Research On The Effect Of Polylactic Acid-based Bioabsorbable Vascular Stent Materials On Vascular Endothelialization

Statistics of China Cardiovascular Disease report in 2017 showed that the number of people suffering from cardiovascular diseases in China has reached 290 million.Since the first bare metal coronary stent implantation in 1986,percutaneous coronary intervention has been developed and improved for a long time.It has become the most widely used cardiovascular disease diagnosis and treatment technology with its advantages of high efficiency and minimally invasive.However,it is prone to lead to various adverse events,including restenosis in stents,neointimal hyperplasia and stent thrombosis.With the development of this field,bioresorbable scaffold has become a promising product.After the mechanical support of blood vessels,it was finally degraded into harmless molecules without remaining in human body.At the same time,BRS showed a low incidence of ISR or late ST,which was considered to be the fourth revolution of PCI technology.The BRS mainly includes polymer degradable stents and metal absorbable stents.At present,polylactic acid is widely used in polymer degradable stents.Polylactic acid and its copolymers are biodegradable materials.Their degradation products are water and carbon dioxide,which have good absorbability and biocompatibility.Although polylactic acid bioabsorbable stents show good propects,recent long-term follow-up data from randomized trials and observational studies show that stents still have worrisome signs of late thrombus and a higher risk of restenosis,which reduce the survival rate and the quality of life of the patients.Previous studies have shown that the injury of endodermis is the main cause of restenosis.Therefore,promoting the process of endothelialization of the implanted site,reducing the restenosis rate,avoiding the formation of thrombus and improving the success rate of PCI,are the main problems to be solved urgently.At present,the study of bioabsorbable scaffolds mainly focuses on biocompatibility in vivo and in vitro.Some study of vascular endothelialization after implantation merely focuses on the drug or growth factor coated on the stent.However,the effect of polylactic acid coating and the main material on vascularendothelialization period after vascular injury is unknown.Therefore,this study investigates the effects of bioabsorbable scaffolds and coating materials on endothelialization.There is a qualitative and quantitative study on the main material and coating material of scaffold,and the effect on the human umbilical vein.The effects of cell morphology,cell growth activity,cell migration,vascular formation and the expression of related molecules such as VEGF ? NO were studied.It can provide theoretical and experimental basis for the development of new stent materials and explore the mechanism of vascular stent endothelialization.In the first chapter,it is confirmed by NMR that the coatings and the main materials are PDLLA and PLLA.The concentration of lactic acid in the degradation process of scaffold was determined by HPLE-MS,which provide data support to the following chapters.In the second chapter,the cell composite scaffold was cocultured in vitro.The scaffold was a specially designed scaffold without drugs.The purpose of this study was to observe the growth state of HUVEC cells on the surface of scaffold.Hoechst staining and scanning electron microscopy showed that the cells could adhere and proliferate well on the scaffold.It was also found that HUVEC cells could adhere and proliferate on the polylactic acid scaffold without any intervention factors,which provided some data support for the future research of polylactide scaffolds in vitro.In the third chapter,the proliferation,migration and formation of vascular of HUVEC cells which are closely related to the repair process after vascular injury were studied.The results showed that the PLLA group could promote cell proliferation at different time points,and it was better than PDLLA group.In HUVEC cell migration,the scaffold coating group and the main material group had no obvious effect compared with the control group.In HUVEC cell tube formation,such as PDLLA group(30 days)showed a significant inhibition on the formation of vascular.However,in the early stage of biodegradation,the vascularization function was promoted to some extent.It is speculated that the proper concentration of lactic acid may promote the endothelialization of HUVEC,mainly by affecting the proliferation of endothelial cells and the formation of vascular.Higher concentration of lactic acid inhibited its angiogenesis.In the fourth chapter,the expression of VEGF and e NOS in HUVEC cells were investigated.The results showed that the scaffold coating material could up-regulate the expression of e NOS and VEGF m RNAs,but the expression of VEGF protein and NO molecule was inhibited to some extent.These results suggest that the stent coating may inhibit the repair of vascular endothelium and delay the process of vascular endothelialization.In this paper,the effects of polylactic acid scaffolds on vascular endothelialization were revealed.The corresponding exploration was also carried out at the cellular and molecular levels.The conclusions provide some theoretical and data support for exploring new angles to promote vascular endothelialization.