Department of Cardiology, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, China.
Department of Cardiology, The First Affiliated Hospital of Harbin Medical University, Harbin, China.
J Biomed Mater Res A. 2024 Jan;112(1):6-19. doi: 10.1002/jbm.a.37601. Epub 2023 Sep 8.
Magnesium alloys have been used to manufacture biodegradable implants, bone graft substitutes, and cardiovascular stents. WE43 was the most widely used magnesium alloy. The degradation process begins when the magnesium alloy stent is implanted in the body and comes into contact with body fluid. The degradation products include hydrogen, Mg , local alkaline environment, and unsoluble products. A large number of studies focused on Mg and pH in vitro, and in vivo of magnesium alloys, but few studies on unsoluble corrosion products (UCPs). In this study, UCPs of WE43 alloy were prepared by immersion in vitro, and their effects on macrophages were investigated. The results showed that the unsoluble corrosion products were Mg24Y5, Mg12YNd, and MgCO ·3H O, which were dose-dependent on the apoptosis and necrosis of macrophages. After phagocytosis of UCPs, macrophages mainly metabolize in lysosome, and autophagy also participates in the metabolism of UCPs. It also decreases mitochondrial membrane potential and increases lysosomes, endoplasmic reticulum stress, and P2X7 receptor activation. These will increase reactive oxygen species (ROS) in cells, activating NLRP3 inflammatory corpuscles, activating the downstream pro-IL18 and pro-IL1β, and converting it to IL-18, and IL-1β. However, its pro-inflammatory effect is far lower than that of the classical Lipopolysaccharide (LPS) pro-inflammatory pathway. This work has increased our understanding of magnesium alloy metabolism and provides new ideas for the clinical application of magnesium alloys.
镁合金已被用于制造可生物降解的植入物、骨移植替代品和心血管支架。WE43 是应用最广泛的镁合金。当镁合金支架植入体内并与体液接触时,降解过程开始。降解产物包括氢气、镁、局部碱性环境和不溶性产物。大量研究集中在镁和 pH 值的体外和体内的镁合金,但对不溶性腐蚀产物 (UCPs) 的研究较少。在这项研究中,通过体外浸泡制备 WE43 合金的不溶性腐蚀产物,并研究其对巨噬细胞的影响。结果表明,不溶性腐蚀产物为 Mg24Y5、Mg12YNd 和 MgCO·3H2O,它们对巨噬细胞的凋亡和坏死具有剂量依赖性。吞噬 UCPs 后,巨噬细胞主要在溶酶体中代谢,自噬也参与 UCPs 的代谢。它还降低线粒体膜电位,增加溶酶体、内质网应激和 P2X7 受体的激活。这将增加细胞内的活性氧物质 (ROS),激活 NLRP3 炎症小体,激活下游的 pro-IL18 和 pro-IL1β,并将其转化为 IL-18 和 IL-1β。然而,其促炎作用远低于经典脂多糖 (LPS) 促炎途径。这项工作增加了我们对镁合金代谢的理解,并为镁合金的临床应用提供了新的思路。