Construction Of Dual-Functionalization Vascular Devices:the Synergy Of NO Generation And EPCs Recruitment

Vascular stent implantation as the most effective treatment has been used in the clinical treatment of cardiovascular diseases,saving many patients with cardiovascular diseases.However,the frequent occurrence of late thrombosis and the high rate of in-stent restenosis still cause widespread concern.After stent implantation,a series of pathological reactions such as coagulation,hyperplasia and inflammation will be triggered,which will greatly delay the surface of the stent and lead to the occurrence of late thrombosis and in-stent restenosis.Healthy vascular endothelium is a natural barrier to prevent thrombosis.It releases nitric oxide(NO)molecule through endothelial cells to achieve the effect of anticoagulation,antiproliferation and anti-inflammatory.Therefore,in order to completely eradicate the two major clinical complications of late thrombosis and stent internal stenosis,the ideal stent surface needs to have the ability to promote vascular repair and re-endothelialization of the stent surface.Based on this,we constructed a surface that can continuously release NO and capture endogenous EPCs,so as to promote the integrity and functional recovery of newborn endodermis and achieve long-term effective cure.Herein,modified surfaces were constructed based on Mussel-inspired Chemistry and novel Copper-free Click Chemistry.DOPA molecules labeled with azide group were introduced into the surface of titanium oxide film coated materials through stable coordination between phenolic hydroxyl groups and unsaturated metal ions.Copper-free Click Reaction was used to graft two cyclooctyne biomolecules with NO catalytic release and endothelial progenitor cell(EPCs)capture functions.The novel scaffold surface constructed in this paper differs from the previous scaffold surface in that it simply anticoagulates and promotes endothelialization.Its innovation is that it uses a multi-molecule one-step grafting method,while achieving anticoagulation,a layer of endothelium is formed by capturing the EPCs of the body's own,which is not recognized by the immune mechanism.It effectively ensures the integrity and functional recovery of the damaged endothelium in a short period of time,and achieves the purpose of completely curing the diseased tissue.The results of XPS and QCM in this paper indicate the successful construction of(DOPA)4-N3@DBCO-SeCA/DBCO-TPS on the surface of the material.The in vitro biocompatibility evaluation results show that the materials modified by this experiment have good cytocompatibility and anticoagulant properties,can effectively inhibit the SMCs adhesion,proliferation and migration,which was more conducive to the growth of ECs in the competitive environment between ECs and SMCs.The results of the in vivo anticoagulation experiment further demonstrate that the modified surface has good antithrombotic ability.The results of EPCs capture experiments also significantly indicate that the modified surface has high binding and high specificity of EPCs.Result of stent implantation in vivo also showed a more intuitive and clear indication that the modified stent has good anti-proliferative,antithrombotic and anti-stent restenosis ability,and can quickly form a complete,uniform and dense endothelial cell layer on the surface of the stent by capturing EPCs in the autologous blood in a short time.This paper provides new strategies and theoretical support for the complete cure of cardiovascular diseases and the eradication of two major clinical complications of in-stent restenosis and late thrombosis.