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

Autor: Yingjun Liu, Peixi Liu, Yaying Song, Sichen Li, Yuan Shi, Kai Quan, Guo Yu, Peiliang Li, Qingzhu An, Wei Zhu
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Zdroj: Journal of Nanobiotechnology, Vol 19, Iss 1, Pp 1-17 (2021)
Druh dokumentu: article
ISSN: 1477-3155
DOI: 10.1186/s12951-021-00867-8
Popis: Abstract Background 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. Methods 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. Result 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. Conclusion 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. Graphic abstract
Databáze: Directory of Open Access Journals
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