The increased ratio of Mg2+/Ca2+ from degrading magnesium alloys directs macrophage fate for functionalized growth of endothelial cells

Biomedical magnesium (Mg) alloys have been widely studied as important structural materials and biodegradable materials in cardiovascular stents system. However, excessively rapid degradation and delayed endothelialization are still the bottlenecks limiting the further application of Mg alloy stents. The core scientific problem lies in how Mg alloys and their degradation products direct the fate of cardiovascular cells to develop in favor of endothelialization, which is still unclear. The aggregation of macrophages (MA) is the earliest cellular response after stent implantation for atherosclerotic lesions, and our previous research proved that MA behaviors played crucial roles on endothelialization in vitro. Thus, the present study chooses a Mg alloy, Mg–Zn–Y-Nd, to investigate its degradation behavior on directing the fates of MA and endothelial cells (EC). Our data shows that the increased ratio of Mg²⁺/Ca²⁺ in medium during the degradation of the Mg–Zn–Y-Nd alloy may regulate the MA to switch to their M2 phenotype, and the MA conditioned medium further promote the proliferation and CD31 expression of EC in vitro. Co-culture of MA and EC indicates that M2-type MA also contribute to proliferation and CD31 expression of EC. All these results suggest controlling the degradation behavior of Mg alloys will direct the fates of MA and EC, further improving endothelialization in vitro.