In Vitro Biocompatibility And Surface Modification Study Of Mg-Zn-Y-Nd Alloy For Vascular Stent Application

Coronary stents develop from bare metal stents to drug-eluting stents recent decades, which have improved immediate and late results of balloon angioplasty by tacking up dissections and preventing wall recoil. However, these current technology stents will permanently remain in the artery with many limitations including the need for long-term antiplatelet treatment to avoid thrombosis. Biodegradable Mg-based alloy cardiovascular stents have been developed to overcome those limitations. The first-in-man trial of drug-eluting absorbable metal stent (DREAMS; Biotronik, Bulach, Switzerland) has been done. The results show feasibility, good safety profile of DREAMS. Now, it is urgent for us to develop biodegradable Mg-based alloy stents with independent intellectual property rights.Another kind of biodegradable Mg-based alloy for cardiovascular stents-Mg-2Zn-0.5Y-0.5Nd alloy (Mg-Zn-Y-Nd alloy in this paper) developed by Zhengzhou University with excellent mechanical property, also meets the cardiovascular stents requirements on strength and plasticity. Before its clinical application as vascular stent material, the biocompatibility of Mg-Zn-Y-Nd alloy must be evaluated in vitro and in vivo, especially the effects on vascular endothelial and smooth muscle cells about vascular endothelialization and restenosis. What’s more, all the Mg-based alloys have the shortcoming that their degradation rate is too rapid in vivo, which would not match the healing rates of the host tissues. Therefore, this paper focuses on the interaction between Mg-Zn-Y-Nd alloy and vascular endothelial along with smooth muscle cells in vitro and the surface modification of Mg-Zn-Y-Nd alloy to control its degradation rate. The main work is divided into three parts as follows:(1) Indirect-contact study of Mg-Zn-Y-Nd alloy effects on vascular endothelial and smooth muscle cellsRecently more and more researchers query the predictability of cytotoxicity results of biomedical Mg alloys obtained according to ISO10993due to significant difference between in vitro and in vivo corrosion. This study aimed to observe the influence of different extraction parameters (time, volume/surface ratio and medium composition) on cytotoxicity results and illustrate whether more predictable results could be obtained by adjusting the extraction parameters. The results showed that longer extraction time and smaller extraction volume/surface ratio improve the sensitivity of screening Mg materials by making inferior Mg materials release relatively more ions to the extract; and more predictable results could not be obtained by the way of simply adding bovine serum albumin (BSA) into the extraction medium to the same level in vivo or simply using fetal bovine serum (FBS) directly as extraction medium, since BSA and FBS affected the cells’ health states during the test.In this part, the Mg-Zn-Y-Nd alloy was extracted according to ISO10993-12and the extract was used to culture vascular endothelial and smooth muscle cells, to study the indirect-contact influence of Mg-Zn-Y-Nd alloy to them. At the same time, to evaluate potential role of high-local degradation product concentrations to cells, all the chloride salts of Mg-Zn-Y-Nd alloy component elements were also added to the culture medium. The results show that the extract of Mg-Zn-Y-Nd alloy has no significant influence on cytotoxicity, cell migration, cell chemotaxis and Nitric Oxcide(NO) release of vascular endothelial and smooth muscle cells. As to each component elements, it is found that:when Mg reaches to a certain concentration the endothelial cell migration and NO release are promoted; Zn is the most toxic to both kinds of cells and exhibits the strongest inhibitory effect on NO release of endothelial cells among the four elements; All the four elements inhibit the migration of vascular smooth muscle cells and smooth muscle cells do not exhibit chemotaxis to them; High concentration of Y and Nd will improve endothelial cells secret more NO.(2) Direct-contact study of the interaction between Mg-Zn-Y-Nd alloy and vascular endothelial along with smooth muscle cellsIn this part, vascular endothelial and smooth muscle cells were seeded directly on the surface of Mg-Zn-Y-Nd alloy, to evaluate the interaction between Mg-Zn-Y-Nd alloy and vascular endothelial along with smooth muscle cells including cell attachment, ion concentrations viariation and Mg-Zn-Y-Nd alloy surface corrosion layer components change. The results show that vascular smooth muscle cells grew better than endothelial cells on the surface of Mg-Zn-Y-Nd alloy, hinting that the surface modification of alloy is necessary to inhibit the smooth muscle cell proliferation. On the other hand, both endothelial and smooth muscle cells facilitated the degradation of Mg-Zn-Y-Nd alloy. The more cells grew on the alloy, the alloy degraded faster.(3) Surface modification of Mg-Zn-Y-Nd alloyAn anti-corrosion and quick re-endothelialization surface coating was successfully fabricated on biodegradable Mg-Zn-Y-Nd alloy by a simple two-step immersion method with low cost, first in HF and then in dopamine solution. The HF-PDA-treated Mg alloy showed dramatic improvement in corrosion resistance in (DMEM+40g/L BSA) solution in cell culture condition by electrochemical tests and immersion degradation tests for14d. HF-PDA-treated surface layer enhanced the vascular cells’ adhesion and proliferation as anticipated.In summary, the novel Mg-Zn-Y-Nd alloy with independent intellectual property rights exhibits excellent biocompatibility to vascular endothelial and smooth muscle cells in vitro. HF-PDA-treated Mg-Zn-Y-Nd alloy has greater potential in application of biodegradable cardiovascular stents.