A heparin-rosuvastatin-loaded P(LLA-CL) nanofiber-covered stent inhibits inflammatory smooth-muscle cell viability to reduce in-stent stenosis and thrombosis.

A heparin-rosuvastatin-loaded P(LLA-CL) nanofiber-covered stent inhibits inflammatory smooth-muscle cell viability to reduce in-stent stenosis and thrombosis.
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负载肝素-瑞舒伐他汀的 P(LLA-CL) 纳米纤维覆盖支架可抑制炎症平滑肌细胞活力,从而减少支架内狭窄和血栓形成

DOI:
10.1186/s12951-021-00867-8
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发表时间:
2021-04-29
影响因子:
10.2
通讯作者:
Zhu W
Zhu W
中科院分区:
工程技术1区
文献类型:
--
作者:
Liu Y;Liu P;Song Y;Li S;Shi Y;Quan K;Yu G;Li P;An Q;Zhu W

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An endovascular covered-stent has unique advantages in treating complex intracranial aneurysms; however, in-stent stenosis and late thrombosis have become the main factors affecting the efficacy of covered-stent treatment. Smooth-muscle-cell phenotypic modulation plays an important role in late in-stent stenosis and thrombosis. Here, we determined the efficacy of using covered stents loaded with drugs to inhibit smooth-muscle-cell phenotypic modulation and potentially lower the incidence of long-term complications. Nanofiber-covered stents were prepared using coaxial electrospinning, with the core solution prepared with 15% heparin and 20 µM rosuvastatin solution (400: 100 µL), and the shell solution prepared with 120 mg/mL hexafluoroisopropanol. We established a rabbit carotid-artery aneurysm model, which was treated with covered stents. Angiography and histology were performed to evaluate the therapeutic efficacy and incidence rate of in-stent stenosis and thrombosis. Phenotype, function, and inflammatory factors of smooth-muscle cells were studied to explore the mechanism of rosuvastatin action in smooth-muscle cells. Heparin–rosuvastatin-loaded nanofiber scaffold mats inhibited the proliferation of synthetic smooth-muscle cells, and the nanofiber-covered stent effectively treated aneurysms in the absence of notable in-stent stenosis. Additionally, in vitro experiments showed that rosuvastatin inhibited the smooth-muscle-cell phenotypic modulation of platelet-derived growth factor-BB induction and decreased synthetic smooth-muscle-cell viability, as well as secretion of inflammatory cytokines. Rosuvastatin inhibited the abnormal proliferation of synthetic smooth-muscle cells, and heparin–rosuvastatin-loaded covered stents reduced the incidence of stenosis and late thrombosis, thereby improving the healing rates of stents used for aneurysm treatment. The online version contains supplementary material available at 10.1186/s12951-021-00867-8.
DOI: 10.1016/j.rec.2015.02.028
发表时间: 2015-12-01
影响因子: 5.9
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