Milestones in the Development of Bioprosthetic Mate-rials Based on the Mammalian Pericardium Tissue

The extensive research on the functional and structural prop-erties of mammalian pericardium transplants has become a basis for their wide use in different fields of reconstructive surgery. The transplants manifested themselves in the fabri-cation of prostheses (cardiac valves, blood vessels, etc.) and for their direct application as membranes in dentistry, closure of various cavities and other purposes. To eliminate the im-munogenicity and increase proteolytic stability, a number of techniques have been developed based on decellularization and crosslinking. As a crosslinker, GA is used most frequent-ly. However, less toxic functional analogues (genipin, epoxy-compound, isocyanates, carbodiimides, etc.) may potentially replace GA in the fabrication of pericardium tissue-based bio-plastic materials. In our study, we performed a comprehensive characterization of decellularized bovine pericardium cross-linked via different chemical mechanisms. Their structure, bi-odegradability, biomechanics and cytotoxicity were compared to that of non- crosslinked matrices pointing out individual advantages and drawbacks. In vivo study was performed with a clinically approved crosslinker, epoxy-compound, based on multiparametric bioimaging. We revealed the progression of hypoxia and severe calcification of the crosslinked implant in subcutaneous murine model. To overcome the biomechanics-associated side effects, we employed the processing of the samples in supercritical carbon dioxide medium. This allowed to reduce the stiffness without compromising cytotoxicity and biodegradability.The research was supported by the Russian Science Foundation under Grant No. 18-15-00401 (in vitro and in vivo studies) and Russian Foundation for Basic Research under Grant No. 18-33-00982 mol_a (supercritical carbon dioxide treatment).