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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">kpccz</journal-id><journal-title-group><journal-title xml:lang="ru">Комплексные проблемы сердечно-сосудистых заболеваний</journal-title><trans-title-group xml:lang="en"><trans-title>Complex Issues of Cardiovascular Diseases</trans-title></trans-title-group></journal-title-group><issn pub-type="ppub">2306-1278</issn><issn pub-type="epub">2587-9537</issn><publisher><publisher-name>Federal State Budgetary Institution “Research Institute for Complex Issues of Cardiovascular Diseases”</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="doi">10.17802/2306-1278-2025-14-3-27-39</article-id><article-id custom-type="elpub" pub-id-type="custom">kpccz-1471</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>ОРИГИНАЛЬНЫЕ ИССЛЕДОВАНИЯ. Патологическая физиология</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="en"><subject>ORIGINAL STUDIES. Pathological physiology</subject></subj-group></article-categories><title-group><article-title>МОРФОГЕНЕТИЧЕСКИЕ ОСОБЕННОСТИ РЕМОДЕЛИРОВАНИЯ БИОДЕГРАДИРУЕМЫХ СОСУДИСТЫХ ПРОТЕЗОВ В ЗАВИСИМОСТИ ОТ ИХ ФУНКЦИОНАЛЬНОЙ СОСТАВЛЯЮЩЕЙ</article-title><trans-title-group xml:lang="en"><trans-title>MORPHOGENETIC FEATURES OF REMODELING OF BIODEGRADABLE VASCULAR GRAFTS DEPENDING ON THEIR FUNCTIONAL COMPONENT</trans-title></trans-title-group></title-group><contrib-group><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-8826-9244</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Ханова</surname><given-names>Марьям Юрисовна</given-names></name><name name-style="western" xml:lang="en"><surname>Khanova</surname><given-names>Mariam Yu.</given-names></name></name-alternatives><bio xml:lang="ru"><p>младший научный сотрудник лаборатории клеточных технологий отдела экспериментальной медицины федерального государственного бюджетного научного учреждения «Научно-исследовательский институт комплексных проблем сердечно-сосудистых заболеваний», Кемерово, Российская Федерация</p></bio><bio xml:lang="en"><p>Junior Researcher at the Laboratory of Cellular Technologies of the Department of Experimental Medicine, Federal State Budgetary Institution “Research Institute for Complex Issues of Cardiovascular Diseases”, Kemerovo, Russian Federation</p></bio><email xlink:type="simple">khanovam@gmail.com</email><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-2500-2147</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Кривкина</surname><given-names>Евгения Олеговна</given-names></name><name name-style="western" xml:lang="en"><surname>Krivkina</surname><given-names>Evgenia O.</given-names></name></name-alternatives><bio xml:lang="ru"><p>младший научный сотрудник лаборатории клеточных технологий отдела экспериментальной медицины федерального государственного бюджетного научного учреждения «Научно-исследовательский институт комплексных проблем сердечно-сосудистых заболеваний», Кемерово, Российская Федерация</p></bio><bio xml:lang="en"><p>Junior Researcher at the Laboratory of Cellular Technologies of the Department of Experimental Medicine, Federal State Budgetary Institution “Research Institute for Complex Issues of Cardiovascular Diseases”, Kemerovo, Russian Federation</p></bio><email xlink:type="simple">leonora92@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/0000-0002-9430-937X</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Сенокосова</surname><given-names>Евгения Андреевна</given-names></name><name name-style="western" xml:lang="en"><surname>Senokosova</surname><given-names>Evgenia A.</given-names></name></name-alternatives><bio xml:lang="ru"><p>кандидат биологических наук заведующая лабораторией клеточных технологий отдела экспериментальной медицины федерального государственного бюджетного научного учреждения «Научно-исследовательский институт комплексных проблем сердечно-сосудистых заболеваний», Кемерово, Российская Федерация</p></bio><bio xml:lang="en"><p>PhD, Head of the Laboratory of Cellular Technologies of the Department of Experimental Medicine, Federal State Budgetary Institution “Research Institute for Complex Issues of Cardiovascular Diseases”, Kemerovo, Russian Federation</p></bio><email xlink:type="simple">sergeewa.ew@yandex.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/0000-0002-4467-8732</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Синицкая</surname><given-names>Анна Викторовна</given-names></name><name name-style="western" xml:lang="en"><surname>Sinitskaya</surname><given-names>Anna V.