Heparin- and Rosuvastatin- loaded Poly(L-lactide-co-caprolactone) Nanofiber Aneurysm Covered Stent Inhibits Inflammatory Smooth Muscle Cell in Reducing in-stent Stenosis and Thrombosis

Abstract

Background: 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. Thus, covered stents loaded with drugs that can inhibit smooth-muscle-cell phenotypic modulation may lower the incidence of long-term complications. Methods: Nanofiber covered stents were prepared using coaxial electrospinning. A rabbit-carotid-artery aneurysm model was established and 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 in smooth-muscle cells. Result: Heparin–rosuvastatin-loaded nanofiber scaffolds inhibited the proliferation of synthetic smooth-muscle cells. Heparin–rosuvastatin-loaded nanofiber covered stent effectively treated aneurysms without showing any notable in-stent stenosis. In vitro experiments showed that rosuvastatin could inhibit the smooth muscle cell phenotypic modulation of platelet-derived growth factor-BB induction. The inflammatory cytokines secretion and cell viability were inhibited after rosuvastatin treatment.Conclusion: Rosuvastatin could inhibit the abnormal proliferation of synthetic smooth-muscle cells. Heparin–rosuvastatin-loaded covered stents could reduce the incidence of stenosis and late thrombosis and improve the healing rates of stents used for aneurysm treatment.