Dong Li, Zhang Guangde, Shen Zhiyuan, Hong Xiaojian, Xing Yongli, Wu Yue, Yang Wei, Zhang Binmei, Shi Zhiyu
Department of Cardiology, The Fourth Affiliated Hospital of Harbin Medical University, Harbin 150001, China.
Department of Medical Imaging, Second Hospital of Harbin, Harbin 150056, China.
ACS Omega. 2025 Apr 25;10(17):17280-17295. doi: 10.1021/acsomega.4c09349. eCollection 2025 May 6.
Due to their biocompatibility, biodegradability, and suitable mechanical properties, magnesium-based biodegradable implants are emerging as a promising alternative to traditional metal implants. The Mg-4Y-3RE (WE43) biodegradable alloy is among the most extensively studied and widely utilized magnesium alloys in clinical applications. As an absorbable and degradable metallic material, magnesium alloys undergo gradual degradation, wear, and fracture within the body. These alloys reduce the long-term risks associated with permanent implants but generate insoluble byproducts that accumulate in surrounding tissues. Following the implantation of magnesium alloys, granulation tissue and fibrous encapsulation typically form around the material. However, limited research has addressed the interaction between insoluble byproducts of magnesium alloys and macrophages. This study focused on the biological effects of macrophages during the second stage of the host inflammatory response in the degradation process of magnesium alloy. Using subcutaneous implantation of WE43 magnesium alloy sheets, observations were made regarding the degradation components, morphological changes in surrounding tissues, and the biological effects of macrophages upon phagocytosis of insoluble byproducts. The primary degradation products of WE43 in vivo were identified as Ca (PO), Mg(PO), NaPO, NaCa (PO), MgSO, MgCO, NaCl, Mg24Y5, and Mg12YNd. Postimplantation, levels of IL-1β and IL-18 in adjacent tissues significantly increased ( < 0.05). By 8 weeks, compared to nitinol alloy, significant thickening of the fibrous capsule ( < 0.05) was observed, accompanied by substantial inflammatory cell infiltration, vascularization, and the presence of macrophages and multinucleated giant cells. Macrophages were observed extending pseudopodia to enclose and phagocytose particles, forming phagosomes and creating a relatively isolated microenvironment around the engulfed substances, where further particle degradation occurred. Following the phagocytosis of degradation products, macrophages exhibited increased lysosome numbers, mitochondrial swelling and damage, phagolysosome formation, and autophagosome development. Furthermore, the degradation products were observed to induce elevated reactive oxygen species (ROS) production in macrophages, activation of P2X7 receptors, enhanced IL-6 secretion, endoplasmic reticulum stress, autophagy, and activation of the NLRP3 inflammasome pathway. This study provides novel insights and contributes a theoretical foundation for a more comprehensive understanding of magnesium alloy degradation in vivo.
由于其生物相容性、生物可降解性和合适的机械性能，镁基可生物降解植入物正成为传统金属植入物的一种有前途的替代品。Mg-4Y-3RE（WE43）可生物降解合金是临床应用中研究最广泛、使用最普遍的镁合金之一。作为一种可吸收和可降解的金属材料，镁合金在体内会逐渐降解、磨损和断裂。这些合金降低了与永久性植入物相关的长期风险，但会产生不溶性副产物并在周围组织中积累。镁合金植入后，通常会在材料周围形成肉芽组织和纤维包膜。然而，关于镁合金不溶性副产物与巨噬细胞之间相互作用的研究有限。本研究聚焦于巨噬细胞在镁合金降解过程中宿主炎症反应第二阶段的生物学效应。通过皮下植入WE43镁合金片，观察了降解成分、周围组织的形态变化以及巨噬细胞吞噬不溶性副产物后的生物学效应。WE43在体内的主要降解产物被鉴定为Ca(PO)、Mg(PO)、NaPO、NaCa(PO)、MgSO、MgCO、NaCl、Mg24Y5和Mg12YNd。植入后，相邻组织中IL-1β和IL-18水平显著升高（<0.05）。到8周时，与镍钛诺合金相比，观察到纤维囊显著增厚（<0.05），伴有大量炎性细胞浸润、血管形成以及巨噬细胞和多核巨细胞的存在。观察到巨噬细胞伸出伪足包裹并吞噬颗粒，形成吞噬体，并在被吞噬物质周围形成相对隔离的微环境，在其中发生进一步的颗粒降解。吞噬降解产物后，巨噬细胞表现出溶酶体数量增加、线粒体肿胀和损伤、吞噬溶酶体形成以及自噬体发育。此外，观察到降解产物可诱导巨噬细胞中活性氧（ROS）生成增加、P2X7受体激活、IL-6分泌增强、内质网应激、自噬以及NLRP3炎性小体途径激活。本研究提供了新的见解，并为更全面理解镁合金在体内的降解提供了理论基础。
