Promoting vascular healing using nanofibrous ticagrelor-eluting stents

Abstract

ObjectiveThe current treatment of atherosclerotic coronary heart disease with limus-eluting stents can lead to incomplete endothelialization and substantial impairment of arterial healing relative to treatment with bare-metal stents. The sustained and local delivery of ticagrelor, a reversibly binding P2Y12 receptor inhibitor, using hybrid biodegradable nanofibers/stents, was developed to reduce neointimal formation and endothelial dysfunction.MethodsIn this investigation, a solution of ticagrelor, poly(D,L)-lactide-co-glycolide, and hexafluoro isopropanol was electrospun to fabricate ticagrelor-eluting nanofibrous drug-eluting stents. The in vitro and in vivo ticagrelor concentrations were measured using a high-performance liquid chromatography assay. The effectiveness of ticagrelor-eluting stents was examined relative to that of sirolimus-eluting stents.ResultsAdequate ticagrelor levels were detected for four weeks in vitro. Less HES5-positive labeling was found near the ticagrelor-eluting stented vessels (0.33±0.12) than close to the sirolimus-eluting stented vessels (0.57±0.15) (p<0.05). Four weeks after deployment, the ticagrelor-eluting stent also exhibited an up-regulated local expression of SOD1 in the stenting area (p<0.001). The ticagrelor-eluting stent substantially preserved endothelial function and re-endothelialization, minimized inflammatory responses, and inhibited neointimal hyperplasia.ConclusionTicagrelor-eluting stents may provide an alternative route for treating patients at a high risk of bleeding to preserve endothelial recovery and to reduce smooth muscle proliferation.

First Experience of Three Neurovascular Centers With the p64MW-HPC, a Low-Profile Flow Diverter Designed for Proximal Cerebral Vessels With Antithrombotic Coating

“…A growing number of ex vivo and clinical studies in this regard indicate that the currently used P2Y12-receptor antagonists, i.e., clopidogrel, prasugrel, and ticagrelor, have a very different effect on injury-repair process that immediately begins after stenting ( 47 ). The latter anti-platelet drug reduces neo-intimal hyperplasia together with the local inflammatory response and excessive proliferation of smooth muscle cell proliferation while preserving re-endothelialization ( 48 ). Schnorbus et al compared the three P2Y12 anti-aggregants and postulated that prasugrel is associated with improved endothelial function, stronger platelet inhibition, and a lower inflammatory response compared to ticagrelor and clopidogrel ( 49 ).…”

Nanostructured Titanium for Improved Endothelial Biocompatibility and Reduced Platelet Adhesion in Stent Applications

“…The water contact angle was the only parameter affected by the QR coating, and this decrease was expected due to the presence of the biomolecule on the implant surface. The use of a coating that is covalently linked to the surface, as demonstrated by FTIR spectroscopy and XPS in previous studies [18,19], could provide an alternative to the use of a polymer, which is considered as one of the leading causes of late stent thrombosis in DES [8,9]. Similar to previous reports [19,35], QR coated surfaces were also biocompatible on HUVEC cells, and remarkably showed higher metabolic activity in all evaluated time points, similar to other studies with mesenchymal stem cells [18,19].…”

“…Drug eluting stents (DESs) are used to inhibit the proliferation of smooth muscle cells, decreasing the risk of in-stent restenosis by the delivery of an appropriate concentration of an effective agent locally without systemic toxicity [7]. Usually, this controlled liberation of the therapeutic agent is achieved due to the use of a polymer coating; however, there are some complications associated to the use of polymers, considered as one of the leading causes of late stent thrombosis [8,9]. Thus, the use of a nanostructured surface could provide an alternative for the application of the stent coating without the need of using a polymer.…”

Recent advance in treatment of atherosclerosis: Key targets and plaque-positioned delivery strategies

“…More than affecting platelet, the ticagrelor eluting stents preserves endothelial recovery and favors suppressive smooth muscle proliferation. 294 The drug release profile largely determines the overall performance of stents in a variety of evaluation models. 291 Polymers, synthetic or biological polymers, acting as versatile basal layers demanding to provide good biocompatibility (blood or tissue), generally are utilized to incorporate pharmacologic agents for mediating drug release behavior, covering poly(ethylene-co-vinylacetate), poly(n-butylmethacrylate), poly(styrene-b-isobutylene-b-styrene) fluoropolymer, phosphorylcholine, poly(lactic acid) (PLA), and poly(lactic-co-glycolic acid) (PLGA).…”