The Preparation, Characterization And Biocompatibility Study Of Heparin-Loaded Core-Shell Coaxial Electrospun Nanofibers

To fabricate small-caliber vascular scaffold has been the hot spot and difficulty of vascular tissue engineering and regenerative medical research.The ideal small-caliber vascular scaffold should have good biocompatibility and antithrombogenicity.In the kidney dialysis and blood storage area,to prevent blood coagulation is also unavoidable.Heparin is a natural anticoagulant in the body and extend blood coagulation time in vitro and in vivo.Electrospinning is an efficient technology for fabricating ultrafine fibers,enabling the polymer solution or melt with charge to jet in the electrostatic field.Many natural biological materials and polymer can be fabricated into ultrafine fibers or special core-shell structure fibers by this method,and the vascular grafts which are composed of those kinds of fibers have high surface area to volume ratio,high porosity and three-dimensional network structure.Coaxial electrospinning is widely used in the preparation of "core-shell" nanofibers and have large range of application prospect in the biomedical and other fields.Using coaxial electrospinning technology to prepare small-caliber vascular scaffold with P(LLA-CL)(75:25) as shell layer,and heparin as core layer was studied in this paper.SEM,TEM,FTIR and contact angle demonstrated systematically the morphology of the P(LLA-CL) / Heparin nanofiber film,the fiber diameter distribution,and related properties.At 37℃in the PBS Solutions heparin was released from coaxial electrospinning nanofibers with different heparin concentration,and the heparin-release behavior was given.SEM photos of nanofibers after heparin releasing was also shown in the paper.The toluidine blue method to determine amout of heparin,i.e.the standard curve of heparin was analysed which turned out that this mothod only applies to low-concentration;heparin solution of high concentration must be diluted.The study also tested the biocompatibility of P (LLA-CL) / heparin coaxial electrospinning nanofibers through haemolytic experiment,recalcification time,blood clotting time,compared with the results of P (LLA-CL) electrospinning nanofibers.Piatelet adhesion experiment results showed that:heparin-load P(LLA-CL) coaxial electrospinning nanofibers have good blood compatibility.Heparin plays a inhibited role on the fibroblast cells.Through fibroblast experimental,it was detected that P(LLA-CL) / heparin coaxial electrospinning nanofibers can preserve the activity of heparin.Meanwhile,vascular scaffold was produced with inner composed of core-shell P(LLA-CL)/heparin fibers by coaxial electrospinning and the elastic P(LLA-CL)(75:25) fibers as the outer part through the rotational Stainless steel bar as the fiber receiver.Its mechanical properties was tested and through the vascular graft technology in experimental animals Beagle dogs,the pure P(LLA-CL) electrospun fibers and P(LLA-CL) / heparin coaxial electrospun fibers were compared to check the smooth condition.The biocompatibility and antithrombogenicity of P(LLA-CL) / heparin coaxial electrospun nanofibers as an inner of compound small-caliber vascular scaffold was meatured,as well.The results show that heparin-loaded P(LLA-CL) coaxial electrospun nanofibers have good mechanical properties,the core layer drug delivery behavior, antithrombogenicity and biocompatibility.Coaxial electrospinning technology retains core layer heparin's activity.P(LLA-CL) / heparin coaxial electrospun tube fibers increased the smooth condition of small-caliber vascular scaffold and will be an important reference for the development of small-caliber vascular scaffold research...