vtioВестник трансплантологии и искусственных органовRussian Journal of Transplantology and Artificial Organs1995-1191Academician V.I.Shumakov National Medical Research Center of Transplantology and Artificial Organs", Ministry of Health of the Russian Federation10.15825/1995-1191-2022-3-80-93vtio-1493Research ArticleРегенеративная медицина и клеточные технологииRegenerative Medicine and Cell TechnologiesРезультаты преклинических испытаний биодеградируемых сосудистых протезов малого диаметра на модели овцыResults of preclinical trials in a sheep model of biodegradable small-diameter vascular graftsАнтоноваЛ. В.AntonovaL. V.

Кемерово

Kemerovo

КривкинаЕ. О.KrivkinaE. O.

Кривкина Евгения Олеговна

Адрес: 650002, Кемерово, Сосновый бульвар, д. 6Тел. (908) 946-66-39

Evgeniya Krivkina

Address: 6, Sosnovy Boulevard, Kemerovo, 650002Phone: (908) 946-66-39

leonora92@mail.ruХановаМ. Ю.KhanovaM. Yu.

Кемерово

Kemerovo

ВеликановаЕ. А.VelikanovaE. A.

Кемерово

Kemerovo

МатвееваВ. Г.MatveevaV. G.

Кемерово

Kemerovo

МироновА. В.MironovА. V.

Кемерово

Kemerovo

ШабаевА. Р.ShabaevA. R.

Кемерово

Kemerovo

СенокосоваЕ. А.SenokosovaЕ. A.

Кемерово

Kemerovo

ГлушковаТ. В.GlushkovaT. V.

Кемерово

Kemerovo

СиницкийМ. Ю.SinitskyM. Yu.

Кемерово

Kemerovo

МухамадияровР. А.MukhamadiyarovR. А.

Кемерово

Kemerovo

БарбарашЛ. С.BarbarashL. S.

Кемерово

Kemerovo

ФГБНУ «Научно-исследовательский институт комплексных проблем сердечно-сосудистых заболеваний»РоссияResearch Institute for Complex Issues of Cardiovascular DiseasesRussian Federation2022240820222438093Copyright © Антонова Л.В., Кривкина Е.О., Ханова М.Ю., Великанова Е.А., Матвеева В.Г., Миронов А.В., Шабаев А.Р., Сенокосова Е.А., Глушкова Т.В., Синицкий М.Ю., Мухамадияров Р.А., Барбараш Л.С., 20222022Антонова Л.В., Кривкина Е.О., Ханова М.Ю., Великанова Е.А., Матвеева В.Г., Миронов А.В., Шабаев А.Р., Сенокосова Е.А., Глушкова Т.В., Синицкий М.Ю., Мухамадияров Р.А., Барбараш Л.С.Antonova L.V., Krivkina E.O., Khanova M.Y., Velikanova E.A., Matveeva V.G., Mironov А.V., Shabaev A.R., Senokosova Е.A., Glushkova T.V., Sinitsky M.Y., Mukhamadiyarov R.А., Barbarash L.S.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://journal.transpl.ru/vtio/article/view/1493

Поверхностное модифицирование полимерных сосудистых матриксов – перспективная разработка для предотвращения тромбирования сосудистых протезов, улучшения долгосрочной проходимости и ускорения ремоделирования. Цель – изучить результаты долгосрочной проходимости протезов PHBV/PCL/GFmix с илопростом и гепарином, имплантированных в сонную артерию овец. Материалы и методы. Методом электроспиннинга изготовлены матриксы ∅4 мм из композиции полимеров поли(3-гидроксибутирата-ко-3-гидроксивалерата) (PHBV) и поли(ε-капролактонона) (PCL) с инкорпорированием в их состав эндотелиального фактора роста (VEGF), основного фактора роста фибробластов (bFGF) и хемоаттрактантной молекулы (SDF-1α). Затем изготовленные матриксы модифицировали илопростом и гепарином посредством комплексообразования через поливинилпирролидон (PVP). В качестве группы сравнения – синтетические протезы Gore-Tex. Оценены физико-механические свойства исследуемых групп матриксов, проведена оценка структуры поверхности сосудистых протезов до и после имплантации. Проведены работы по имплантации сосудистых протезов в сонную артерию овцы. Эксплантированные образцы изучены методами гистологического и иммунофлуоресцентного анализов, также проведен элементный состав полученных образцов сосудистых протезов и оценка профиля генной экспрессии. Результаты. Через сутки после имплантации проходимость сосудистых протезов PHBV/PCL/GFmixHep/Ilo составила 62,5%, тогда как у синтетических протезов Gore-Tex тромбоз был в 100% случаев. При этом через 18 месяцев имплантации проходимость биодеградируемых сосудистых протезов PHBV/PCL/GFmixHep/Ilo снизилась до 50%. Проходимые полимерные графты с лекарственным покрытием полностью резорбировались через 18 месяцев имплантации, а на их месте сформировалась аневризматически расширенная новообразованная сосудистая ткань. Заключение. Модифицирование поверхности полимерных протезов PHBV/PCL/GFmix лекарственным покрытием из илопроста и гепарина позволило улучшить результаты долгосрочной проходимости в сравнении с синтетическими протезами Gore-Tex.

Surface modification of polymer vascular matrices is a promising development for preventing vascular graft thrombosis, improving long-term patency and accelerating remodeling. Objective: to study the outcomes of long-term patency of PHBV/PCL/GFmix grafts with iloprost (Ilo) and heparin (Hep) implanted into the carotid artery of sheep. Materials and methods. Matrices ∅4 mm were fabricated by electrospinning from a polymer composition of poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) and poly(ε-caprolactone) (PCL) with incorporation of endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF) and chemoattractant molecule (SDF-1α). The fabricated matrices were then modified with Ilo and Hep by complexation via polyvinylpyrrolidone (PVP). Synthetic Gore-Tex grafts were used as a comparison group. The physical and mechanical properties of the studied matrix groups were evaluated, the surface structure of vascular grafts before and after implantation was assessed. Vascular grafts were implanted into the carotid artery of a sheep. The explanted samples were studied via histological and immunofluorescence analysis, the elemental composition of the obtained vascular graft samples was also assessed, and the gene expression profile was evaluated. Results. One day after implantation, the patency of PHBV/PCL/GFmixHep/Ilo vascular grafts was 62.5%, whereas synthetic Gore-Tex grafts had thrombosis in 100% of cases. At the same time, after 18 months of implantation, the patency of biodegradable PHBV/PCL/GFmixHep/Ilo vascular grafts decreased to 50%. Permeable drug-coated polymer grafts were completely reabsorbed after 18 months of implantation, and aneurysmally dilated newly-formed vascular tissue was formed in their place. Conclusion. Modification of the surface of PHBV/PCL/GFmix polymer grafts with Hep + Ilo coating improved long-term patency outcomes compared to synthetic Gore-Tex grafts.

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The authors declare that there are no conflicts of interest present.