WE43镁合金的体内降解及其在巨噬细胞上的降解产物

IF 4.3 3区 化学 Q2 CHEMISTRY, MULTIDISCIPLINARY
ACS Omega Pub Date : 2025-04-25 eCollection Date: 2025-05-06 DOI:10.1021/acsomega.4c09349
Li Dong, Guangde Zhang, Zhiyuan Shen, Xiaojian Hong, Yongli Xing, Yue Wu, Wei Yang, Binmei Zhang, Zhiyu Shi
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引用次数: 0

摘要

由于其生物相容性、生物可降解性和合适的机械性能,镁基生物可降解植入物正成为传统金属植入物的一个有前途的替代品。Mg-4Y-3RE (WE43)可生物降解镁合金是研究最广泛、临床应用最广泛的镁合金之一。镁合金作为一种可吸收和可降解的金属材料,在体内会逐渐降解、磨损和断裂。这些合金降低了与永久植入物相关的长期风险,但会产生不溶性副产物,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封。然而,有限的研究已经解决了镁合金的不溶性副产品和巨噬细胞之间的相互作用。本研究重点研究了镁合金降解过程中巨噬细胞在宿主炎症反应第二阶段的生物学作用。通过皮下植入WE43镁合金片,观察其降解组分、周围组织形态变化以及巨噬细胞吞噬不溶性副产物的生物学效应。WE43在体内的主要降解产物为Ca3 (PO4)2、Mg3(PO4)2、Na3PO4、NaCa (PO4)、MgSO4、MgCO3、NaCl、Mg24Y5和Mg12YNd。移植后邻近组织IL-1β和IL-18水平显著升高(p < 0.05)。8周时,与镍钛诺合金相比,纤维囊明显增厚(p < 0.05),伴有大量炎症细胞浸润、血管化、巨噬细胞和多核巨细胞的出现。观察到巨噬细胞伸出假足包裹吞噬颗粒,形成吞噬体,在被吞噬物质周围形成相对孤立的微环境,颗粒进一步降解。降解产物被吞噬后,巨噬细胞表现出溶酶体数量增加、线粒体肿胀和损伤、吞噬酶体形成和自噬体发育。此外,降解产物可诱导巨噬细胞活性氧(ROS)产生升高、P2X7受体激活、IL-6分泌增强、内质网应激、自噬和NLRP3炎症小体通路激活。该研究提供了新的见解,为更全面地了解镁合金在体内的降解提供了理论基础。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Degradation of WE43 Magnesium Alloy in Vivo and Its Degradation Products on Macrophages.

Degradation of WE43 Magnesium Alloy in Vivo and Its Degradation Products on Macrophages.

Degradation of WE43 Magnesium Alloy in Vivo and Its Degradation Products on Macrophages.

Degradation of WE43 Magnesium Alloy in Vivo and Its Degradation Products on Macrophages.

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 Ca3 (PO4)2, Mg3(PO4)2, Na3PO4, NaCa (PO4), MgSO4, MgCO3, NaCl, Mg24Y5, and Mg12YNd. Postimplantation, levels of IL-1β and IL-18 in adjacent tissues significantly increased (p < 0.05). By 8 weeks, compared to nitinol alloy, significant thickening of the fibrous capsule (p < 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.

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来源期刊
ACS Omega
ACS Omega Chemical Engineering-General Chemical Engineering
CiteScore
6.60
自引率
4.90%
发文量
3945
审稿时长
2.4 months
期刊介绍: ACS Omega is an open-access global publication for scientific articles that describe new findings in chemistry and interfacing areas of science, without any perceived evaluation of immediate impact.
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