In vitro and in vivo studies on magnesium alloys to evaluate the feasibility of their use in obstetrics and gynecology

Abstract

Magnesium and its alloys were widely investigated in many body fluid microenvironments including bone, blood, bile, saliva, and urine; however, no study has been conducted in the intrauterine microenvironment. In this study, the degradation behaviors of HP-Mg, Mg-1Ca, and Mg-2Zn alloys in simulated uterine fluid (SUF) were systematically investigated, and then the biological response of four kinds of uterine cells to these materials was observed. For this purpose, the gluteal muscle of rat was used as the implantation position to study the in vivo biocompatibility as a mimic of the intrauterine device (IUD) fixation part. The 120-day immersion test indicated that the Mg-1Ca alloy had a faster degradation rate than the Mg-2Zn alloy and HP-Mg and dissolved entirely in the SUF. Indirect cytotoxicity assay showed that the extracts of HP-Mg, Mg-1Ca, and Mg-2Zn alloys have positive effects on human uterine smooth muscle cells (HUSMC), human endometrial epithelial cells (HEEC), and human endometrial stromal cells (HESC), especially for the Mg-1Ca alloy group. Furthermore, the in vivo experiment showed that HP-Mg, Mg-1Ca, and Mg-2Zn alloy implants cause a light inflammatory response in the initial 3 days, but they were surrounded mainly by connective tissue, and lymphocytes were rarely observed at 4 weeks. Based on the above facts, we believed that it is feasible for using biomedical Mg alloys in obstetrics and gynecology and proposed three kinds of medical device candidates for future R&D. Statement of Significance Magnesium alloys were widely investigated in various body microenvironments including bone, blood, bile, saliva, and urine; however, no study has been conducted in the intrauterine environment. In this work, the degradation behaviors of Mg alloys in simulated uterine fluid were systematically investigated, and then the biological response of four kinds of uterine cells to these materials was observed. For this purpose, the tibialis anterior of a rat model was used as the implantation position to study the in vivo biocompatibility. The comprehensive in vitro and in vivo testing results indicated that biomedical Mg alloys are feasible for use in obstetrics and gynecology. Further, three kinds of medical device candidates were proposed.

Keywords: Biodegradable metals; Intrauterine microenvironment; Magnesium alloys; Obstetrics and gynecology; Simulated uterine fluid.