Persulfated flavonoids accelerated re-endothelialization and improved blood compatibility for vascular medical implants

Abstract

Drug-eluting stents (DESs) have been used for the treatment of cardiovascular diseases including stenosis. However, in-stent restenosis, thrombosis, and delayed re-endothelialization represent challenges for their clinical applications. Here, we demonstrate a novel work to overcome these limitations through surface modification technology. The cobalt-chromium (Co-Cr) surface was modified with antioxidants such as gallic acid (GA) and rutin (Ru) and the corresponding persulfates derivatives (Le., GAS, and RuS) through a simple conjugation procedure. Various analyses tools such as ATR-FTIR, XPS, water contact angle, SEM, and AFM characterized the functionalized surface. The surface characterization confirmed that the antioxidant and the additional persulfates were successfully bonded to the Co-Cr surface. The results of in vitro endothelial cells proved that the persulfates derivatives showed the highest tendency to get rapid re-endothelialization especially RuS. In addition, it showed inhibition to smooth muscle cells (SMCs) as compared to control Co-Cr substrate. The persulfates modified substrates reduced the amount of adsorbed fibrinogen and albumin with higher stability to fetal bovine serum. Moreover, platelet study also demonstrated that Ru and RuS presented lower platelet adhesion with round shape morphology, whereas the control Co-Cr adhere and activate many platelets with pseudopodium morphology. Moreover, these modification processes did not cause any inflammatory responses. In conclusion, it is believed that the persulfates flavonoids have a great potential in the field of drug-eluting stents and blood contacting medical implants to improve blood compatibility, suppress SMCs, and get rapid re-endothelialization.