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<article article-type="research-article" dtd-version="1.3" xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xml:lang="ru"><front><journal-meta><journal-id journal-id-type="publisher-id">transplantologiya</journal-id><journal-title-group><journal-title xml:lang="ru">Трансплантология</journal-title><trans-title-group xml:lang="en"><trans-title>Transplantologiya. The Russian Journal of Transplantation</trans-title></trans-title-group></journal-title-group><issn pub-type="ppub">2074-0506</issn><issn pub-type="epub">2542-0909</issn><publisher><publisher-name>IPO Association of Transplantologists</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="doi">10.23873/2074-0506-2023-15-4-515-528</article-id><article-id custom-type="elpub" pub-id-type="custom">transplantologiya-829</article-id><article-categories><subj-group subj-group-type="heading"><subject>Research Article</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="ru"><subject>ОБЗОРНЫЕ СТАТЬИ И ЛЕКЦИИ</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="en"><subject>REVIEW ARTICLES AND LECTURES</subject></subj-group></article-categories><title-group><article-title>Современный взгляд на кальцификацию ксенобиопротезов клапанов сердца и стратегии их антикальцификационной защиты</article-title><trans-title-group xml:lang="en"><trans-title>Modern view on calcification of xenogenic bioprosthetic heart valves and their anti-calcification treatment strategies</trans-title></trans-title-group></title-group><contrib-group><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0001-6099-0315</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Костюнин</surname><given-names>А. Е.</given-names></name><name name-style="western" xml:lang="en"><surname>Kostyunin</surname><given-names>A. E.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Александр Евгеньевич Костюнин - канд. биол. наук, научный сотрудник лаборатории новых биоматериалов.</p><p>650002, Кемерово, Сосновый б-р, д. 6</p></bio><bio xml:lang="en"><p>Alexander E. Kostyuni - Cand. Sci. (Biol.), Researcher of the Laboratory of New Biomaterials.</p><p>6 Sosnovy Blvd., Kemerovo 650002</p></bio><email xlink:type="simple">rhabdophis_tigrina@mail.ru</email><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0003-4890-0393</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Глушкова</surname><given-names>Т. В.</given-names></name><name name-style="western" xml:lang="en"><surname>Glushkova</surname><given-names>T. V.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Татьяна Владимировна Глушкова - канд. биол. наук, старший научный сотрудник лаборатории новых биоматериалов.</p><p>650002, Кемерово, Сосновый б-р, д. 6</p></bio><bio xml:lang="en"><p>Tatyana V. Glushkova - Cand. Sci. (Biol.), Senior Researcher of the Laboratory of New Biomaterials.</p><p>6 Sosnovy Blvd., Kemerovo 650002</p></bio><email xlink:type="simple">bio.tvg@mail.ru</email><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0003-1341-204X</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Стасев</surname><given-names>А. Н.</given-names></name><name name-style="western" xml:lang="en"><surname>Stasev</surname><given-names>A. N.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Александр Николаевич Стасев - канд. мед. наук, научный сотрудник лаборатории пороков сердца.</p><p>650002, Кемерово, Сосновый б-р, д. 6</p></bio><bio xml:lang="en"><p>Alexander N. Stasev - Cand. Sci. (Med.) Researcher of the Laboratory of Heart Diseases.</p><p>6 Sosnovy Blvd., Kemerovo 650002</p></bio><email xlink:type="simple">StasAN@kemcardio.ru</email><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0001-7477-3979</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Овчаренко</surname><given-names>Е. А.</given-names></name><name name-style="western" xml:lang="en"><surname>Ovcharenko</surname><given-names>E. A.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Евгений Андреевич Овчаренко - кандидат технических наук, заведующий лабораторией новых биоматериалов.</p><p>650002, Кемерово, Сосновый б-р, д. 6</p></bio><bio xml:lang="en"><p>Evgeny A. Ovcharenko - Cand. Sci. (Tech.), Head of the Laboratory of New Biomaterials.