), when for a certain period of time after cell death the mitochondria remain viable, calcification of the vascular wall may also occur by the mechanism described above.

Further, it was noted that the aseptic calcification of the native aortic wall in vivo is observed mainly in the t.adventitia (lipid-rich layer of aortic wall). It has been shown that this type of calcification is carried by migrating recipient cells under the influence of donor matrix lipids (oxLDL, mLDL or mPhospholipids). It has been shown that removal of initiating matrix lipids from the aorta grafts (by acetone-, bile acids-, and others treatment) showed significant reduction of calcification (PMID: 21033364).

On the basis of this hypothesis was developed the Anticalcification treatments (2 patents of RF) for heart valves and blood vessel grafts and was successfully introduced into clinical practice.

Further, we have proposed the hypothesis of a passive role of the damaged extracellular matrix in the initiation of calcification of heart valve and blood vessel grafts. It has been shown that if graft had any damage of extracellular matrix was observed elastic lamella-associated calcification of implants. Currently, the mechanism of passive calcification of elastin (without recipient cells) is  the subject of our study.

The scientific significance of the results is to provide a scientific basis for targeted development of highperformance biomaterials for replacement and reconstructive cardiovascular surgery, for understanding the mechanisms of vascular calcification in organism, in particular, Mönckeberg calcinosis. Social significance of the work is determined by the relevance of this research to create high effective biomaterials and thus to improve the efficiency of surgical treatment in cardiovascular surgery.

This work is supported by Government of RF (No. 14.Z50.31.0028), Scholarship grant of the President of the RF (Grant №СП-6867.2013.4, №СП-1519.2015.4) and project of Ministry of Education and Science (№768).