Construction Of Coatings With Bidirectional Vascular Cell Selectivity On Vascular Stent For Rapid Endothelium Regeneration

According to the 2019 Global Health Assessment Report,Cardiovascular-related diseases(CVDs)are still the number 1 cause of human death.As of now,the main clinical methods for treating CVDs include drug therapy and heart bypass surgical operations and minimally invasive interventional technology,among which percutaneous coronary intervention(PCI)based on vascular stent is the most prominent.A large number of clinical data show that PCI can effectively reduce the mortality rate caused by CVDs.With the continuous development of interventional therapy technology,the market demand for vascular stents continues to expand.Vascular stents have successively experienced the iterative update of Bare Metal Stents(BMS),Drug-eluting Stents(DES)and Bioresorbable Vascular stents(BRS),but the current mainstream clinical application of vascular stents is still DES,especially the second-generation DES.Although the second-generation DES is superior to all previous stent types in reducing the rate of stent restenosis,it also face the challenges of two major clinical complications of late and very late thrombosis(LST&VLST)and in-stent restenosis(ISR).Mechanical damage to the blood vessels caused by vascular stent implanted in vivo,resulting in the abnormal competitive growth of vascular endothelial cells(VEC)and smooth muscle cells(VSMC)at the damaged site,which is the main factor for the high incidence of ISR.Hence,to ensure the long-term function of the stent,the key lies in promoting the regeneration of diseased endovascular cortex and the repair of the diseased vascular intimal tissue at the implantation site of stents.To improve and solve a series of problems such as clinical complications after stent implantation,besides improving the design optimization of stent body and standardize the operation,it is crucial that study the surface modification of the stent material.This technology imparts special functions to the stent surface,in order to reduce the risk of restenosis and late thrombosis of the vascular stent,and improve its biocompatibility.The construction of modified coatings containing catechol groups on the substrate surface has become one of the most important research direction of surface modification.At the same time,to concretize the biological function(such as anticoagulant,anti-inflammatory,rapid endothelialization,etc.)of the modified coating on the substrate surface,often requires a rapid and effective secondary covalent graft on the coating.Click chemistry,as a highly effective and unique anti-interference and strong by-product chemical reaction with little or no by-products,is now widely used in the field of chemical grafting.This thesis designed and synthesized an alkynyl-rich catechol compound(HP-PAM)based on mussel adhesion inspiration and click chemistry.The catechol structure which contained in the compound can make it firmly adhere to the surface of the substrate material,and used one-step dip coating method to construct the alkyne-rich coating,and then graft the high cell-selective Nylon-3(Azide-Nylon-3)molecules through the azide-alkynne click reactions to obtain a highly vascular cell bidirectional selective coating.The above modified coating can not only inhibits the proliferation of SMC,but also non-toxic to EC and even promotes its growth.Rapid endothelial regeneration is expected to solve the problems of restenosis and late thrombosis caused by the mismatch of EC and SMC functions in the current vascular stent application field,and has potential application value.In this paper,fourier transform infrared spectroscopy(FT-IR),ultraviolet spectroscopy(UV-vis),proton nuclear magnetic resonance spectroscopy(~1HNMR),water contact angle(WCA),X-ray photoelectron spectroscopy(XPS)and other characterization methods were used to verify the rich-end alkynyl catechol compound HP-PAM whether was successfully synthesized.And the characterization methods mentioned above is also used to verify whether the rich terminal alkynyl coating HP-PAM and the highly vascular cell bidirectional selective coating poly-DM were successful preparation.The dissipative quartz crystal Microbalance(QCM-D)experiment verifies the actual grafting amount of Azide-Nylon-3 molecules.In vitro vascular cell simulation experiments confirm the high selectivity of coating poly-DM,and in vivo vascular stent implantation experiments show that the modified vascular stent is significantly better than BMS in quickly promoting endothelialization and inhibiting intimal hyperplasia.Meanwhile,the modified vascular stent has no anticoagulant effect,which is confirmed by fibrinogen adhesion experiments,platelet adhesion and activation experiments.But it is also providing a basis for factual exploration for the improvement of the design of subsequent topics.