Study Of The Electrospun PCL-PIBMD Artificial Vascular Grafts Modified With Gene Complexes

At present,implantation of artificial vascular grafts is one of the main treatment strategies for the cardiovascular diseases.However,due to the lack of a living functional layer of endothelial cells(ECs),artificial vascular grafts,especially small-diameter artificial vascular grafts,usually encounter low long-term patency and restenosis,hence limiting their clinical application eventually.Nevertheless,it has been proved that rapid endothelialization of artificial vascular grafts benefits to address these problems.With the development of gene therapy,using gene transfection technology which helps for promoting the proliferation of ECs attracts more and more attention.In this study,artificial vascular meshes loaded with targeted gene complexes which contributed to the proliferation of ECs were farbricated by electrospinning and electrospraying technique.The main results of this study are as follows:1.Electrospun fibrous meshes were successfully prepared by mutiblock copolymers consisting of poly(?-caprolactone)(PCL)and poly(isobutyl-morpholine-2,5-dione)(PIBMD)segments.Then,the targeted polycationic gene carriers(MPs)and gene complexes(MPs-pZNF580)were used to modify electrospun PCL-PIBMD fibrous meshes via electrospraying techniques.With the introduction of MPs and MPs-pZNF580,the fiber diameters and mechanical properties of PCL-PIBMD fibrous meshes showed no significant change.However,the hydrophilicity of modified fibrous meshes was slightly improved.Besides,the platelet adhesion tests indicated PCL-PIBMD/MPs and PCL-PIBMD/MPs-pZNF580 fibrous meshes possessed better hemocompatibility compared to PCL-PIBMD fibrous meshes.The relative cell number and cell density of PCL-PIBMD/MPs-pZNF580 was 121.5±1.2% and 749 cells/mm2 respectively after 7 days of culture by MTT assay and cell fluorescence assays,which confirmed that PCLPIBMD/MPs-pZNF580 fibrous meshes could obviously enhance the proliferation of endothelial cells(EA.hy926 cells).2.The tissue compatibility of PCL-PIBMD fibrous meshes was clarified after subcutaneous implantation into Sprague-Dawley rats.The results showed the acute inflammatory reaction of PCL-PIBMD/MPs-pZNF580 was slightest compared to PCLPIBMD fibrous meshes and PCL-PIBMD/MPs-pZNF580 fibrous meshes when the tissues contact with the various fibrous meshes.3.The tubular grafts composed of polycarbonate polyurethane(PCU)(out layer)and PCL-PIBMD/MPs-pZNF580(inner layer)was prepared using multi-layering electrospinning technique.The compound grafts implanted into the rabbit carotid artery showed good patency during the experimental period,which indicated the great potential in cardiovascular tissue engineering.