</p><p>6 Sosnovy Blvd., Kemerovo 650002</p></bio><email xlink:type="simple">ov.eugene@gmail.com</email><xref ref-type="aff" rid="aff-1"/></contrib></contrib-group><aff-alternatives id="aff-1"><aff xml:lang="ru"><institution>ФГБНУ «НИИ комплексных проблем сердечно-сосудистых заболеваний»</institution><country>Россия</country></aff><aff xml:lang="en"><institution>Research Institute for Complex Issues of Cardiovascular Diseases</institution><country>Russian Federation</country></aff></aff-alternatives><pub-date pub-type="collection"><year>2023</year></pub-date><pub-date pub-type="epub"><day>20</day><month>12</month><year>2023</year></pub-date><volume>15</volume><issue>4</issue><fpage>515</fpage><lpage>528</lpage><permissions><copyright-statement>Copyright &amp;#x00A9; Костюнин А.Е., Глушкова Т.В., Стасев А.Н., Овчаренко Е.А., 2023</copyright-statement><copyright-year>2023</copyright-year><copyright-holder xml:lang="ru">Костюнин А.Е., Глушкова Т.В., Стасев А.Н., Овчаренко Е.А.</copyright-holder><copyright-holder xml:lang="en">Kostyunin A.E., Glushkova T.V., Stasev A.N., Ovcharenko E.A.</copyright-holder><license xml:lang="ru" license-type="creative-commons-attribution" xlink:href="https://creativecommons.org/licenses/by/4.0/" xlink:type="simple"><license-p>Данная работа распространяется под лицензией Creative Commons Attribution 4.0.</license-p></license><license xml:lang="en" license-type="creative-commons-attribution" xlink:href="https://creativecommons.org/licenses/by/4.0/" xlink:type="simple"><license-p>This work is licensed under a Creative Commons Attribution 4.0 License.</license-p></license></permissions><self-uri xlink:href="https://www.jtransplantologiya.ru/jour/article/view/829">https://www.jtransplantologiya.ru/jour/article/view/829</self-uri><abstract><sec><title>Цель</title><p>Цель. Цель настоящего обзора состоит в анализе публикаций, посвященных исследованиям патофизиологических механизмов кальцификации ксеногенных биопротезов клапанов сердца, а также в обосновании новых перспективных методов антикальцификационной защиты этих медицинских изделий.</p></sec><sec><title>Материал и методы</title><p>Материал и методы. Анализируемые статьи представлены в базах данных и электронных библиотеках PubMed, Google Scholar и eLibrary. Поисковые запросы основаны на сочетаниях слов "bioprosthetic heart valves", "structural valve degeneration", "calcification", "cyclic loading", "inflammation", "proteolysis", "proteolytic enzymes", "decellularization", "anticalcium treatment". Также поиск происходил с использованием списков литературы, приведенных в релевантных статьях. Предпочтение отдавали работам, опубликованным с января 2013 по январь 2023 года.</p></sec><sec><title>Результаты</title><p>Результаты. Нами рассмотрены ключевые аспекты кальцификации ксенобиопротезов клапанов сердца и основные стратегии их антикальцификационной обработки. Показано, что за кальцификацией искусственных клапанов стоит сложный комплекс механизмов, который включает, но не ограничивается: 1) связыванием кальция в химически стабилизированном биоматериале свободными группами консерванта; 2) осаждением кальция на остаточных клетках донора и клеточном дебрисе; 3) возникновением прокальцифицирующих изменений в биоткани под действием протеолиза, механического и оксидативного стресса; 4) клеточно-опосредованной биоминерализацией. Несмотря на современные многоступенчатые подходы к консервации биологической ткани, включающие обработку химическими агентами, которые препятствуют осаждению кальция в ее структуре, решить проблему кальцификации ксенобиопротезов пока не удалось. Вероятно, причина неудачи заключается в гетерогенности патофизиологических механизмов кальцификации: разработанные на текущий момент методы антикальцификационной защиты не способны противостоять всем путям развития кальциноза искусственных клапанов.</p></sec><sec><title>Заключение</title><p>Заключение. Кальцификация створчатого аппарата ксенобиопротезов клапанов сердца – это сложный многофакторный процесс и главная причина дисфункций рассматриваемых медицинских изделий. Потенциально инновационный подход с использованием гидрогелей полимеров в качестве наполнителя биоткани может полностью предотвратить ее кальцификацию.</p></sec></abstract><trans-abstract xml:lang="en"><sec><title>Aim</title><p>Aim. The aim of this review was to analyze publications describing studies focusing on the pathophysiological mechanisms of calcification of bioprosthetic heart valves, and to substantiate new and promising methods of calcification prevention for the implantable medical devices.