Construction And Performance Of An Anti-coagulation And Anti-infection Double-function PU Vascular Stent

At present,cardiovascular diseases are threatening human health.The main clinical manifestations of cardiovascular diseases are stenosis and blockage.In clinic,vascular stent intervention has become the main treatment of cardiovascular diseases.However,there are three challenges in the clinical application of vascular stents,including precision medicine,thrombosis mediated by vascular stent implantation and infection.In this study,we used a combination way of 3D printing and coating technology to prepare double-functional polyurethane vascular stents,aiming at preventing thrombosis induced by vascular stent implantation and infection.Firstly,polyurethane vascular stent was prepared by 3D printing technology using polyurethane as ink material.Secondly,zein nanospheres loaded with zinc oxide nanoparticles were sprayed on the surface of polyurethane vascular stent.Finally,heparin was loaded on the double-function polyurethane vascular stent by immersion method.Transmission electron microscopy,scanning electron microscopy,X-ray photoelectron spectroscopy,hydrostatic Contact Angle and X-ray diffraction showed that zinc oxide nanoparticles and heparin were successfully loaded on polyurethane vascular stent.Here,zein nanospheres played a key role at providing different drug delivery mechanisms for zinc oxide nanoparticles and heparin of the double-functional polyurethane vascular scaffold.Heparin was completely released within 120 min,and Zn²⁺was released slowly.The cumulative release reached 62.7±5.6%after 9days.The mechanical analysis showed that the tensile strength of the double-functional polyurethane vascular stent was 8.6±0.6 MPa,which was similar to that of human saphenous vein（5.38±0.6 MPa）and umbilical artery（1.65±0.11 MPa）.The results of in vitro cell metabolic activity and live/dead cell staining showed that the metabolic activity of the two groups of double-functional polyurethane vascular scaffolds on endothelial cells was 97.9±3.8%and 87.4±2.3%,both of which were greater than 80%,showing good endothelial cell metabolic activity and no toxicity to cells.Hemolysis test,platelet adhesion test,protein adsorption test and calcification coagulation test showed that the double-functional polyurethane stent had good blood compatibility and antithrombotic activity.Ex vivo intervention experiment of rabbit carotid artery showed that the double-functional polyurethane stent could keep blood vessels unobstructed and maintain blood circulation.The in vitro anti-infection experiments proved that the double-functional polyurethane vascular stent had excellent anti-infection performance.The results of in vivo simulation of infection showed that the CD68 positive area of the bifunctional polyurethane stent was 27.7±0.8%lower than that of the nude polyurethane stent group（34.5±2.1%）at 7 days.The positive area ofα-SMA of the former was 4.1±1.5%lower than that of the latter（34.5±2.1%）,which improved histocompatibility.These results indicate that the double-functional polyurethane vascular stents have good blood compatibility,anti-thrombosis and anti-infection performance,which provides a comprehensive treatment strategy to solve the personalized customization,thrombosis and infection faced by vascular stent implantation at present.