Construction and biological function evaluation of a small caliber artificial vascular graft material loaded with copper complexes
Objective To construct a nanofiber small caliber artificial blood vessel material loaded with endogenous nitric oxide donor catalyst copper complexes and evaluate its biological function.Method A copper ion complex(Cu(II)-DTTCT)was synthesized to catalyze the release of nitric oxide(NO)from nitric oxide donors(RSNO)in vivo.The small caliber artificial blood vessel scaffold material was prepared using Cu(II)-DTTCT and a highly biocompatible polymer,polycaprolactone(PCL),as raw materials with precise catalyst dosage and coaxial electrospinning method.Its nitric oxide release,copper ion complex encapsulation efficiency,and cytotoxicity was measured.Male SD rats weighing 250-270 grams were used as in vitro and in vivo evaluation vectors.Its biological function was evaluated using techniques such as arteriovenous shunt(AV shunt),implantation material orthotopic transplantation,in vivo ultrasound examination,body microscopy and scanning electron microscopy observation,and HE staining.Result A small caliber artificial blood vessel scaffold material PCL&Cu(II)-DTTCT with a core-shell structure was constructed with catalyst Cu(II)-DTTCT and PCL as the core and PCL as the shell.PCL&Cu(II)-DTTCT showed no significant sudden release of nitric oxide at the detected time.The encapsulation efficiency of copper ion complex was 91.60%.The cytotoxicity of the fiber membrane loaded with copper ion complex PCL&Cu(II)-DTTCT in the core layer showed no significant difference compared to the control group(PCL).After one hour of AV shunt test in vitro,deposition and platelet adhesion were observed on the inner wall of PCL material in the control group under a stereomicroscope.The inner wall of PCL&Cu(II)-DTTCT material in the experimental group was relatively clean and smooth with no obvious thrombi.Under scanning electron microscopy,a large amount of platelet adhesion was observed in the control group PCL,while there were few platelets on the experimental group PCL&Cu(II)-DTTCT material,and the artificial vascular fiber structure was clearly visible.The blood vessels were all unobstructed by ultrasound and there was no death due to vascular occlusion in the PCL control group and the PCL&Cu(II)-DTTCT experimental group after the orthotopic transplantation of artificial blood vessels at 2 weeks,1 month,3 months,and 6 months.One month after surgery,the PCL&Cu(II)-DTTCT tubes in the experimental group had uniform walls and clean lumens under a stereomicroscope with no obvious thrombi.In the control group,there were some microthrombosis due to the infiltration of red blood cells on the surface.The surface of the two groups'official cavities had been completely covered with scanning electron microscopy.Platelets were visible in the PCL control group,while no significant platelet imaging was observed in the PCL&Cu(II)-DTTCT experimental group.A layer of regenerated tissue was observed in the lumen of the vascular stents in the control and experimental groups by HE staining to analyze the tissue regeneration of vascular stents.The thickness of the newly formed tissue in the experimental group was significantly higher than that in the control group.The adhesion of nuclear cells in the experimental group was higher than that in the control group.Conclusion The constructed nanofiber small caliber artificial blood vessel material PCL&Cu(II)-DTTCT loaded with endogenous nitric oxide donor catalyst copper complexes can promote the sustained release of nitric oxide,simulate the release of nitric oxide from natural vascular endothelial cells,exert the physiological function of inhibiting platelet adhesion,inhibit thrombosis formation and early restenosis,and promote tissue regeneration in the early stage.
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