Bao Guo, Wang Kun, Yang Lijun, He Jialing, He Bin, Xu Xiaoxue, Zheng Yufeng
Department of Reproduction and Physiology, National Research Institute for Family Planning, Beijing 100081, China.
Department of Reproduction and Physiology, National Research Institute for Family Planning, Beijing 100081, China; Graduate School of Peking Union Medical College, Beijing 100730, China.
Acta Biomater. 2022 Apr 1;142:374-387. doi: 10.1016/j.actbio.2022.01.053. Epub 2022 Jan 31.
The comprehensively adopted copper-containing intrauterine devices (Cu-IUDs) present typical adverse effects such as bleeding and pain at the initial stage of post-implantation. The replacement of Cu material is demanded. Zinc and its alloys, the emerging biodegradable materials, exhibited contraceptive effects since 1969. In this work, we evaluated the feasibility of bulk Zn alloys as IUD active material. Using pure Cu and pure Zn as control groups, we investigated the contraceptive performance of Zn-0.5Cu and Zn-1Cu alloys via in vitro and in vivo tests. The results showed that the main corrosion product of Zn-Cu alloys is ZnO from both in vitro and in vivo studies. CaZn(PO)·2HO is formed atop after long-term immersion in simulated uterine fluid, whereas CaCO is generally formed atop after implantation in the rat uterine environment. The cytocompatibility of the Zn-1Cu alloy was significantly higher than that of the pure Zn and pure Cu to the human endometrial epithelial cell lines. Furthermore, the in vivo results showed that the Zn-1Cu alloy presented much improved histocompatibility, least damage and the fastest recovery on endometrium structure in comparison to pure Zn, Zn-0.5Cu and pure Cu. The systematic and comparing studies suggest that Zn-1Cu alloy can be considered as a possible candidate for IUD with great biochemical and biocompatible properties as well as high contraceptive effectiveness. STATEMENT OF SIGNIFICANCE: The existing adverse effects with the intrinsic properties of copper materials for copper-containing intrauterine devices (Cu-IUD) are of concerns in their employment. Such as burst release of cupric ions (Cu) at the initial stage of the Cu-IUD. Zinc and its alloys which have been emerging as a potential biodegradable material exhibited contraceptive effects since 1969. In this study, Zn-1Cu alloys displayed significantly improved biocompatibility with human uterus cells and a decreased inflammatory response within the uterus. Therefore, high antifertility efficacy of the Zn-1Cu alloy was well maintained, while the adverse effects are significantly eased, suggesting that the Zn-1Cu alloy is promising for IUD.
广泛采用的含铜宫内节育器（Cu-IUD）在植入后的初始阶段会出现出血和疼痛等典型不良反应。因此需要更换铜材料。锌及其合金作为新兴的可生物降解材料，自1969年以来就显示出避孕效果。在这项工作中，我们评估了块状锌合金作为宫内节育器活性材料的可行性。以纯铜和纯锌作为对照组，我们通过体外和体内试验研究了Zn-0.5Cu和Zn-1Cu合金的避孕性能。结果表明，体外和体内研究均显示，Zn-Cu合金的主要腐蚀产物是ZnO。在模拟子宫液中长期浸泡后，表面会形成CaZn(PO)·2HO，而在大鼠子宫环境中植入后，表面通常会形成CaCO。Zn-1Cu合金对人子宫内膜上皮细胞系的细胞相容性显著高于纯锌和纯铜。此外，体内结果表明，与纯锌、Zn-0.5Cu和纯铜相比，Zn-1Cu合金的组织相容性有了很大改善，对子宫内膜结构的损伤最小且恢复最快。系统的比较研究表明，Zn-1Cu合金具有良好的生化和生物相容性以及较高的避孕效果，可被视为宫内节育器的一种可能候选材料。重要意义声明：含铜宫内节育器（Cu-IUD）中铜材料的固有特性所带来的现有不良反应在其应用中受到关注。例如，Cu-IUD初始阶段铜离子（Cu）的突然释放。锌及其合金作为一种潜在的可生物降解材料自1969年以来就显示出避孕效果。在本研究中，Zn-1Cu合金与人子宫细胞的生物相容性显著提高，子宫内的炎症反应减少。因此，Zn-1Cu合金在保持高抗生育效果的同时，不良反应显著减轻，表明Zn-1Cu合金有望用于宫内节育器。
