Mg-Y-Nd alloy biocorrosion behavior in hyperlipidemia models in vitro and in vivo

The permanent nature of bare metal and drug eluting stents can lead to serious long-term complications such as neoatherosclerosis and late stent thrombosis. Magnesium (Mg) based bioabsorbable metal stents, with the ability to provide temporary support to stenosed arteries and harmlessly degrade, are in position to be the 4^th revolution of interventional cardiology. Mg materials are known to be sensitive to biological factors, however this has been understudied with respect to hyperlipidemia. In this study, two distinct WE-series (Mg-Y-Nd) alloy wires (WE43 and WE22) were implanted into the abdominal aorta of wild-type and hyperlipidemic apolipoprotein E knockout (ApoE^-/-) mice for 10 days to investigate the acute corrosion response. We report increased corrosion in ApoE^-/- mice for both alloys, resulting in wire breakage for 50% of WE43 (n=4) and 75% of WE22 implants (n=4) in ApoE^-/- mice compared to 0% in wild-type mice for each alloy (n = 4 WE43 and n=4 WE22). Additionally, human low- and high-density (LDL/HDL) lipoproteins were used to study the in vitro corrosion behavior of WE-series alloys. We report increased acute corrosion of WE43 (6.2 ± 0.7 mm/yr in lipoprotein-supplemented DMEM vs 1.5 ± 0.3 mm/yr in DMEM) and decreased Ca and Mg in the oxide layer of wires corroded in lipoprotein-supplemented medium. Here, LDL and HDL are shown to impact Mg alloy biocorrosion in a dose- and species-dependent manner. Based on our observations, we propose a general mechanism for lipoprotein-mediated Mg corrosion driven by differential chelation of alloying elements specific to each lipoprotein species. STATEMENT OF SIGNIFICANCE: Patients with narrowed or blocked arteries currently receive permanent metal stents, which can lead to long-term complications such as in-stent restenosis and neoatherosclerosis. Bioabsorbable magnesium (Mg) stents degrade over time, reducing the long-term risks, however studies show these materials are sensitive to biological factors. The interactions between cholesterol, which is often increased in patients with atherosclerosis, and Mg-based materials have not been studied. In this study, clinically relevant Mg-alloys are implanted in hyperlipidemic apolipoprotein E knockout mice to investigate the role of increased cholesterol on Mg biocorrosion in vivo. Human low- and high-density lipoproteins are used to investigate the role of lipoproteins on clinically relevant Mg-alloy biocorrosion in vitro.