Shortening the manufacturing process of degradable magnesium alloy minitube for vascular stents by introducing cyclic extrusion compression

Due to its excellent biocompatibility and biodegradability,Mg and its alloys are considered to be promising materials for manufacturing of vascular sent.However,the manufacture of high-precision and high-performance Mg alloys minitubes is still a worldwide problem with a long manufacturing processing caused by the poor workability of Mg alloys.To solve this problem,the cyclic extrusion compression(CEC)was used to pretreat the billet by improving the workability of Mg alloys,finally shortening the manufacturing process.After CEC treatment,the size of grains and second phase particles of Mg alloys were dramatically refined to 3.2μm and 0.3μm,respectively.Only after three passes of cold drawing,the wall thickness of minitube was reduced from 0.200 mm to 0.135 mm and a length was more than 1000 mm.The error of wall thickness was measured to be less than 0.01 mm,implying a high dimensional accuracy.The yield strength(YS),ultimate tensile strength(UTS)and elongation of finished minitube were 220±10 MPa,290±10 MPa and 22.0±0.5%,respectively.In addition,annealing can improve mechanical property and corrosion resistance of minitubes by improving the homogeneity of the microstructure and enhancing the density of basal texture.

The deteriorated degradation resistance of Mg alloy microtubes for vascular stent under the coupling effect of radial compressive stress and dynamic medium

The degradation of Mg alloys relates to the service performance of Mg alloy biodegradable implants.In order to investigate the degradation behavior of Mg alloys as vascular stent materials in the near service environment,the hot-extruded fine-grained Mg-Zn-Y-Nd alloy microtubes,which are employed to manufacture vascular stents,were tested under radial compressive stress in the dynamic Hanks'Balanced Salt Solution(HBSS).The results revealed that the high flow rate accelerates the degradation of Mg alloy microtubes and its degradation is sensitive to radial compressive stress.These results contribute to understanding the service performance of Mg alloys as vascular stent materials.

The misalignment between degradation rate and mechanical integrity of Mg-Zn-Y-Nd alloy during the degradation evaluation in modified Hanks’solutions

The degradation behavior of biodegradable Mg alloys has become a research hotspot in the fields about biodegradable metallic materials.While the most of the related publications mainly focused on the degradation rate of Mg-based materials,but rare to care about the changes of their mechanical properties during the immersion period,which can significantly affect their service performance.The link between residual strength and Mg degradation is not appreciated enough.In this work,a series media were constructed based on Hanks’solution,the effects of inorganic ions on the degradation rate and mechanical integrity of Mg-Zn-Y-Nd alloy were investigated.The results indicated that the degradation behavior of Mg alloy was mainly controlled by degradation products and there is no direct correspondence between the degradation rate change and mechanical integrity of Mg alloy.The relevant findings are beneficial for selecting the monitoring index in Mg corrosion tests and evaluating the service reliability of Mg alloys for biomedical applications.

Effect of rare earth and Mn elements on the corrosion behavior of extruded AZ61 system in 3.5 wt%NaCl solution and salt spray test

In this study,multiple addition of rare earth(RE)and manganese(Mn)to AZ61 was conducted aiming to find out the influence to corrosion resistance.AZ61 containing different amounts of RE and Mn was investigated by electrochemical measurement in condition of 3.5 wt%NaCl solution at 25°C.Gravimetric measurement was conducted in 5 wt%salt spray at 35°C and 3.5 wt%NaCl solution at 25°C.Samples were characterized by SEM,EDS,OM and XRD.The result shows that with RE addition Al8Mn5 in AZ61 changed into Al10RE2Mn7.The quantity ofβphase is reduced significantly.The multiple addition of RE and Mn improved the corrosion resistance of AZ61.When the ratio of Mn and RE is 0.3,alloy has the best property of corrosion resistance.In addition,the composite addition removed the impurity elements in AZ61 especially Fe.

