Polyphenol-Amine Inspiration Chemistry To Construct Endothelial Functional Bionic Vascular Scaffold

Cardiovascular disease?CVDs?is the most common cause of death in the world.Interventional therapy for vascular stent is a widely used method for the treatment of cardiovascular diseases.It is a minimally invasive therapy that is very effective in early clinical applications.However,the bare metal stents?BMS?that lack of biocompatibility can lead to postoperative complications such as restenosis and late thrombosis.Although drug-eluting stent?des?can inhibit the proliferation of smooth muscle and reduces the incidence of restenosis by releasing drugs.But the use of antiproliferative drugs leads to delayed endothelialization and increases the risk of late-stage thrombosis.Therefore,it is extremely urgent to improve the biocompatibility of vascular stents and reduce the incidence of postoperative complications such as restenosis and late thrombosis.It has been found that it is an effective way to improve the biocompatibility of vascular scaffolds by using surface modification technique to modify the surface of stent.In this paper,Based on the synergistic adhesion effect of phenol-amine chemistry,a novel amino-rich PPAMCA coating was prepared by using the synthetic mussel-like adhesion molecule?PAMCA?.The biomimetic coating of Hep-Cu^II endothelium was constructed by immobilization Hep and chelating the DOTA molecule of Cu^II,andIt has the function of catalytic release of NO.NO not only regulate the proliferation of endothelial cells and inhibit intimal proliferation,but also is an excellent molecule to inhibit platelet polymerization and adhesion.Heparin inhibits fibrin production in the clotting cascade.The two-way anticoagulant mechanism of NO and heparin molecules complement each other,and the complementary synergistic effect has more excellent anticoagulant and anti-proliferative effects.These two biomolecules are immobilized to the surface of the polymer coating to make it functionally closer to the endothelial layer,resulting in a highly biomimetic anti-coagulation coating.The coating imparts biofunctionality to the bare basal vascular scaffold for superior biocompatibility while achieving rapid endothelialization,for the purpose of treating atherosclerotic lesions and preventing restenosis.In this paper,the successful preparation of PPAMCA coating and Hep-Cu^II endothelial biomimetic coating was verified by FTIR,UV spectroscopy,H-NMR,XPS,water contact angle and other material characterization methods.The fixed amount of Hep and Cu^III on the surface of the material was verified by QCM-D experiment.NO catalytic release rate experiment and NO release stability experiment screening of Hep-Cu^III coating suitable process ratio,and the balloon expansion experiments demonstrate the mechanical properties of Hep-Cu^II endothelium biomimetic coating,which can meet the long-term requirements of cardiovascular stents.Both in vitro blood tests and half-body blood circulation experiments have verified that Hep-Cu^II endothelium biomimetic coating can effectively inhibit fibrinogen activation and platelet activation and adhesion,and has excellent anticoagulant properties.The results of cell experiments show that Hep-Cu^III coating can significantly promote the proliferation and adhesion of endothelial cells,inhibit the excessive proliferation of smooth muscle,not only has good cell compatibility,but also can regulate cell growth behavior,and achieve new endothelial layer after stent implantation.In vivo stent implantation experiments have demonstrated that Hep-Cu^II coated stents have obvious advantages and effects compared to bare metal stents,it can promote endothelial regeneration,not only reduce neointimal area and restenosis rate,but also reduce and prevent stenting complications such as restenosis.it provide a guiding significance in the clinical application of the stent.