Heparin and Vascular Endothelial Growth Factor Loaded Poly(L-lactide-co-caprolactone) Nanofiber Covered Stent-Graft for Aneurysm Treatment

Abstract

Restenosis caused by thrombopoiesis is one of the biggest hinders of endovascular stent-graft used in small-diameter vessels. Rapid endothelialization of the lumen of stent is a promising approach to prevent thrombosis. In this study, we aimed at loading heparin, a potent anticoagulants, and vascular endothelial growth factor (VEGF) into the core of poly(L-lactide-co-caprolactone) nanofiber via emulsion electrospinning. The nanofiber was covered on the stent and applied in the treatment of vascular diseases such as aneurysm. The morphologies of the emulsion electrospun nanofibers and core--shell structure were observed by scanning electron microscope and laser scanning confocal microscope. The release profiles of heparin and VEGF, degradation rate of nanofiber mats and cell proliferation in vitro were investigated. It was found that the release of both heparin and VEGF from the nanofiber lasted for more than 30 days without serious initial burst release. The degradation rate of nanofiber mats containing heparin and VEGF was faster than that of pure PLCL nanofiber mats. Moreover, the released VEGF could promote the proliferation of Pig iliac endothelial cells (PIECs) cultured on the nanofiber mat, which was of great benefit to stent endothelialization. The results of digital subtraction angiography (DSA) follow-up indicated the aneurysm was obliterated by separating the aneurysm dome from the blood circulation and the parent artery kept long-term patency. Results of the study demonstrated that the heparin and VEGF loaded nanofiber could provide an approach to fabricate covered stent-graft with properties of anticoagulation and induction of rapid endothelialization.