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 Federation10.15825/1995-1191-2024-2-105-118vtio-1731Research ArticleРегенеративная медицина и клеточные технологииRegenerative Medicine and Cell TechnologiesГистологические и генетические особенности ремоделирования тканеинженерных сосудистых протезов малого диаметра: результаты шестимесячной имплантации на модели овцыHistologic and genetic features of remodeling of tissue-engineered small-diameter vascular grafts: outcomes of six-month implantation in a sheep modelСенокосоваЕ. А.SenokosovaE. A.

Кемерово

Kemerovo

sergeewa.ew@yandex.ruКривкинаЕ. О.KrivkinaE. O.

Кривкина Евгения Олеговна

650002, Кемерово, Сосновый б-р, д. 6

Тел. (908) 946-66-39

Evgeniya Krivkina

6, Sosnovy Bul’var, Kemerovo, 650002

Phone: (908) 946-66-39

leonora92@mail.ruВеликановаЕ. А.VelikanovaE. A.

Кемерово

Kemerovo

velikanova_ea@mail.ruСиницкаяА. В.SinitskayaA. V.

Кемерово

Kemerovo

annacepokina@mail.ruМироновА. В.MironovA. V.

Кемерово

Kemerovo

a.mir.80@mail.ruШабаевА. Р.ShabaevA. R.

Кемерово

Kemerovo

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

Кемерово

Kemerovo

khanovam@gmail.comТоргунаковаЕ. А.TorgunakovaE. A.

Кемерово

Kemerovo

leonora92@mail.ruАнтоноваЛ. В.AntonovaL. V.

Кемерово

Kemerovo

antonova.la@mail.ruФГБНУ «Научно-исследовательский институт комплексных проблем сердечно-сосудистых заболеваний»РоссияResearch Institute for Complex Issues of Cardiovascular DiseasesRussian Federation202431012024262105118Copyright © Сенокосова Е.А., Кривкина Е.О., Великанова Е.А., Синицкая А.В., Миронов А.В., Шабаев А.Р., Ханова М.Ю., Торгунакова Е.А., Антонова Л.В., 20242024Сенокосова Е.А., Кривкина Е.О., Великанова Е.А., Синицкая А.В., Миронов А.В., Шабаев А.Р., Ханова М.Ю., Торгунакова Е.А., Антонова Л.В.Senokosova E.A., Krivkina E.O., Velikanova E.A., Sinitskaya A.V., Mironov A.V., Shabaev A.R., Khanova M.Y., Torgunakova E.A., Antonova L.V.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/1731

Модифицирование поверхности полимерных каркасов лекарственными препаратами во избежание тромбообразования и инфицирования – перспективное направление тканевой инженерии, позволяющее также ускорить их ремоделирование и улучшить долгосрочную проходимость.

Цель

Цель: изучить гистологические и генетические особенности ремоделирования тканеинженерных сосудистых протезов малого диаметра с атромбогенным лекарственным покрытием и усиленным внешним каркасом, имплантированных в сонную артерию овцы.

Материалы и методы

Материалы и методы. Методом электроспиннинга изготовлены матриксы ∅4 мм из поли(ε-капролактонона) (PCL) с последующим созданием на их внешней поверхности армирующего спиралевидного каркаса из PCL посредством экструзии. Для предупреждения тромбообразования и инфицирования изготовленные протезы модифицировали илопростом и катионным амфифилом посредством комплексообразования через поливинилпирролидон (PVP). Проведены работы по оценке с помощью ИК-спектроскопии формирования покрытия на основе PVP, изучению физико-механических свойств протезов в продольном и поперечном направлениях, имплантации сосудистых протезов в сонную артерию овцы. Для оценки и контроля проходимости имплантированных протезов проводили ультразвуковое исследование (УЗИ) с функцией Доплера на 1-е, 5-е сутки, затем через 1, 3 и 6 месяцев. Эксплантированные образцы изучены методами гистологического и иммунофлуоресцентного анализов, проведена оценка профиля генной экспрессии.

Результаты

Результаты. Согласно данным УЗИ-мониторинга, на 1-е и 5-е сутки после имплантации проходимость сосудистых протезов составила 100%. Через 1 месяц проходимость снизилась до 83,3%, к концу срока имплантации (6 месяцев) проходимость составила 50%, без развития аневризмообразования и отслойки армирующего каркаса. Результаты гистологического и иммунофлуоресцентного исследований проходимых протезов показали формирование на их основе новообразованной трехслойной структуры сосудистой ткани, без признаков воспаления и кальцификации. Однако, несмотря на структурное сходство новообразованной сосудистой ткани с нативной тканью сонной артерии овцы, анализ профиля генной экспрессии выявил различия по генетическому профилю: обнаружено снижение уровня экспрессии генов CNN и SNA12 в неоткани и увеличение уровня CTSB, TNFa, TGFb.

Заключение

Заключение. Модифицированные полимерные сосудистые каркасы показали хорошее ремоделирование стенки протеза, без аневризмообразования. Выявленные генетические отличия новообразованной ткани от нативной логичны ввиду формирования ее на базе искусственного полимерного каркаса. Дальнейшие исследования усиленных полимерных каркасов будут направлены на усовершенствование внутренней поверхности с целью повышения их тромборезистентности.

Surface modification of polymeric scaffolds with drugs to avoid thrombus formation and infection is a promising area in tissue engineering, which also makes it possible to accelerate the remodeling of such scaffolds and improve long-term patency.

The objective of this paper is to study the histologic and genetic features of remodeling of tissue-engineered small-diameter vascular grafts (SDVGs) with antithrombogenic drug-coated and reinforced external scaffolds, implanted into a sheep carotid artery.

Materials and methods

Materials and methods. Poly(ε-caprolactone) (PCL) matrices, ∅4 mm in diameter, were fabricated via electrospinning, followed by creation of a reinforcing spiral PCL scaffold on their outer surface by extrusion. To prevent thrombus formation and infection, the fabricated grafts were modified with iloprost and cationic amphiphile by complexation through polyvinylpyrrolidone (PVP). The work was carried out to evaluate, by infrared spectroscopy, the formation of PVP-based coating, to study the physical and mechanical properties of the grafts in longitudinal and transverse directions, and to implant the vascular grafts (VGs) into a sheep carotid artery. To assess and control the patency of the implanted grafts, Doppler ultrasound was performed at days 1 and 5, then at 1, 3 and 6 months. The explanted samples were studied via histological and immunofluorescent analyses; gene expression profile was evaluated.

Results

Results. Ultrasound on days 1 and 5 after implantation showed the patency of vascular grafts to be 100%. At 1 month, the patency decreased to 83.3%; patency was 50% by the end of the implantation period (6 months), without aneurysm formation and detachment of the reinforcing scaffold. Histological and immunofluorescence studies of patent grafts showed the formation of a newly formed three-layer vascular tissue structure on their basis, without signs of inflammation and calcification. However, despite the structural similarity between the newly formed vascular tissue and the native tissue of a sheep carotid artery, analysis of the gene expression profile revealed some differences in terms of genetic profile: CNN and SNA12 expression levels in the neotissue decreased, and those of CTSB, TNFa, and TGFb increased.

Conclusion

Conclusion. Modified polymeric vascular scaffolds showed good remodeling of the prosthetic wall, without aneurysm formation. The identified genetic differences between newly formed tissue and native tissue are logical in view of formation on the basis of the artificial polymeric scaffold. Further research on reinforced polymeric scaffolds will be aimed at improving the inner surface in order to improve their thromboresistance.

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