Corrosion fatigue of the extruded Mg-Zn-Y-Nd alloy in simulated body fluid

Magnesium alloys were considered to be used as biodegradable implants due to their biocompatibility,biodegradability and nontoxicity.However,under the simultaneous action of corrosive environment and mechanical loading in human body,magnesium alloys are easy to be affected by corrosion fatigue and stress corrosion cracking.In this work,the fatigue behavior of the extruded Mg-Zn-Y-Nd alloy used for vascular stents was studied both in air and in simulated body fluid(SBF).It was revealed that the fatigue limit of as-extruded Mg-Zn-Y-Nd alloy in air is about 65 MPa at 10^7 cycles,while there is no limit in SBF and shows a linear relationship between the fatigue life and stress amplitudes.The fatigue crack source in air was formed by the inclusions and defects.However,the stress corrosion and hydrogen embrittlement are the main reasons for the formation of the fatigue initial crack source in SBF.

Microstructure and texture evolution of fine-grained Mg-Zn-Y-Nd alloy micro-tubes for biodegradable vascular stents processed by hot extrusion and rapid cooling

Magnesium alloys have narrow available slip result from close-packed hexagonal structure that limit their processing properties.In the recent work,the Mg-2Zn-0.46Y-0.5Nd,as materials for degradable stents,was applied to produce as-extruded micro-tube with an outer diameter of 3.0mm and a wall thickness of 0.35mm by hot extrusion with an extrusion ratio of 105:1 at 653K and rapid cooling.The fine microstructure of the dynamic recrystallization of as-extruded micro-tube could be preserved by rapid cooling such as water-cooled,resulting in more excellent mechanical properties relative to air-cooled micro-tube.The addition of rare earth elements Y and Nd results in continuous dynamic recrystallization dominated the dynamic recrystallization mechanism.During the hot extrusion process,the activation of the non-basal slip system,especially the pyramidal(c+a)slip,could significantly weaken the texture strength,and the as-extruded micro-tube exhibits weak"RE"texture components(011^(-)1)||ED and(1^(-)21^(-)1)||ED.Hence,the magnesium alloy micro-tube prepared by the rapid cooling has fine microstructure and weak texture,which is favorable for further process and governance.

Decreased serum HMGB1 associated with M2 macrophagepolarization and patients with calcific aortic valve disease

Except for the standard aortic valve replacement,no effective medical treatment is available to prevent or delay calcific aortic valve disease(CAVD)progression.Recently,macrophages and high-mobility group box 1(HMGB1)are the most intriguing candidates in various inflammatory disorders.However,the association between serum HMGB1,CAVD,and macrophage polarization remains unclear.Therefore,we examined whether the level of serum HMGB1 is clinically associated with aortic valve calcification and whether HMGB1 treatment can promote macrophage differentiation toward M1 or M2 phenotype.This experimental study included 19 CAVD patients and 20 healthy controls whose serum HMGB1 levels were examined by ELISA assay.THP-1 macrophage polarization system was established to test the polarization capability of HMGB1 treatment.The results showed that serum levels of HMGB1 were significantly reduced in patients with CAVD.HMGB1 treatment promoted M2 macrophage polarization but not M1 phenotype with increased IL-10 expression and reduced inducible nitric oxide synthase(iNOS)expression.Our findings suggest that serum HMGB1 is negatively associated with the development of aortic valve calcification,and HMGB1 treatment may facilitate M2 macrophage polarization for reducing aortic valve calcification.

A two-step superplastic forging forming of semi-continuously cast AZ70 magnesium alloy

A two-step technology combined forging with superplastic forming has been developed to enhance the forgeability of semi-continuously cast AZ70 magnesium alloy and realize the application of the as-cast magnesium alloy in large deformation bullet shell.In the first step,fine-grained microstructure preforms that are suitable for superplastic forming were obtained by reasonably designing the size of the initial blanks with the specific height-to-diameter ratio,upsetting the blanks and subsequent annealing.In the second step,the heat treated preforms were forged into the end products at the superplastic conditions.The end products exhibit high quality surface and satisfied microstructure.Consequently,this forming technology that not only avoids complicating the material preparation but also utilizes higher strain rate superplastic provides a near net-shaped novel method on magnesium forging forming technology using as-cast billet.

