Corrosion Behavior And Biocompatibility Of Degradable Metals Mg And Zn In Simulated Uterine Microenvironment

Contraception after delivery is vital for pregnant women,because the pregnancy in the breastfeeding period will have adverse effects on women and fetuses,especially for whom suffered from cesarean section.It is not only increase surgical the risk and difficulty of uterine rupture.but also bring unfavorable effects to the babies.So the reasonable postpartum contraception is important.Intrauterine device（IUD）,as a long-term,reversible and economical contraceptive measure,provides the necessary protection for postpartum contraception.However,the shedding problem of IUDs remains to solve.In addition,the most widely used IUD is the copper-containing intrauterine device（Cu-IUD）.but it can cause side effects such as excessive menstrual bleeding,pain,abnormal bleeding and inflammation.In this paper,we sought to apply biodegradable magnesium alloy to the development of IUD fixtures placed in time after delivery,to solve the problem of IUD dropout,and to explore the possiblity of zinc alloy in IUD materials.As a new generation of medical metal,magnesium alloy has many excellent properties.First of all,magnesium alloys have excellent mechanical properties and have strong specific strength and stiffness.Second,magnesium is an essential element of the human body and has a close relationship with the maintenance of life and the health of the body.Third,in the human body,magnesium is the second most important cation（Kalium is the first）and its content is second only to Kalium.Magnesium also has a variety of special physiological functions,it can activate a variety of enzymes in the body,as well as abnormal nerve excitation,maintain the stability of the nucleic acid structure,participate in the synthesis of protein in the body,muscle contraction and body temperature regulation.Magnesium also influences the "channel" of intracellular and extracellular movement of Kalium ion,Sodion,and calcium ion,and maintains the potential of biofilm potential.Importantly,the degradable properties of magnesium alloys can be absorbed by the body,avoiding the problem of secondary surgical removal after implantation.In 1968.Zipper,from Chile,found the copper and zinc and other metal salts have obvious anti-fertility effects.In the past several years,the copper-loaded IUD has been widely applied to the contraception due to its properties,such as its low pregnancy rate,low dropout rate,high utilization rate,and high efficiency.However,the release of copper ions in the initial stage of copper-loaded IUD implantation and the formation of calcified deposits on the surface of IUD have adverse effects to the user,such as waist and abdomen pain,gynecological inflammation,abnormal bleeding,menstrual disorders,menorrhagia and Increased secretions.In addition,the high concentration of zinc ions can completely immobilize the sperm in a short time and cannot be fertilized with the egg,and the zinc ion can inhibit the spermatozoon’s radiation crown penetrating enzyme and prevent from fertilization.Many studies have shown that zinc materials have a contraceptive effect.With the development of industrial technology,zinc materials have also been developed,such as several studies on vascular stents.In this study,we will explore the application of zinc materials in IUD and hope to promote the application of IUD.This study utilized the degradability of magnesium and its alloys and the anti-fertility effects of zinc materials to improve the adverse reactions of IUD.The in vitro corrosion properties,cell compatibility and histocompatibility of the materials were investigated.The main results are as follows:1.The corrosion rate of Mg-1Ca in SUFs at pH 6.0,7.0,and 7.9 is significantly higher than Mg-2Zn and HP-Mg measured by immersion experiment and electrochemical experiment.Corrosion rate at the end of the 120d soaking period,Mg-2Zn>HP-Mg.The corrosion products deposited on the surface of the material were observed by SEM and found that the surface of Mg-1Ca deposited more corrosion products and showed a dense corrosion layer.On the surface of hp-mg,a loose corrosion layer is formed.Through the corrosion layer,it can be seen that the base corrosion products of Mg mainly include Mg（OH）₂ and CaCO₃/CaCO₃·H₂O。2.CCK8 cytotoxicity experiments showed that HP-Mg,Mg-1Ca and Mg-2Zn had no toxic effects on four intrauterine cells and had good cytocompatibility.Compared with HP-Mg and Mg-2Zn,Mg-1Ca significantly promoted proliferation of endometrial epithelial cells,endometrial smooth muscle cells and endometrial stromal cells for 5 days.3.The concentration of Mg²⁺ in the cell culture medium extracts of HP-Mg,Mg-1Ca and Mg-2Zn is 4-6 times higher than that of the control（not soaking material）medium,and the gene expression results show that Mg²⁺transport Protein expression was significantly up-regulated;for the detection of inflammatory factors,we found that Mg-2Zn promoted the expression of inflammatory factors in cells,while HP-Mg and Mg-1Ca inhibited the expression of inflammatory factors.4.Animal experiments show that HP-Mg,Mg-1Ca and Mg-2Zn have good tissue compatibility,and an acute inflammatory reaction occurs in the early stage of implantation,which changes to a chronic inflammatory response with prolonged implantation time.It reacted slightly with the tissue at the end of the month and was covered with a layer of connective tissue.5.The corrosion rate of pure Zn material in SUF is significantly higher than that of Zn-0.1Li and Zn-0.8Mg.The release rate of ion release in the early stage is also significantly higher than that of Zn-0.1Li and Zn-0.8Mg.Surface corrosion products were found to have pitting and corrosion pits by SEM observation.The corrosion products were mainly analyzed by XRD pattern of ZnO,Zn（OH）₂,CaPO₃（OH）,Zn₂P₂O₇·2H₂O.6.Cytotoxicity tests showed that Zn-0.1Li and Zn-0.8Mg could significantly improve the toxic effects of pure Zn on endometrial epithelial cells and endometrial stromal cells.7.Animal in situ implantation experiments showed that pure Zn,Zn-0.1Li and Zn-0.8Mg were mainly acute inflammatory reactions in the early stage after implantation,and gradually changed into chronic inflammatory reaction with prolonged implantation time,but did not cause endometrial abnomalities or become cancerous.8.The mainly corrosion products were ZnO after implantion in animal uterine.（Ca,Mg）CO₃ was apper in later implantion time.In this paper,it is proved that magnesium alloy has good biocompatibility.Compared with HP-Mg and Mg-2Zn,Mg-1Ca alloy has a faster degradation rate in vitro.In addition,the retro time of uterus is about 42 days,and Mg-1Ca is expected to become a suitable material for IUD fixation device.Zn-0.1Li and Zn-0.8Mg alloys can significantly improve the cellular compatibility of pure zinc to intrauterine cells and the histocompatibility of endometrium.