Department of Reproduction and Physiology, National Research Institute for Family Planning, Beijing 100081, China; Graduate School of Peking Union Medical College, Beijing 100730, China.
Department of Reproduction and Physiology, National Research Institute for Family Planning, Beijing 100081, China.
Acta Biomater. 2022 Jan 15;138:561-575. doi: 10.1016/j.actbio.2021.11.006. Epub 2021 Nov 11.
The existing adverse effects of copper in copper-containing intrauterine devices (Cu-IUDs) have raised concerns regarding their use. These adverse effects include burst release of cupric ions (Cu) at the initial stage and an increasingly rough surface of the Cu-IUDs. In this study, we investigated the use of two copper alloys, Cu-38 Zn and H62 as the new upgrading or alternative material for IUDs. Their corrosive properties were studied in simulated uterine fluid (SUF) by using electrochemical methods, with pure Cu as a control. We studied the in vitro long-term corrosion behaviors in SUF, cytotoxicity to uterine cells (human endometrial epithelial cells and human endometrial stromal cells), in vivo biocompatibility and contraceptive efficacy of pure Cu, H62, and Cu-38 Zn. In the first month, the burst release rate of Cu in the Cu-38 Zn group was significantly lower than those in the pure Cu and H62 groups. The in vitro cytocompatibility Cu-38 Zn was better than that of pure Cu and H62. Moreover, Cu-38 Zn showed improved tissue biocompatibility in vivo experiments. Therefore, the contraceptive efficacy of the Cu-38 Zn is still maintained as high as the pure Cu while the adverse effects are significantly eased, suggesting that Cu-38 Zn can be a suitable potential candidate material for IUDs. STATEMENT OF SIGNIFICANCE: The existing adverse effects associated with the intrinsic properties of copper materials for copper-containing intrauterine devices (Cu-IUD) are of concern in their employment. Such as, burst release of cupric ions (Cu) at the initial stage and an increasingly rough surface of the Cu-IUD. In this work, Cu alloyed with a high amount of bioactive Zn was used for a Cu-IUD. The Cu-38 Zn alloy exhibited reduced burst release of Cu within the first month compared with the pure Cu and H62. Furthermore, the Cu-38 Zn alloy displayed significantly improved biocompatibility and a much smoother surface. Therefore, high antifertility efficacy of the Cu-38 Zn alloy was well maintained, while the adverse effects are significantly eased, suggesting that the Cu-38 Zn alloy is promising for a Cu-IUD.
现有的含铜宫内节育器（Cu-IUD）中铜的不良影响引起了人们对其使用的关注。这些不良影响包括铜离子（Cu）在初始阶段的爆发释放和 Cu-IUD 表面越来越粗糙。在这项研究中，我们研究了两种铜合金，Cu-38Zn 和 H62，作为 IUD 升级或替代材料。我们使用电化学方法在模拟子宫液（SUF）中研究了它们的腐蚀性，以纯铜作为对照。我们研究了 SUF 中体外长期腐蚀行为、对子宫细胞（人子宫内膜上皮细胞和人子宫内膜基质细胞）的细胞毒性、体内生物相容性和纯铜、H62 和 Cu-38Zn 的避孕效果。在第一个月，Cu-38Zn 组的 Cu 爆发释放率明显低于纯铜和 H62 组。体外细胞相容性 Cu-38Zn 优于纯铜和 H62。此外，Cu-38Zn 在体内实验中表现出更好的组织生物相容性。因此，Cu-38Zn 的避孕效果仍然保持与纯铜一样高，而不良影响明显减轻，表明 Cu-38Zn 可以成为一种合适的潜在宫内节育器候选材料。
与含铜宫内节育器（Cu-IUD）铜材料固有特性相关的现有不良影响在其应用中受到关注。例如，铜离子（Cu）在初始阶段的爆发释放和 Cu-IUD 表面越来越粗糙。在这项工作中，使用高生物活性锌合金化的铜来制造 Cu-IUD。与纯铜和 H62 相比，Cu-38Zn 合金在第一个月内 Cu 的爆发释放减少。此外，Cu-38Zn 合金显示出明显改善的生物相容性和更光滑的表面。因此，Cu-38Zn 合金保持了较高的避孕效果，同时不良影响明显减轻，表明 Cu-38Zn 合金有望用于 Cu-IUD。