In vitro corrosion properties of HTHEed Mg-Zn-Y-Nd alloy microtubes for stent applications:Influence of second phase particles and crystal orientation

Magnesium(Mg)alloys are promising materials for cardiovascular stent applications due to their good biocompatibility and biodegradability.However,in vitro and in vivo corrosion tests reveal that Mg alloy stents suffer from a rapid corrosion rate and severe localized corrosion,which is limiting their widespread application.To solve the problem of uneven degradation of stents,a HTHE(long-time and high-temperature heat treatment,large-reduction-ratio hot extrusion)process is used to manufacture Mg-Zn-Y-Nd alloy microtubes in this study.The heat treatment is to dissolve alloying elements and reduce the size of SPPs,and the hot extrusion is to acquire fine-grained and strongly textured microtubes.The microstructural characterization shows that coarse second phases in as-cast alloy are refined and uniformly distributed in matrix of microtubes.After hot extrusion,microtubes show strong texture with basal plain oriented parallel to the longitudinal section(LS).The corrosion testing indicates that severe localized corrosion occurs on the cross section(CS)while localized corrosion is alleviated on the LS.Based on the different corrosion properties of the LS and CS,HTHEed microtubes are promising for solving the problems of rapid corrosion rate and severe localized corrosion of Mg alloy stents.

Preparation of functional coating on magnesium alloy with hydrophilic polymers and bioactive peptides for improved corrosion resistance and biocompatibility

Biodegradable magnesium alloy stents(MAS)have great potential in the treatment of cardiovascular diseases.However,too fast degradation and the poor biocompatibility are still two key problems for the clinical utility of MAS.In the present work,a functional coating composed of hydrophilic polymers and bioactive peptides was constructed on magnesium alloy to improve its corrosion resistance and biocompatibility in vitro and in vivo.Mg-Zn-Y-Nd(ZE21B)alloy modified with the functional coating exhibited moderate surface hydrophilicity and enhanced corrosion resistance.The favourable hemocompatibility of ZE21B alloy with the functional coating was confirmed by the in vitro blood experiments.Moreover,the modified ZE21B alloy could selectively promote the adhesion,proliferation,and migration of endothelial cells(ECs),but suppress these behaviors of smooth muscle cells(SMCs).Furthermore,the modified ZE21B alloy wires could alleviate intimal hyperplasia,enhance corrosion resistance and re-endothelialization in vivo transplantation experiment.These results collectively demonstrated that the functional coating improved the corrosion resistance and biocompatibility of ZE21B alloy.This functional coating provides new insight into the design and development of novel biodegradable stents for biomedical engineering.

Degradation of Mg-Zn-Y-Nd alloy intestinal stent and its effect on the growth of intestinal endothelial tissue in rabbit model

Biodegradable magnesium alloys have excellent properties with respect to biodegradability, biocompatibility, and biomechanics, which may indicate a possibility of its application in intestinal stents. Investigation of Mg-Zn-Y-Nd alloy’s application in intestinal stents has been performed. This study aims to investigate the degradation behavior of Mg-Zn-Y-Nd alloy intestinal stents coated with poly(L-lactide)/paclitaxel in the intestinal environment and its biocompatibility with intestinal tissue. In this paper, Mg-Zn-Y-Nd alloy’s corrosion properties were evaluated by the immersion test in human feces, SEM and XRD, and animal tests. In vitro results showed that when the Mg-Zn-Y-Nd alloy was immersed in human feces for two weeks, its corrosion resistance could be improved by micro arc oxidation(MAO) and poly-l-lactide(PLLA) dual coating. Additionally, this result was also confirmed in vivo experiments by rabbit model. And animal tests also demonstrated that the Mg-Zn-Y-Nd alloy with MAO/PLLA/paclitaxel dual coating drug-eluting stents could inhibit the proliferation of local intestinal tissue around the stents. However, in vivo studies illustrated that the intestinal stents gradually degraded in rabbit model within 12 days.Considering the degradation rate of the stent was faster than expected in rabbits, the support performance of the scaffold requires further improvement.

Mg alloy cardio-/cerebrovascular scaffolds: Developments and prospects

Vascular scaffolds are one of the important application fields of biodegradable Mg alloys, and related research has been carried out for more than 20 years. In recent years, the application expansion of Mg alloy vascular scaffolds has brought new challenges to the research of related fields. This review focuses on the relevant advances in the field of Mg alloys for both cardio-/cerebrovascular scaffolds. The frequently investigated alloy series for vascular scaffolds were reviewed. The bottleneck of processing of Mg alloy minitubes was elucidated.The idea of functionalized surface modification was also pointed out in this review, and the authors put forward guidelines based on research experience in terms of scaffold structural design and degradation behavior evaluation. Finally, suggestions for further research directions of Mg alloy vascular scaffolds were provided.

