Design And Functionalization Of ZE21B Magnesium Alloy By Schiff Base-loaded Coatings Vascular Stents

With the improvement of people’s living standards,cardiovascular and cerebrovascular diseases have become the number one killer with the highest cause of death.Interventional therapy has become one of the most important treatment methods.Therefore,the demand for cardiovascular stents has also increased year by year.Magnesium alloy has become one of the most potential vascular stent implant materials due to its excellent biocompatibility,good biodegradability and adaptive biomechanical properties,and it has become a research hotspot of vascular stent materials.Nevertheless,duo to the relative active chemical properties of magnesium,its degradation rate is too fast in the physiological environment,and its endothelialization is relatively slow during the service life,which hinders its large-scale clinical application.In response to the above two major problems,this thesis employs ZE21B magnesium alloy as the research object,and screens out biocompatible magnesium alloy degradation inhibitors from natural products,animal extracts,marine biological active ingredients,and commercial drugs guided by complex theory.Three highly effective Schiff bases(i.e.PCTyr Schiff base,PCPhe Schiff base and PCCys Schiff base)were synthesized from condensation paeonol with amino acids(tyrosine,phenylalanine and cysteine).The sol-gel coating loaded with Schiff base degradation inhibitor was designed to control the degradation performance and improve the biocompatibility of ZE21B.The degradation inhibition behaviors of three Schiff bases in physiological saline were studied by static weight loss,electrochemical test,ion dissolution,Fourier transform infrared spectrum(FT-IR),X-ray photoelectron spectroscopy(XPS)and other methods.The results showed that the added amount of the Schiff base has a significant impact on degradation inhibition efficiency.PCTyr Schiff base,PCPhe Schiff base and PCCys Schiff base showed the highest corrosion inhibition efficiency of 79.4%,90.2%and 91.6%at 3 m M,10m M,and 10m M respectively.In this thesis,based on the first principles and Gauss software,the B3LYP method in density Functional Theory(DFT)was used to calculate the bond length,bond Angle,dihedral Angle,HOMO,LUMO orbital energy,and other parameters of the corrosion inhibitor,to reveal the action principle of this kind of Schiff base corrosion inhibitor on the electronic and molecular level.The sol-gel coating loaded with Schiff base degradation inhibitor was innovatively designed.Combining with EDS and FT-IR spectroscopy,the composition and formation mechanism of the coating was revealed.The Schiff base was loaded in the sol-gel in the form of doping,and these two could coexist harmoniously without chemical reaction,the main elements of the coating are C,O and Si;the thickness of the Schiff base coating is 4～5μm,which satisfies the required coating thickness of magnesium alloy vascular stents.The influence of loading Schiff base degradation inhibitor on the degradation resistance of the coating has been studied through in vitro weight loss and electrochemical tests.Loading the Schiff base significantly improves the degradation resistance of the coating,especially the sol-gel loaded with PCCys schiff base,its coating degradation rate(0.03 mg/cm~2 h)is the lowest;the test results of atomic force microscopy(AFM),water contact angle,and bonding strength show that loading Schiff base degradation inhibitors improves the surface roughness of the coating and increaes the wettablity of the coating.The self-healing function of Schiff base coating is studied by pre-scratched immersion tests.The results show that the self-healing behavior can be completed by immersing in simulated body fluid(SBF)at 37~oC for 7 days.At the same time,the coating is proposed a self-healing mechanism combining its slow release and Schiff base degradation inhibition.Finally,the biocompatibility of sol-gel coating loaded with Schiff base degradation inhibitor was evaluated by using cytocompatibility and blood compatibility.The blood compatibility shows that the Schiff base coating reduces the adhesion and activation of platelets,indicating that the Schiff base coating on ZE21B has the biological functions of anticoagulation and low hemolysis;the cytocompatibility results show that the Schiff base coating has no cytotoxicity.Especially the combination of PCCys schiff base and the coating promotes the rapid endothelialization,and its scratch healing width is as high as 455.95μm within 36 hours,which is mainly due to the good resistance to oxidative damage of Schiff base.At the same time,loading Schiff base degradation inhibitors enhances the competitive growth of endothelial cells,inhibits the excessive proliferation of smooth muscle,and provides the possibility to replace traditional drug-loaded(rapamycin,paclitaxel,sirolimus,etc.)coatings.Comprehensive analysis of the experimental results of the degradability and biocompatibility of the Schiff base coating on the ZE21B magnesium alloy shows that the sol-gel coating loaded with PCCys Schiff base performs best.This thesis discovered the Schiff base degradation inhibitors that significantly reduce the degradation rate of ZE21B magnesium alloy via the comprehensive screening.The combination of degradation inhibitor with the sol-gel coating further improves the degradation inhibition performance of the coating.The Schiff base-loaded coating has multiple functions such as self-healing,rapid endothelialization,and inhibition of hyperplasia,providing a new way for the design of magnesium alloy multi-functional coatings for vascular stents.