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基于聚己内酯和聚氨酯并带有生长因子及抗血栓药物涂层的复合组织工程小口径血管移植物:表面超微结构、物理及力学性能

Composite Tissue-Engineered Small-Diameter Vascular Grafts Based on Polycaprolactone and Polyurethane with Growth Factors and Atrombogenic Drug Coatings: Surface Ultrastructure, Physical and Mechanical Properties.

作者信息

Senokosova E A, Prokudina E S, Krivkina E S, Glushkova T V, Velikanova E A, Khanova M Yu, Torgunakova E A, Matveeva V G, Antonova L V

机构信息

PhD, Researcher, Laboratory of Cell Technologies; Research Institute for Complex Issues of Cardiovascular Diseases, 6 Academician L.S. Barbarash Blvd, Kemerovo, 650002, Russia.

MD, PhD, Researcher, Laboratory of Tissue Engineering and Intravascular Imaging; Research Institute for Complex Issues of Cardiovascular Diseases, 6 Academician L.S. Barbarash Blvd, Kemerovo, 650002, Russia.

出版信息

Sovrem Tekhnologii Med. 2024;16(5):18-25. doi: 10.17691/stm2024.16.5.02. Epub 2024 Oct 30.

DOI:10.17691/stm2024.16.5.02
PMID:39897070
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11784878/
Abstract

UNLABELLED

There is a growing need for synthetic small-diameter vascular grafts (<6 mm) for bypass surgery since the majority of currently developed products have demonstrated unacceptable high frequency of thrombosis in preclinical studies. The proprietary composite vascular graft based on a nonwoven polymer with anti-thrombogenic and anti-aneurysm effect and functional activity is aimed at stimulating the formation of vascular neotissue at the implantation site. is to study the surface morphology, physical and mechanical properties of the polycaprolactone/ polyurethane (PCL/PU) small-diameter tissue-engineered vascular graft with growth factors and an anti-thrombogenic surface coating.

MATERIALS AND METHODS

PCL/PU vascular grafts with growth factor mix (GFmix) were manufactured using the electrospinning method. The hydrogel coating containing iloprost (Ilo) and heparin (Hep) was formed by complexation with polyvinylpyrrolidone. The controls were multilayer vascular grafts of similar composition and nonwoven matrices based on 12% PCL and 12% PU. The surface structure was analyzed with the S-3400N scanning electron microscope (Hitachi, Japan). The physical properties of the surface were determined by the wetting angle method. The mechanical properties were evaluated on a Z series universal testing machine (Zwick/ Roell, Germany). Statistical processing of the data was performed using the GraphPad Prism 8 software.

RESULTS

Our new manufacturing technique for the composite PU/PCL/GFmix/ graft has eliminated the problem of graft delamination. The inner surface of the graft consisted of interwined microfibers (1.34 [1.15; 2.28] μm thick), nanofibers (790.0 [604.0; 853.5] nm thick), and interpenetrating pores of different diameters (5.4 [3.8; 8.4] μm). The process of coating formation did not affect the fibers and did not seal the pores, the surface retained its hydrophilic properties (θ=68.61±11.85°). The tensile strength (3.45 [3.17; 4.03] MPa) and Young's modulus (4.88 [3.95; 5.80] MPa) of PU/PCL/GFmix/ grafts were almost similar to the human internal thoracic artery compared to the multilayer analogs. The PU/PCL/GFmix/ grafts were superior to the multilayer PCL/PU/GFmix/ grafts in terms of reduced excessive elasticity (to 118.0 [111.0; 125.0]%; p=0.043).

CONCLUSION

The composite functionalized vascular PU/PCL/GFmix/ grafts have enhanced characteristics and compliance, which, in turn, increases the probability of their high patency in future preclinical studies.

摘要

未标注

由于目前大多数已开发的产品在临床前研究中显示出不可接受的高血栓形成频率,因此对用于旁路手术的合成小直径血管移植物(<6毫米)的需求日益增长。基于具有抗血栓形成、抗动脉瘤作用和功能活性的非织造聚合物的专利复合血管移植物旨在刺激植入部位血管新组织的形成。本研究旨在研究具有生长因子和抗血栓形成表面涂层的聚己内酯/聚氨酯(PCL/PU)小直径组织工程血管移植物的表面形态、物理和机械性能。

材料与方法

采用静电纺丝法制备含生长因子混合物(GFmix)的PCL/PU血管移植物。含伊洛前列素(Ilo)和肝素(Hep)的水凝胶涂层通过与聚乙烯吡咯烷酮络合形成。对照组为组成相似的多层血管移植物和基于12%PCL和12%PU的非织造基质。用S-3400N扫描电子显微镜(日本日立)分析表面结构。通过接触角法测定表面的物理性质。在Z系列万能试验机(德国Zwick/Roell)上评估机械性能。使用GraphPad Prism 8软件对数据进行统计处理。

结果

我们用于复合PU/PCL/GFmix/移植物的新制造技术消除了移植物分层问题。移植物的内表面由交织的微纤维(厚1.34[1.15;2.28]μm)、纳米纤维(厚790.0[604.0;853.5]nm)和不同直径的互穿孔隙(5.4[

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b7ea/11784878/3c9d665b8d97/STM-16-5-02-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b7ea/11784878/deca2b6fa7c1/STM-16-5-02-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b7ea/11784878/cb670c9ca590/STM-16-5-02-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b7ea/11784878/3c9d665b8d97/STM-16-5-02-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b7ea/11784878/deca2b6fa7c1/STM-16-5-02-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b7ea/11784878/cb670c9ca590/STM-16-5-02-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b7ea/11784878/3c9d665b8d97/STM-16-5-02-f3.jpg

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