| According to《Reprot on Cardiovascular Health and Diseases Burden in China: an Updated Summary of 2020》released in June 2021,the number of patients with cardiovascular diseases is about 330 million and the cardiovascular disease has become the primary threat to the population health in China.Vascular lesion is one of the significant symptoms of cardiovascular diseases.The replacement of damaged vessels is an effective treatment for patients with severe cardiovascular diseases.Currently,the large diameter artificial blood vessel(Inner Diameter>6 mm)based on non-degradable polymer materials has made significant progress in clinic.However,the small diameter artificial blood vessel(Inner Diameter≤6 mm)made of non-degradable materials hardly satisfy the clinical requirement due to easy thrombosis formation and low rate of long-term patency after implantation.Therefore,it is really vital to develop the small diameter artificial blood vessel for clinical application.In contact with blood,rapid short-term thrombosis and low long-term endothelialization are the key reasons hindering the application of small diameter artificial blood vessel.Adding external drugs or growth factors may not be the optimal strategy due to burst release of loaded drugs or growth factors.Therefore,physical and chemical modifications of the small diameter artificial blood vessel,aiming at dual roles of anticoagulation and promoting endothelialization may be effective solutions to solve the poor long-term patency.A series of small diameter artificial blood vessels with anticoagulation and promoting endothelialization have been constructed.The main contents of this study consist of the three parts:(1)A small diameter artificial blood vessel was fabricated with continuous anticoagulation and oriented fibrous intima.The small diameter artificial blood vessel was composed of heparinized silk fibroin and polycaprolactone.A two-step cross electrospinning technique was used to fabricate the small diameter artificial blood vessel which was endowed with oriented fibrous intima and porous fibrous adventitia.The oriented fibrous inner layer enabled to regulate the paralleled alignment and elongation of endothelial cells and promote endothelialization,while the porous outer layer was conducive to cell adhesion.Heparinized silk fibroin can inhibit the rapid formation of thrombus after in vivo transplantation.In vivo experiment of rabbit carotid artery transplantation verified the ability of anticoagulation and endothelialization of the small diameter artificial blood vessel.(2)To improve the ability of the small diameter artificial blood vessel in regulation of vascular endothelial cells and smooth muscle cells on the basis of the first work,a small diameter artificial blood vessel was constructed with catalytically endogenous nitric oxide generation and oriented fibrous intimal.A modified coating that could catalyze the endogenous generation of nitric oxide was constructed on the oriented fibrous intima by two-step cross electrospinning technique and coating modification.In vitro cell and anticoagulation experiments exhibited that the artificial blood vessel had the ability of anticoagulation,promoting endothelial cells proliferation and inhibiting vascular smooth muscle cells proliferation.The experiment of rat abdominal aorta replacement proved that the small diameter artificial blood vessel had the ability of anticoagulation,promoting endothelialization,and can realize the regeneration of vascular tissues.(3)In order to make up for the deficiency of two-step cross electrospinning technique and realize the biomimetic construction of the grooved structure on the natural vascular intima,a small diameter artificial blood vessel with natural vascular morphology was prepared based on freeze-casting technique.The previous study showed the natural vascular intima is a grooved structure.The protein materials were used to construct the small diameter artificial blood vessel by freeze-casting technique.In vitro cell and anticoagulation experiments showed that the artificial blood vessel by freeze-casting technique had the ability of anticoagulation and promoting endothelialization.The results of numerical simulation showed that the biomimetic intima was able to regulate hemodynamics and inhibit platelet activation.The experiment of rabbit carotid artery replacement confirmed that the small diameter artificial blood vessel with the biomimetic vascular intima could resist blood coagulation,promote endothelialization and complete the regeneration of vascular tissues.In conclusion,to overcome rapid thrombosis and poor endothelialization,three kinds of small diameter artificial blood vessels with anticoagulantion and promoting endothelialization were fabricated based on a series of methods,such as electrospinning technique,chemical modification,coating modification and freeze-casting technique.This study explores and develops small diameter artificial blood vessels from two aspects of materials system and construction strategy. |
