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聚(L-丙交酯-乙交酯)-聚(1,5-二氧杂环庚烷-2-酮)多嵌段共聚物的合成及抗血小板黏附行为

Synthesis and Antiplatelet Adhesion Behavior of a Poly(L-lactide--glycolide)-Poly(1,5-dioxepan-2-one) Multiblock Copolymer.

作者信息

Jikei Mitsutoshi, Takeda Mao, Kaneda Yoshiki, Kudo Kohei, Tanaka Nozomi, Matsumoto Kazuya, Hikida Masaki, Ueki Shigeharu

机构信息

Department of Materials Engineering, Graduate School of Engineering Science, Akita University, 1-1, Tegatagakuen-machi, Akita-shi, Akita 010-8502, Japan.

Department of Life Science, Graduate School of Engineering Science, Akita University, 1-1, Tegatagakuen-machi, Akita-shi, Akita 010-8502, Japan.

出版信息

ACS Omega. 2021 Oct 13;6(42):27968-27975. doi: 10.1021/acsomega.1c03846. eCollection 2021 Oct 26.

Abstract

Platelet adhesion and denaturation on artificial medical implants induce thrombus formation. In this study, bioabsorbable copolymers composed of poly(l-lactide--glycolide) (PLGA) and poly(1,5-dioxepan-2-one) (PDXO) were synthesized and evaluated for their antiplatelet adhesive properties. The PLGA-PXO multiblock copolymer (PLGA-PDXO MBC) and its random copolymer (PLGA-PDXO RC) showed effective antiplatelet adhesive properties, and the number of adhered platelets was similar to those adhered on poly(2-methoxyethylacrylate), a known antiplatelet adhesive polymer, although a large number of denatured platelets were observed on a PLGA-poly(ε-caprolactone) multiblock copolymer (PLGA-PCL MBC). Using monoclonal antifibrinogen IgG antibodies, we also found that both αC and γ-chains, the binding sites of fibrinogen for platelets, were less exposed on the PLGA-PDXO MBC surface compared to PLGA-PCL MBC. Furthermore, free-standing films of PLGA-PDXO MBC were prepared by casting the polymer solution on glass plates and showed good tensile properties and slow hydrolytic degradation in phosphate-buffered saline (pH = 7.4). We expect that the unique properties of PLGA-PDXO MBC, i.e., antiplatelet adhesive behavior, good tensile strength, and hydrolytic degradation, will pave the way for the development of new bioabsorbable implanting materials suitable for application at blood-contacting sites.

摘要

血小板在人工医用植入物上的黏附与变性会引发血栓形成。在本研究中,合成了由聚(L-丙交酯-乙交酯)(PLGA)和聚(1,5-二氧杂环庚烷-2-酮)(PDXO)组成的生物可吸收共聚物,并对其抗血小板黏附性能进行了评估。PLGA-PXO多嵌段共聚物(PLGA-PDXO MBC)及其无规共聚物(PLGA-PDXO RC)表现出有效的抗血小板黏附性能,黏附的血小板数量与黏附在已知的抗血小板黏附聚合物聚(2-甲氧基乙基丙烯酸酯)上的数量相似,尽管在PLGA-聚(ε-己内酯)多嵌段共聚物(PLGA-PCL MBC)上观察到大量变性血小板。使用单克隆抗纤维蛋白原IgG抗体,我们还发现,与PLGA-PCL MBC相比,纤维蛋白原与血小板结合的αC链和γ链在PLGA-PDXO MBC表面的暴露程度较低。此外,通过将聚合物溶液浇铸在玻璃板上制备了PLGA-PDXO MBC的独立膜,其在磷酸盐缓冲盐水(pH = 7.4)中表现出良好的拉伸性能和缓慢的水解降解。我们期望PLGA-PDXO MBC的独特性能,即抗血小板黏附行为、良好的拉伸强度和水解降解性能,将为开发适用于血液接触部位的新型生物可吸收植入材料铺平道路。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/15a6/8552321/9baed4026a54/ao1c03846_0002.jpg

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