Initial micro-galvanic corrosion behavior between Mg_(2)Ca and α-Mg via quasi-in situ SEM approach and first-principles calculation

The initial micro-galvanic corrosion behavior of Mg-30wt%Ca alloy only containing Mg_(2)Ca andα-Mg was studied by immersion testing in a 0.9%Na Cl solution at 37°C.The quasi-in situ SEM and TEM results show that Mg_(2)Ca corroded easier thanα-Mg,indicating that Mg_(2)Ca acted as an anode.The work function(Φ)for Mg_(2)Ca calculated by first-principles is significantly lower compared to that forα-Mg.The Volta potential measured by a scanning Kelvin probe force microscope reveals that the Mg_(2)Ca had a relatively low Volta potential(ψ)value.The lowerΦandψvalues for Mg_(2)Ca indicate a lower electrochemical nobility,which is consistent with the experimental phenomenon.

A promoting nitric oxide-releasing coating containing copper ion on ZE21B alloy for potential vascular stent application

Magnesium-based biodegradable metals as cardiovascular stents have shown a lot of excellent performance, which have been used to treat coronary artery diseases. However, the excessive degradation rate, imperfect biocompatibility and delayed re-endothelialization still lead to a considerable challenge for its application. In this work, to overcome these shortcomings, a compound of catalyzing nitric oxide(NO) generation containing copper ions(Cu^(2+)) and hyaluronic acid(HA), an important component of the extracellular matrix, were covalently immobilized on a hydrofluoric acid(HF)-pretreated ZE21B alloy via amination layer for improving its corrosion resistance and endothelialization. Specifically,the Cu^(2+) chelated firmly with a cyclen 1,4,7,10-tetraazacyclododecane-N’, N’’, N’’’, N-tetraacetic acid(DOTA) could form a stability of hybrid coating, avoiding the explosion of Cu^(2+). The chelated Cu^(2+) enabled the catalytic generation of NO and promoted the adhesion and proliferation of endothelial cells(ECs) in vascular micro-environment. In this case, the synergistic effect of NO-generation and endothelial glycocalyx molecules of HA lead to efficient ECs promotion and smooth muscle cells(SMCs) inhibition. Meanwhile, the blood compatibility also had achieved a marked improvement. Moreover, the standard electrochemical measurements indicated that the functionalized ZE21B alloy had better anti-corrosion ability. In a conclusion, the dual-functional coating displays a great potential in the field of biodegradable magnesium-based implantable cardiovascular stents.

Zn content mediated fibrinogen adsorption on biodegradable Mg-Zn alloys surfaces

The protein adsorption has an immense influence on the biocompatibility of biodegradable Mg alloy.In this work,the effect of Zn content on the fibrinogen(Fg)adsorption behavior in Mg-Zn binary alloy was systematically investigated.Experimental results showed that the Fg adsorption amount increased at first and then decreased with the increase of Zn content.The adsorption mechanism was investigated by molecular dynamic and density functional theory simulations.The simulations results showed that Zn with low content existed in the inner layer of Mg alloys due to the lower system energy,which promoted Fg adsorption and the promotion effect was more obvious with the increase of Zn content.When Zn content increased to a higher concentration,parts of Zn atoms started to precipitate in the surface,and the Fg-surface interaction energy started to increase.Moreover,the Zn sites favored the formation of ordered water molecules layers,which inhibit the stable adsorptions of Fg.The inhibition effects of Fg adsorption was enhanced with the Zn content increase.In short,the simulation results explain the experimental phenomena and reveal the microscopic mechanism.This study would provide a significant guidance on the design of biodegradable Mg-Zn alloys.

