Inhibition of in-stent restenosis after graphene oxide double-layer drug coating with good biocompatibility.

In this study, we designed a double layer-coated vascular stent of 316L stainless steel using an ultrasonic spray system to achieve both antiproliferation and antithrombosis. The coating included an inner layer of graphene oxide (GO) loaded with docetaxel (DTX) and an outer layer of carboxymethyl chitosan (CMC) loaded with heparin (Hep). The coated surface was uniform without aggregation and shedding phenomena before and after stent expanded. The coating treatment was able to inhibit the adhesion and activation of platelets and the proliferation and migration of smooth muscle cells, indicating the excellent biocompatibility and antiproliferation ability. The toxicity tests showed that the GO/DTX and CMC/Hep coating did not cause deformity and organ abnormalities in zebrafish under stereomicroscope. The stents with GO double-layer coating were safe and could effectively prevent thrombosis and in-stent restenosis after the implantation into rabbit carotid arteries for 4-12 weeks.

An asymmetrical dual coating on the stent prepared by ultrasonic atomization.

This study aims to design an asymmetric dual coating (ADC) on the stent by ultrasonic atomization to solve the problem of delayed endothelialization and late or very late stent thrombosis which caused by drug eluting stent (DES) with symmetric coating. Chitosan-loaded monoclonal platelet glycoprotein IIIa receptor antibody SZ-21 coating (CSC) was sprayed on inner surface of stents, and outer surface was sprayed CSC and poly(lactic-co-glycolic acid) (PLGA) loaded with docetaxel (DTX) coating (PDC). The coated surface was uniform without aggregation and no shedding phenomenon either before or after stent expanded. Fluorescence labeling has confirmed that the coating has an asymmetric structure. The cumulative release for SZ-21 and DTX was 40.11% and 27.22% within first 24 h, then DTX became the major released drug from 24 h to 7 d, after released for 28 d about 40% of the SZ-21 and 50% DTX still remained on the coated stent. It achieved that ADC can inhibit thrombosis at earlier period and inhibit vascular smooth muscle cells (VSMCs) proliferation at later period. And that ADC has good hemocompatibility and can significantly inhibit VSMCs proliferation. Finally, 4 and 12 weeks after the stent with ADC implanted into rabbit carotid arteries, it showed that the stent with ADC was safe and could effectively prevent thrombosis and in-stent restenosis. © 2018 Wiley Periodicals, Inc. J. Biomed. Mater. Res. Part B, 2018. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B: 825-837, 2019.

[Endothelial injury and its repair strategies after intravascular stents implantation].

Coronary atherosclerotic heart disease is a serious threat to human life and health. In recent years, the main treatment for it is to implant the intravascular stent into the lesion to support blood vessels and reconstruct blood supply. However, a large number of experimental results showed that mechanical injury and anti-proliferative drugs caused great damage after stent implantation, and increased in-stent restenosis and late thrombosis risk. Thus, maintaining the integrity and normal function of the endothelium can significantly reduce the rate of thrombosis and restenosis. Stem cell mobilization, homing, differentiation and proliferation are the main mechanisms of endothelial repair after vascular stent implantation. Vascular factor and mechanical microenvironmental changes in implanted sites have a certain effect on re-endothelialization. In this paper, the process of injury caused by stent implantation, the repair mechanism after injury and its influencing factors are expounded in detail. And repairing strategies are analyzed and summarized. This review provides a reference for overcoming the in-stent restenosis, endothelialization delay and late thrombosis during the interventional treatment, as well as for designing drug-eluting and biodegradation stents.