</given-names></name></name-alternatives><bio xml:lang="ru"><p>кандидат биологических наук научный сотрудник лаборатории геномной медицины отдела экспериментальной медицины федерального государственного бюджетного научного учреждения «Научно-исследовательский институт комплексных проблем сердечно-сосудистых заболеваний», Кемерово, Российская Федерация</p></bio><bio xml:lang="en"><p>PhD, Researcher at the Laboratory of Cellular Technologies of the Department of Experimental Medicine, Federal State Budgetary Institution “Research Institute for Complex Issues of Cardiovascular Diseases”, Kemerovo, Russian Federation</p></bio><email xlink:type="simple">cepoav1991@gmail.com</email><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-4146-3373</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Матвеева</surname><given-names>Вера Геннадьевна</given-names></name><name name-style="western" xml:lang="en"><surname>Matveeva</surname><given-names>Vera G.</given-names></name></name-alternatives><bio xml:lang="ru"><p>кандидат медицинских наук старший научный сотрудник лаборатории клеточных технологий отдела экспериментальной медицины федерального государственного бюджетного научного учреждения «Научно-исследовательский институт комплексных проблем сердечно-сосудистых заболеваний», Кемерово, Российская Федерация</p></bio><bio xml:lang="en"><p>PhD, Senior Researcher at the Laboratory of Cellular Technologies of the Department of Experimental Medicine, Federal State Budgetary Institution “Research Institute for Complex Issues of Cardiovascular Diseases”, Kemerovo, Russian Federation</p></bio><email xlink:type="simple">matveeva_vg@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/0000-0002-8846-5077</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Миронов</surname><given-names>Андрей Владимироваич</given-names></name><name name-style="western" xml:lang="en"><surname>Mironov</surname><given-names>Andrey V.</given-names></name></name-alternatives><bio xml:lang="ru"><p>кандидат медицинских наук младший научный сотрудник лаборатории клеточных технологий отдела экспериментальной медицины федерального государственного бюджетного научного учреждения «Научно-исследовательский институт комплексных проблем сердечно-сосудистых заболеваний», Кемерово, Российская Федерация</p></bio><bio xml:lang="en"><p>PhD, Junior Researcher at the Laboratory of Cellular Technologies of the Department of Experimental Medicine, Federal State Budgetary Institution “Research Institute for Complex Issues of Cardiovascular Diseases”, Kemerovo, Russian Federation</p></bio><email xlink:type="simple">a.mir.80@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/0000-0002-8874-0788</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Антонова</surname><given-names>Лариса Валерьевна</given-names></name><name name-style="western" xml:lang="en"><surname>Antonova</surname><given-names>Larisa V.</given-names></name></name-alternatives><bio xml:lang="ru"><p>доктор медицинских наук ведущий научный сотрудник лабораторией клеточных технологий отдела экспериментальной медицины федерального государственного бюджетного научного учреждения «Научно-исследовательский институт комплексных проблем сердечно-сосудистых заболеваний», Кемерово, Российская Федерация</p></bio><bio xml:lang="en"><p>PhD, Leading Researcher at the Laboratory of Cellular Technologies of the Department of Experimental Medicine, Federal State Budgetary Institution “Research Institute for Complex Issues of Cardiovascular Diseases”, Kemerovo, Russian Federation</p></bio><email xlink:type="simple">antonova.la@mail.ru</email><xref ref-type="aff" rid="aff-1"/></contrib></contrib-group><aff-alternatives id="aff-1"><aff xml:lang="ru">Федеральное государственное бюджетное научное учреждение «Научно-исследовательский институт комплексных проблем сердечно-сосудистых заболеваний»<country>Россия</country></aff><aff xml:lang="en">Federal State Budgetary Institution “Research Institute for Complex Issues of Cardiovascular Diseases”<country>Russian Federation</country></aff></aff-alternatives><pub-date pub-type="collection"><year>2025</year></pub-date><pub-date pub-type="epub"><day>01</day><month>07</month><year>2025</year></pub-date><volume>14</volume><issue>3</issue><fpage>27</fpage><lpage>39</lpage><permissions><copyright-statement>Copyright &amp;#x00A9; Ханова М.Ю., Кривкина Е.О., Сенокосова Е.А., Синицкая А.В., Матвеева В.Г., Миронов А.В., Антонова Л.В., 2025</copyright-statement><copyright-year>2025</copyright-year><copyright-holder xml:lang="ru">Ханова М.Ю., Кривкина Е.