| Coronary heart disease caused by cardiovascular stenosis is threatening humanhealth now. The major therapeutic strategies include drug therapy, coronary arterybypass grafting(CABG) and interventional treatment. Drug therapy is a conservativetreatment with slow effects. In addition, patients will easily rely on drug after chronicdrug intake. The wound of CABG heals slowly, which will increase patients’ pain.Percutaneous transluminal coronary angioplasty(PTCA) can minimize the trauma.However, the in-stent restenosis unexpectedly develops after6-8months of PTCA. Howto reduce and avoid in-stent restenosis (ISR) has become a primary issue. Therefore, thechoice of stent materials is particularly important. Now stent materials mainly includenon-degradable and degradable materials. The non-degradable stent materials includecommon stainless steel, cobalt, nickel titanium alloys. However, these metal materialsdo not degrade. and they will retain in the body permanently, which will increase therisk of restenosis.In order to overcome the problem, biodegradable stents materials have been paidmore attention by many researchers. Common biodegradable stents materials mainlyinclude biodegradable polymer materials, pure iron and magnesium alloys. Althoughpolymer materials have many advantages as stent materials, the same radial force withblood vessels is not guaranteed in the stent implantation, which restricts its retractionrebound. In addition, the balloon can not expand fully for this type of stent implantation.It needs heat, which brings the unpredictable damage to patients. Because the density ofpolymer materials is small and they can not use X-ray imaging technique, the stentimplantation is difficult to position. As for iron materials, they can overcome theseproblems. However the degradation rate is slow in the body, the vascular repair and thedegradation of stent can not achieve the synchronization. Therefore, the development ofnew biodegradable stent materials is imperative. Because magnesium alloys are cheapand degradable, with good mechanical compatibility and biocompatibility, magnesiumalloys have become research hotspot for stent materials.Based on the above analysis, the researchers have ruled out the high allergenicity ofnickel and neurotoxicity of aluminum element, and chosen Y, Nd and Zr as alloyingelements with a variety of biological functions. This paper changed the ratio of alloyelements and prepared a series of magnesium alloys. This study also investigated their degradation behaviors and biocompatibility, discussed the degradation mechanism andfound the new types of WE magnesium alloys for stent materials. In order to study thebiological safety of materials, we choosed zebrafish to test which has87%of genesimilarity with human body. This means that the toxicity tests on zebrafish also apply tothe human body in most cases. Therefore, the impact of magnesium alloys on thesurvival of zebrafish embryos was used to determine the safety of the materials.Magnesium oxide forms easily on the surface of magnesium and magnesium alloys. Themagnesium oxide of large size is not toxic to human body. While whether it is toxicwhen the size of magnesium oxide is small remains unknown. So we studied thetoxicity of nano magnesium oxide to test the existing toxic substances. The maincontent of the paper and the results are as follows:①Y and Nd as alloying elements could effectively refine the grain size, but therefinement was very limited. When Y content reached5.0%, Nd content reached2.6%,the grain refinement basically no longer had the change. Nd as an alloy element, on theone hand, improved the strength of the alloy, while on the other hand reduced the alloyductility. Strength and yield strength also increased with Y content. Y improved theductility. When Y content was2.5%, the alloy’s plasticity was satisfied. As Y increased,the plastic properties of the alloy reduced. Along with the extension of corrosion time,corrosion solution was alkaline during static and dynamic corrosion, the sample losswould increase gradually. The mass loss of magnesium alloy was lower. The corrosionpotential of magnesium alloy was more positive than pure magnesium. This showed thatthese magnesium alloys had better corrosion resistance compared to pure magnesium.②Magnesium and magnesium alloys reduced the hatching rate of zebrafish. But theeffects on the death rate of zebrafish embryos, sediment rate of melanin, tail extendingrate, eyespot development rate and zebrafish length were not significant, indicating thatmagnesium alloys had no obvious toxicity for zebrafish development and growth. Whennano magnesium oxide was less than concentration of160mg/L, zebrafish did not haveacute toxicity. The spontaneous movement of20s at24h reduced gradually, but theexperimental groups had no significant difference campared to the control group. Andthe effects on the zebrafish length,24hpf eyespot development rate, malformation rateand48hpf sediment rate of melanin were not significant. In addition, low concentration(below500μg/ml) of nano magnesium oxide suspension showed no cytotoxicity byMTT assay. However, once the concentration of nano magnesium oxide was higherthan500μg/ml, the relative growth rate (RGR) was lower than the control. The staining analysis results showed no significant difference for cells morphology between thegroups with or without nano magnesium oxide. The nano magnesium oxidesignificantly enhanced the nitric oxide (NO) release and total antioxidant capacity(T-AOC) content of the HUVECs. The testing results indicated that low concentrationof nano magnesium oxide exhibited non-cytotoxicity.③With the increase of rare earth elements, platelet adhesion increased firstly, anddecreased, then had an increasing trend. Fibrinogen adsorption decreased with theincrease of rare earth elements. The coagulation function improved. The magnesiumalloys greatly reduced the hemolysis rates, but they were still higher than the safetyvalue of5%, which required further surface modification to improve their hemolyticproperties. When rare earth elements excessively increased, which in turn affectedvascular endothelial cells proliferation, at the same time the inhibition of vascularsmooth muscle cells increased. The magnesium alloys increased NO release, whilelactate dehydogenase (LDH) release was not significantly affected. Magnesium alloysalso promoted the adhesion of endothelial cells. Along with the increase of adhesiontime, cell adhesion numbers increased gradually. The25%extracts of all materialspromoted cell migration, while100%extracts were not conducive to cell migration.④Based on the above analysis, Mg-5.0Y-2.6Nd-0.8Zr and Mg-6.5Y-2.5Nd-0.8Zrhave better comprehensive performance compared to Mg-2.5Y-1.0Nd-0.8Zr andMg-7.5Y-4.2Nd-0.8Zr, and can be used as candidate materials for medical stents.Although the toxicity studies of nano magnesium oxide and magnesium alloys onzebrafish and cells show that magnesium alloys are safe, but these still can notcompletely define these materials’ toxicity. The evaluation standard to define the toxiclevel of materials is deficient. The influence of the materials on the zebrafish survival isa macro toxicological observation. These studies provide basis and reference for ournext job. They also provide more reference for the comprehensive evaluation of thesafety of magnesium alloys. |
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