Feasibility evaluation of a Cu-38 Zn alloy for intrauterine devices: In vitro and in vivo studies

Abstract

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 (Cu²⁺) 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 Cu²⁺ 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 (Cu²⁺) 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 Cu²⁺ 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.

Keywords: Biocompatibility; Burst release; Copper-containing intrauterine devices; Corrosion behavior; Cu-Zn alloy; Simulated uterine fluid.