О., Сенокосова Е.А., Синицкая А.В., Матвеева В.Г., Миронов А.В., Антонова Л.В.</copyright-holder><copyright-holder xml:lang="en">Khanova M.Y., Krivkina E.O., Senokosova E.A., Sinitskaya A.V., Matveeva V.G., Mironov A.V., Antonova L.V.</copyright-holder><license 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.nii-kpssz.com/jour/article/view/1471">https://www.nii-kpssz.com/jour/article/view/1471</self-uri><abstract><sec><title>Основные положения</title><p>Основные положения</p><p>При разработке сосудистых протезов часто встречаемыми осложнениями являются гиперплазия неоинтимы и аневризмообразование. Для эффективной сборки новообразованной ткани на основе биодеградируемых протезов и направленного ремоделирования актуальным представляется создание дополнительных стимулов. Проведена сравнительная оценка ремоделирования на основе биодеградируемых сосудистых протезов в зависимости от наличия проангиогенных факторов и влияния антибактериального агента на модели сонной артерии овцы.</p></sec><sec><title> </title><p> </p></sec><sec><title>Резюме</title><p>Резюме</p></sec><sec><title>Цель</title><p>Цель. Сравнительное описание ремоделирования двух типов протезов в зависимости от наличия или отсутствия проангиогенных факторов и влияния антибактериального агента.</p></sec><sec><title>Материалы и методы</title><p>Материалы и методы. Изготовлены два типа биодеградируемых сосудистых протезов из поли(3-гидроксибутирата-ко-3-гидроксивалерата) (PHBV) и поли(ε-капролактона) (PCL) методом электроспиннинга. На внутренней поверхности первого типа сосудистых протезов PHBV/PCL/Ilo/А формировали лекарственное покрытие из катионного амфифила и илопроста, а также создавали армирующую спираль методом послойного наплавления. При изготовлении второго типа сосудистых протезов PHBV/PCL/GFmix/Hep/Ilo на этапе электроспиннинга вводили композицию ростовых факторов (GFmix): фактор роста эндотелия сосудов (VEGF), основной фактор роста фибробластов (bFGF) и хемоаттрактантную молекулу (SDF-1α). Дополнительно для придания тромборезистентных свойств модифицировали илопрост и гепарин посредством комплексообразования через поливинилпирролидон. Полученные протезы имплантировали в сонную артерию овцы (n = 12). Эксплантированные сосудистые протезы исследованы с помощью гистологического и иммунофлуоресцентного окрашивания, а также исследован генетический профиль ремоделирования сосудистой стенки методом количественной полимеразной цепной реакции.</p></sec><sec><title>Результаты</title><p>Результаты. По результатам гистологического и иммунофлуоресцентного исследований на основе протезов PHBV/PCL/GFmix/Hep/Ilo сформирована трехслойная сосудистая неоткань без отложений кальцификатов. Генетическое исследование показало, что через 6 мес. после имплантации ремоделирование в сравнении с сонной артерией овцы протекало в воспалительной среде (IL1A, IL4, IL8), а также характеризовалось воспалительной активацией эндотелия (KLF4). Сосудистая стенка, сформированная на основе протезов PHBV/PCL/Ilo/А, отличалась наличием гиперплазии неоинтимы, повышенной экспрессией противовоспалительного IL10, что может указывать на развитие хронического воспалительного процесса. Также характеризовалась формированием сети vasa vasorum в адвентиции и повышенной экспрессией гена CXCR4, кодирующего рецептор, связанный с ангиогенезом. В двух исследуемых группах не обнаружено признаков острого воспаления, однако выявлено расширение сосудистого просвета по типу аневризматического расширения. При сравнении неоткани, сформированной на основе протезов PHBV/PCL/GFmix/Hep/Ilo, с неотканью на основе протезов PHBV/PCL/Ilo/А наблюдался меньший уровень экспрессии провоспалительных и противовоспалительных цитокинов, а также молекул воспалительной и протромботической активации эндотелиальных клеток.</p></sec><sec><title>Заключение</title><p>Заключение. Ростовые факторы, введенные в состав протезов PHBV/PCL/GFmix/Hep/Ilo, способны модулировать микроокружение, которое через полгода после имплантации привело к формированию трехслойной сосудистой неоткани. Данная неоткань, в сравнении с таковой на основе PHBV/PCL/Ilo/А, характеризуется снижением уровня экспрессии про- и противовоспалительных цитокинов и хемокина, а также молекул воспалительной и протромботической активации эндотелия.