The Study On The Small-diameter Biodegradable Artificial Blood Vessel Fabricated By Co-Electrospinning Of Gelatin-PLCL

Cardiovascular disease,with the highest mortality and morbidity,has caused over 1/3 death of patients all over the world.Vascular bypass surgery and interventional therapy are common treatment strategies in clinical.However,patients with severe stenosis or vascular disease are not suitable for stent implantation,also vascular bypass surgery is limited by autologous blood vessels.With the development of tissue engineering,artificial blood vessel has become a research focus.Now commercialized large-caliber artificial blood vessels have been used in clinical treatment with impressive long-term patency,but because of blockage or intimal hyperplasia,no ideal small-diameter artificial blood vessels(< 6 mm)can be applied to clinical treatment.Electrospinning can be used to prepare nanoscale fibers,and the artificial blood vessels prepared by electrospinning can simulate the structure and function of the extracellular matrix.Therefore it is widely used in the research of small diameter artificial blood vessels.While the compact fiber structure and the small pore size are not suitable for the migration of the cells to the stent,hence the regeneration and reconstruction of the replacement blood vessels are hindered.Poly(lactic acid)poly(caprolactone)(PLCL)possesses good mechanical properties,biocompatibility and biodegradability and gets more and more application in the field of biomaterials.However,the strong hydrophobicity and lack of modified group of PLCL,makes it adverse to r cell adhesion,proliferation,migration and differentiation.In this thesis,hybrid gelatin and PLCL are used as the material of electrospinning because of the high biological activity of gelatin and good mechanical properties of PLCL.The artificial blood vessel we prepared possesses low porosity,compact structure in the early stage,which are beneficial to conducive to the rapid endothelialization and reduce the incidence of early acute thrombosis.Later,with the dissolution of gelatin,the porosity increased gradually,which was favorable for cell growth and proliferation.In this paper,the main contents and results are as follows:1 Preparation and optimization of Gelatin-PLCL Co-electrospinning polymer fiber membraneMake up different proportions of Gelatin-PLCL hybrid electrospinning solution,prepare corresponding electrostatic spinning membrane with uniaxial electrospinning.The surface morphology of the samples was observed by SEM,and then calculate the diameter distribution of nanofibers.The results have showed that gelatin blending can obviously optimize the electrospinning of PLCL alone,which made the diameter of the spinning fiber more uniform,and the diameter decreases with the decrease of the proportion of gelatin within certain limits.Gelatin-PLCL(2:8)hybrid solution and 10% PLCL solution were used to prepare different kinds of Gelatin-PLCL co polymer fiber membranes by different electrospinning methods.We utilize SEM to observe the surface morphology and calculate the diameter distribution of nanofibers,static water contact angle test to detect the hydrophilic.The blood compatibility and cell compatibility was measured by hemolysis test,platelet adhesion test,MTS cytotoxicity test and cell adhesion test.The results showed that gelatin hybrid significantly enhanced the biological activity of PLCL materials for cell adhesion,proliferation,migration and so on.2 Preparation and properties study of Gelatin-PLCL Co small diameter artificial blood vesselAccording to the results of the properties study of Co polymer fiber membrane,the small diameter artificial blood vessel of experimental group was made by the combination of uniaxial and coaxial electrospinning,and the two nozzles were simultaneously spinning.The shell of coaxial was used Gelatin-PLCL(2:8)hybrid solution,the core layer was 10% PLCL solution,the uniaxial was also used Gelatin-PLCL(2:8)hybrid solution.The control group was treated with uniaxial electrospinning 10% PLCL and Gelatin-PLCL(2:8)hybrid solution.The mechanical properties and histocompatibility of the electrospinning artificial blood vessel were tested.The results showed that the mechanical properties and histocompatibility of PLCL electrospinning blood vessels could be improved by adding gelatin.3 Replacement experiment in a rat modelThe Gelatin-PLCL Co small diameter artificial blood vessel were implanted as new abdominal aorta interposition grafts in SD rats.At 1 week and 1 month after operation,the patency of the replacement segment was detected by vascular ultrasonography.And then remove the artificial blood vessel segment,the internal surface changes was observed by SEM,and the interaction of artificial blood vessels and the host was detected by histological analysis.The results showed that Gelatin-PLCL Co-electrospinning small diameter artificial blood vessel was favorable for the rapid endothelialization and the migration and growth of vascular cells in the early stage of transplantation.In summary,in order to prepare degradable small diameter artificial blood vessels which can achieve rapid endothelialization in early stage and later cell migration for vascular reconstruction,this paper explores the construction from material modification and structural design,which has laid a foundation of artificial blood vessels for the ideal clinical application.