多重交联水凝胶体系的抗剪切性能评价研究

凝胶调驱体系注入过程中的强剪切降解作用严重阻碍了施工应用效果,改善凝胶调驱体系的抗剪切性能,实现高效的深部调驱十分重要。通过对比疏水缔合聚合物(DHAP)与部分水解聚丙烯酰胺为主剂(HPAM)的多重交联水凝胶体系,开展抗剪切性、成胶性能、老化稳定性、封堵能力和调驱效果等内容研究。结果表明:疏水缔合聚合物在经历注入速度为175 mL/min的炮眼剪切后,黏度损失率仅4%,交联成胶后依然具备15 Pa·s的高强度,在多孔介质中的封堵率能够达到91%;在并联岩心驱替实验中,能够有效调驱,扩大对低渗岩心的波及效率,比HPAM为主剂的体系提高10%的原油采收率。通过适当降低共价交联密度,构筑的适度共价交联+非共价交联的水凝胶体系,能够在多孔介质中建立起较好的调驱作用能力。

High Temperature Creep behaviour of a Si_3N_4 Whisker Reinforced Al-Fe-V-Si Composite

The creep behaviour of β-Si3N4 whisker reinforced Al-8.5Fe-1.3V-1.7Si composite has been investigated at the temperature 773 and 823 K. The results are characterized by high stress exponent and high apparent creep activation energy The creep data can be interpreted based on the incorporation of a threshold Stress and a load transfer coefficient into the power-law creep equation. A good correlation between the normalized creep rate and normalized effective stress is available which demonstrates that the creep behaviour of both the alloy and the composite is controlled by the matrix lattice self-diffusion in AI. EXamination on microstructure shows that edge dislocations exist at the interfaces between two adjacent whiskers and the intedeces emit edge dislocations in parallel paired-columns.

Study on medication regularity of traditional Chinese medicine cases in treatment of neoplastic fever based on data mining

Objective:To analyze the medication regularity of traditional Chinese medicine cases in treatment of neoplastic fever in order to guide clinical medication.Methods:The database of China National Knowledge Infrastructure,Vip database and WanFang medical network were searched.The cases involving traditional Chinese medicine prescription in the treatment of neoplastic fever were screened.After extracting the prescriptions and Chinese medicines,make statistics according to frequency analysis,cluster analysis and association analysis.Results:79 literatures were included which involving 123 decoctions.221 traditionalChinese medicines were included in the statistics,the most frequently used traditional Chinese medicines were Gancao,Chaihu,Huangqi and Shengdihuang.The proportion of heat-clearing drugs in Chinese medicines was the largest(23.98%).The most common property of the Chinese medicines is cold property,accounting for 51.13%.The higher frequencies of flavors of the Chinese medicines are bitter,sweet and acrid,the sum of which is 84.66%.The most common meridian of Chinese medicines is liver meridian,accounting for 19.82%.The cluster analysis and association analysis of high frequency Chinese medicines showed that high frequency Chinese medicines could form three clustering formulas,and could get 18 pairs of high frequency drug combinations.Conclusion:Traditional Chinese medicines for heat-clearing,deficiencytonifying,phlegm-resolving,blood stasis-dispeling are mostly used to the treatment of neoplastic fever.The results of cluster analysis and association analysis of high frequency traditional Chinese medicines can provide certain reference and guidance for clinical medication.

Fracturing-flooding technology for low permeability reservoirs:A review

The development of low-permeability oil and gas resources presents a significant challenge to traditional development methods.To address the problem of“no injection and no production”in low-permeability reservoirs,a novel fracture-injection-production integration technology named fracturing-flooding has been proposed by oilfield sites.This technology combines the advantages of conventional fracturing,water flooding,and chemical flooding,resulting in improved reservoir physical properties,increased injection,replenished energy,and increased oil displacement efficiency.The technology is especially suitable for low-permeability reservoirs that suffer from lack of energy,and strong heterogeneity.Fracturing-flooding technology has shown significant results and broad development prospects in some oilfields in China.This paper analyzes the development status of fracturing-flooding technology from its development history,technical mechanism,technical characteristics,process flow,types of fracturing and oil displacement fluids,and field applications.Physical and numerical simulations of fracturingflooding technology are also summarized.The results suggest that fracturing-flooding technology is more effective than conventional fracturing,water flooding,and chemical flooding in stimulating lowpermeability tight reservoirs and improving oil recovery.Moreover,it has a high input-output ratio and can be utilized for future reservoir stimulation and transformation.