Endothelium-mimicking Coating With Bidirectional Vascular Cell Selectivity For Modification Of Vascular Stents

The cardiovascular disease is the most life threatening disease in the world today and is mainly caused by atherosclerosis.The main treatment modalities for this type of cardiovascular disease are drug therapy,drug balloon therapy,vascular stent intervention and vascular bypass surgery.When patients undergo vascular stent intervention,there is a risk of delayed endothelialisation of the stent surface due to inadequate reendothelialisation of the stent,which can lead to endothelial hyperplasia and restenosis of the diseased vessel.The fundamental solution to these problems is therefore to achieve endothelial regeneration and endothelial repair.To improve and solve problems such as clinical complications arising after stent implantation,cardiovascular stent surfaces are modified to confer good biocompatibility,bi-directional vascular cell selectivity and other functions to enable rapid endothelial layer regeneration on the surface of the stent after intervention and to inhibit endothelial overgrowth.Mussel-inspired polydopamine coating technology and efficient,bond-strengthening click chemistry are used in many areas of surface modification,chemical grafting and more.Research has identified a nylon-3 polymer that both promotes endothelial cell growth and inhibits smooth muscle cell proliferation,but the molecule does not regulate inflammation,anticoagulation or antithrombotic functions.Another studies have shown that Cu²⁺catalyzes the release of NO,which inhibits coagulation,regulates the phenotype of smooth muscle and promotes self-repair of the vascular endothelium.Based on this,this study is based on mussel inspiration and click chemistry.A firmly adherent polydopamine（PDA）coating is prepared on the base material substrate surface of a 316L stainless steel bare metal support.The PDA surface was dissolved-polymerised and reassembled using alkaline DOTA@Cu-PAa solution to obtain a Cu-DOAM conversion coating containing catalytic release of NO and a large number of chemically graftable amine groups.The Cu-DOAM conversion coating was then amide-grafted with pentinoic acid（4-PA）,and finally,nylon-3,which is bidirectionally selective for vascular cells,was grafted onto the coating by a click reaction to obtain a functional endothelial mimetic Cu-DOAM&Nylon coating with bidirectional vascular cell selectivity.In this study,the hydrophobicity,composition and structure of the coatings were analyzed using fourier transform infrared（FTIR）,raman spectroscopy（RAMAN）,X-ray photoelectron spectroscopy（XPS）,water contact angle measurement（WCA）,dissipative quartz crystal microbalance（QCM-D）and elliptical polarization spectroscopy,etc.The NO catalytic release rate of the coatings was evaluated by chemiluminescence NO analyzer.The cytocompatibility of the coating was tested by the adhesion and proliferation behaviour of various cells on the surface of the coating.Evaluation of the haemocompatibility of the coating by haemolysis rate,adsorption and activation of fibrinogen and adhesion and activation of platelets.The anti-coagulant properties of the coating were verified by semi-in vivo animal blood circulation experiments.The results of FTIR,RAMAN,XPS,WCA,QCM-D and ellipsometric polarisation spectroscopy show that the Cu-DOAM conversion coating based on the reassembled PDA coating was successfully prepared,and the amine group on the surface of the coating was successfully amidated with pentinoic acid,and finally the nylon-3 was successfully grafted by the click reaction,the grafting amount was 171.4 ng/cm²,Cu-DOAM&Nylon coating was successfully prepared.The results of cellular experiment,haemolysis rate experiment,fibrinogen experiment,platelet experiment and semi-in vivo animal blood experiment show that the modified substrate has bidirectional vascular cell selectivity,it can effectively promote the growth and migration of endothelial cells and inhibit the excessive proliferation of smooth muscle;effectively reduce the adsorption and activation of fibrinogen,significantly reduce the adhesion and activation of platelets on the surface;the results of animal assay studies further confirm that this functional coating exhibits excellent anticoagulant and antithrombotic properties.This endothelial functional bionic coating with a high degree of vascular cell selectivity is reported for the first time,is easy to handle and the functional coating has potential applications in the field of functional modification of stent surfaces.