</p></sec><sec><title>Material and methods</title><p>Material and methods. Databases and electronic libraries such as PubMed, Google Scholar and eLibrary were used for searching relevant articles. Search queries included the following word combinations: “bioprosthetic heart valves”, “structural valve degeneration”, “calcification”, “cyclic loading”, “inflammation”, “proteolysis”, “proteolytic enzymes”, “decellularization”, “anticalcification treatment”. The references in relevant articles were used for the search as well. Preference was given to works published from January 2013 to January 2023.</p></sec><sec><title>Results</title><p>Results. We have considered the key aspects of bioprosthetic heart valves calcification and the main strategies of calcification prevention. Calcification of bioprosthetic heart valves incorporates a complex set of mechanisms that includes, but is not limited to: 1) binding of calcium in chemically stabilized biomaterial by free groups of the preservative; 2) precipitation of calcium on residual donor cells and cell debris; 3) pro-calcifying changes in biological material due to proteolysis, mechanical and oxidative stress; 4) cell-mediated biomineralization. Despite modern advances in biopreservation, such as treatment with chemical agents that prevent the deposition of calcium, the problem of bioprosthetic heart valves calcification still prevails. The cause of it lies in the heterogeneity of the pathophysiological mechanisms behind the mineralization of biomaterial: the currently developed methods of calcification prevention cannot block all ways of bioprosthetic heart valves calcification.</p></sec><sec><title>Conclusion</title><p>Conclusion. Calcification of bioprosthetic heart valves leaflets is a complex process that underlies the main cause of dysfunction of the medical devices. Supposedly, a new innovative approach that involves polymer hydrogel filler in biomaterials can completely prevent its calcification.</p></sec></trans-abstract><kwd-group xml:lang="ru"><kwd>биопротезы клапанов сердца</kwd><kwd>структурная дегенерация клапана</kwd><kwd>кальцификация</kwd><kwd>гидроксиапатит</kwd><kwd>остеогенные кальций-связывающие протеины</kwd><kwd>циклические нагрузки</kwd><kwd>иммунное отторжение</kwd></kwd-group><kwd-group xml:lang="en"><kwd>bioprosthetic heart valves</kwd><kwd>structural valve degeneration</kwd><kwd>calcification</kwd><kwd>hydroxyapatite</kwd><kwd>calcium-binding proteins</kwd><kwd>cyclic loading</kwd><kwd>immune rejection</kwd></kwd-group><funding-group><funding-statement xml:lang="ru">Работа выполнена при поддержке комплексной программы фундаментальных научных исследований СО РАН в рамках фундаментальной темы ФГБНУ «НИИ комплексных проблем сердечно-сосудистых заболеваний» № 0419-2022-0001 «Молекулярные, клеточные и биомеханические механизмы патогенеза сердечно-сосудистых заболеваний в разработке новых методов лечения заболеваний сердечно-сосудистой системы на основе персонифицированной фармакотерапии, внедрения малоинвазивных медицинских изделий, биоматериалов и тканеинженерных имплантатов»</funding-statement><funding-statement xml:lang="en">This research was funded by the Complex Program of Basic Research under the Siberian Branch of the Russian Academy of Sciences within the Basic Research Topic No. 04192022-0001 of the Research Institute for Complex Issues of Cardiovascular Diseases entitled "Molecular, cellular and biomechanical mechanisms of the pathogenesis of cardiovascular diseases in the development of new cardiovascular disease treatments based on personalized pharmacotherapy, the introduction of minimally invasive medical devices, biomaterials and</funding-statement></funding-group></article-meta></front><back><ref-list><title>References</title><ref id="cit1"><label>1</label><citation-alternatives><mixed-citation xml:lang="ru">Otto CM, Nishimura RA, Bonow RO, Carabello BA, Erwin JP, Gentile F, et al. 2020 ACC/AHA guideline for the management of patients with valvular heart disease: a report of the American College of Cardiology/American Heart Association Joint Committee on clinical practice guidelines. 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