| With the development of society,people's living standards continue to improve,although more and more diseases are more likely to be cured,cardiovascular disease still have the potential to affect human health.Coronary heart disease is a highly dangerous cardiovascular disease,and atherosclerosis is the basic cause of coronary heart disease.Interventional therapy is the most commonly used method in the treatment of cardiovascular diseases.Vascular stents are the necessary medical implants for clinical applications of interventional therapy.The drug-eluting stent consists of a bare metal stent,a surface coating,and a loaded drug.It is the most widely used therapy method in clinic because of its safety and effectiveness.Traditional drug-eluting stents can only passively release drugs with the corrosion of surface coatings or the concentration diffusion of loaded drugs,and can not control the release amount and release rate of the drug,which may cause over-treatment or inadequate treatment,this can lead to restenosis in the stent,late thrombosis and other side effects.In order to safely and effectively prevent the occurrence of restenosis in the stent to restore and maintain vascular homeostasis,an effective means is to modify the surface coating to improve the biocompatibility and surface multifunctionality of the implanted device surface.In this study,we aimed to construct a pH-responsive coating that can regulate the release of drugs in the low-pH and high-oxidation stress environment of atherosclerotic inflammatory areas,and manufactured the drug ACS14.Firstly,the chitosan and hyaluronic acid are functionalized by using the catechol group,and the modified chitosan and hyaluronic acid are deposited by layer self-assembly in the polydopamine with the stainless steel sheet as the substrate,and loading the drug ACS14.The assembly process of the coating was tested by QCM-D technology and the thickness of the coating was calculated.Scanning electron microscopy(SEM)was used to observe the surface morphology of the drug-loaded coating prepared with different concentrations of ACS14 and the uniformity of the coating after loading the drug.The water contact angle of the drug-loaded coatings prepared with different concentrations of ACS14 was measured to indirectly reflect whether the drug was successfully loaded.The X-ray photoelectron spectroscopy was used to test the element content of drug-loaded coatings prepared with different concentrations of ACS14,and the high-resolution spectrum of S elements,which directly verified the successful loading of drugs at different concentrations.The coatings prepared with different concentrations of ACS14 were immersed in different pH PBS solutions to explore the drug release law of the drug-loaded coating under different pH conditions,and the pH responsiveness of the drug-loaded coating was verified.In vitro cell culture and blood compatibility experiments were performed with drug-loaded coatings prepared at different concentrations of ACS14.To study its effects on endothelial cell activity and NO release;effects on the activity and proliferation of smooth muscle cells;effects on the activity and proliferation of macrophages and the secretion of the anti-inflammatory factor interleukin-10 and inflammatory factor TNF-? in macrophages;effects of platelet adhesion and activation,fibrinogen adhesion and denaturation,and hemolysis experiments.The drug-loaded coating prepared with different concentrations of ACS14 was deposited on the surface of stainless steel filaments and implanted into the abdominal aorta of SD rats for one month.After taking out the samples,HE staining,OPN,?-SMA,TNF-? and other immunofluorescence staining were performed.The effects of drug-loaded coatings prepared with different concentrations of ACS14 on the phenotype of smooth muscle,and inflammatory factors of abdominal aorta in rats were studied.The results showed that the drug-loaded coatings prepared with different concentrations of ACS14 contained C,N,O,S elements,and the content of S element increased with increasing drug loading concentration.And the release amount of the drug in the PBS solution of pH=6.5 was greater than the release amount of the drug in the PBS solution of pH=7.4.Compared with the coatings with different drug concentrations,the coating with the drug concentration of 100?mol/L had the best value-added effect on endothelial cells,the highest cell activity,and the The largest amount of NO was released.The drug-loaded coating of this concentration has a good effect on inhibiting the proliferation of macrophages and inhibiting the proliferation and activity of smooth muscle cells.Platelets adhered minimally on the surface of the drug at a concentration of 10 ?mol/L,and there was almost no activation.From the results of adhesion and denaturation of fibrinogen,it was found that fibrinogen adhesion and denaturation were minimal when the coating loading concentration was 10 ?mol/L.The results of the abdominal aortic implantation of SD rats show that the implant site of the sample prepared with 100 ?mol/L of ACS14 had the smallest neointima area,that of the SS group had the largest neointima area,and that the sample prepared with 100?mol/L of ACS14 had the most obvious anti-inflammatory and inhibitory effect on the proliferation of smooth muscle.The pH-responsive drug-loaded coating prepared in this study can be applied to the surface of vascular interventional instruments to achieve targeted treatment of diseased blood vessels,thereby effectively ensuring the effectiveness and safety of the application of the interventional device. |
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