</p></sec></abstract><trans-abstract xml:lang="en"><sec><title>Highlight</title><p>Highlight</p><p>Neointimal hyperplasia and aneurysm formation are common complications in the development of vascular grafts. For the effective assembly of newly formed tissue based on biodegradable grafts and targeted remodeling, the creation of additional incentives is an urgent issue. The study involved comparative assessment of remodeling based on biodegradable vascular grafts, depending on the presence of proangiogenic factors and the effect of an antibacterial agent on the sheep carotid artery model.</p></sec><sec><title> </title><p> </p></sec><sec><title>Abstract</title><p>Abstract</p></sec><sec><title>Aim</title><p>Aim. To comparatively describe remodeling of two types of grafts, depending on the presence or absence of proangiogenic factors and the influence of an antibacterial agent.</p></sec><sec><title>Methods</title><p>Methods. Two types of biodegradable vascular grafts were made from poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) and poly(ε-caprolactone) (PCL) by electrospinning. On the inner surface of the PHBV/PCL/Ilo/A vascular grafts, a drug coating was formed from cationic amphiphile and iloprost, and a reinforcing spiral frame was created by extrusion. In the manufacture of the PHBV/PCL/GFmix/Hep/Ilo vascular grafts, a composition of growth factors (GFmix) was introduced at the electrospinning stage: vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF) and a chemoattractant molecule (SDF-1α). Additionally, iloprost and heparin were modified by complexation via polyvinylpyrrolidone to impart thromboresistant properties. The resulting grafts were implanted into the carotid artery of a sheep (n = 12). The explanted vascular grafts were examined using histological and immunofluorescence staining, the genetic profile of vascular wall remodeling was studied by quantitative polymerase chain reaction.</p></sec><sec><title>Results</title><p>Results. According to the results of histological and immunofluorescence studies, a newly formed three-layer structure of vascular tissue without calcification deposits formed on the PHBV/PCL/GFmix/Hep/Ilo grafts. Genetic study showed that at 6 months of implantation, remodeling, compared to the sheep carotid artery, occurred in an inflammatory environment (IL1A, IL4, IL8), and was also characterized by inflammatory activation of the endothelium (KLF4). The newly formed vascular wall formed on the basis of the PHBV/PCL/Ilo/A grafts showed signs of neointimal hyperplasia and increased expression of anti-inflammatory IL10, which might reflect the development of a chronic inflammatory process. Moreover, it showed the formation of a vasa vasorum network in the adventitia and increased expression of the CXCR4 gene, encoding a receptor associated with angiogenesis. There were no signs of acute inflammation in both study groups, however, we detected aneurysmal expansion of vascular lumen. When comparing a newly formed vascular tissue formed on the PHBV/PCL/GFmix/Hep/Ilo grafts to a newly formed vascular tissue on the PHBV/PCL/Ilo/A grafts, we observed a lower level of expression of proinflammatory and anti-inflammatory cytokines, as well as molecules of inflammatory and prothrombotic activation of endothelial cells.</p></sec><sec><title>Conclusion</title><p>Conclusion. Growth factors introduced into the composition of the PHBV/PCL/GFmix/Hep/Ilo grafts are capable of modulating the microenvironment. After 6 months of implantation it led to the newly formed three-layer structure of vascular tissue, characterized by a decrease in the level of expression of pro- and anti-inflammatory cytokines and chemokines, as well as molecules of inflammatory and prothrombotic activation of the endothelium compared to the newly formed vascular tissue on the PHBV/PCL/Ilo/A grafts.</p></sec></trans-abstract><kwd-group xml:lang="ru"><kwd>Сосудистые протезы</kwd><kwd>Ремоделирование</kwd><kwd>Биодеградируемые полимеры</kwd><kwd>Сосудистый протез малого диаметра</kwd><kwd>Атромбогенное лекарственное покрытие</kwd><kwd>Катионный амфифил</kwd></kwd-group><kwd-group xml:lang="en"><kwd>Vascular grafts</kwd><kwd>Remodeling</kwd><kwd>Biodegradable polymers</kwd><kwd>Small-diameter vascular graft</kwd><kwd>Atrombogenic drug coating</kwd><kwd>Cationic amphiphile</kwd></kwd-group><funding-group xml:lang="ru"><funding-statement>Исследование выполнено в рамках фундаментальной темы НИИ КПССЗ № 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-group></article-meta></front><back><ref-list><title>References</title><ref id="cit1"><label>1</label><citation-alternatives><mixed-citation xml:lang="ru">Di Francesco D., Pigliafreddo A., Casarella S., Di Nunno L., Mantovani D., Boccafoschi F. 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