Construction Of Hemodialysis Biological Vessels With Human-Derived ECM Combining PCL-PU Fiber Scaffold And The Study On Its Regeneration Process

Background:Artificial arteriovenous fistula is widely used in hemodialysis treatment of renal failure patients,but compared with autologous arteriovenous fistula,its flexibility and compliance are limited,and it cannot tolerate repeated puncture.Moreover,artificial vessels are not easy to match with anastomotic vessels,and the infection rate is high,often accompanied by stenosis and thrombosis.The ideal artificial blood vessel for dialysis should mimic the composition and structure of the human artery,which relies mainly on the extracellular matrix(ECM)of the artery for maintenance.Clinically,it is difficult to obtain human ECM;Heterogeneic ECM,although abundant in source,has potential antigenicity.Some studies have shown that patients with hepatitis B have cirrhosis due to continuous activation of human hepatic stellate cells(HSCs)by hepatitis B virus(HBV),resulting in excessive secretion of ECM.On the other hand,mechanical stimulation can promote the secretion and shaping of ECM,which provides ideas for the development of this study.Methods:In this study,a human extracellular matrixpolycaprolactone-polyurethane(ECM-PCL-PU)complex biological vessel was developed as dialysis access.The PU dense polymer nanofiber layer with anticoagulant effect was obtained by electrostatic spinning,and the porous scaffold was obtained by PCL foaming on its surface.Then LX2 cells which stably transfected HBX(HBX-LX2)were planted to secrete human ECM.The blood vessels were placed in a reactor,ECM was molded under mechanical stress,and then the cell components were removed to obtain human nano ECM-PCL-PU composite blood vessels.The blood vessel was transplanted to connect the carotid vein and carotid vein of rabbits.The blood vessel and blood flow status,migration and infiltration of immune cells,and dynamic changes of ECM components of blood vessels in different phases were detected to explore the regeneration and remodeling process of the blood vessel.Results:The ECM-PCL-PU composite blood vessel prepared in this study contains ECM secreted by human cells,which has the natural structure and characteristics of living blood vessels,and is conducive to the repeated puncture resistance of the composite blood vessel during dialysis.At the same time,it is similar to the elasticity and compliance of natural blood vessels.It still maintains the tubular structure when bent into U-shaped loops and is not easy to be discounted.After implantation in rabbits,the experimental group(ECM-PCL-PU composite vascular group)had better blood flow patency,tissue fusion,tensile resistance and extracellular matrix regeneration than the control group(simple PCL-PU scaffold group).Conclusion:The ECM-PCL-PU composite biological vessel developed in this study is expected to overcome the shortcomings of artificial vessels currently used in clinical practice,and provide a new method and idea for the preparation of dialysis vessels.