Responses of human urothelial cells to magnesium-zinc-strontium alloys and associated insoluble degradation products for urological stent applications.

Current urological devices such as ureteral stents and catheters still face serious problems, such as encrustation and biofilm formation. Magnesium (Mg) and its alloys showed great potentials as an alternative material for urological devices, due to their excellent biodegradability and antibacterial property. In this study, a serial of four promising Mg alloys which contain zinc (Zn) and strontium (Sr), i.e., Mg-4Zn-xSr (ZSr41) alloys, were investigated in vitro for potential ureteral stent application. Specifically, these four alloys have 4 wt% Zn in all and 0.15 wt% Sr in ZSr41_A, 0.5 wt% Sr in ZSr41_B, 1.0 wt% Sr in ZSr41_C and 1.5 wt% Sr in ZSr41_D. The cytocompatibility and degradation behaviors of Mg-4Zn-xSr alloys were studied by culturing with human urothelial cells (HUCs) for 24 h and 48 h using exposure culture method. ZSr41_B showed a better cytocompatibility with HUCs among all the Mg-4Zn-xSr alloys in both 24-hour and 48-hour cultures. Moreover, the cytocompatibility of insoluble degradation products of Mg, i.e., MgO and Mg(OH)2, was also investigated by culturing different concentrations of MgO and Mg(OH)2 nanoparticles with HUCs for 24 h and 48 h. The concentration of MgO and Mg(OH)2 particles at 0.5 mg/mL and above, showed a significant decrease of cell density and cell size after 24-hour and 48-hour cultures. The concentration of MgO and Mg(OH)2 at 1.0 mg/mL and above, showed no viable cells after 24-hour culture. Collectively, it is recommended to further reduce the degradation rates of Mg alloys in order to control possible side effects of the soluble and insoluble degradation products and to take the benefits of Mg-based biodegradable ureteral stents toward the future clinical translation.

Cytocompatibility of Magnesium Alloys with Human Urothelial Cells: A Comparison of Three Culture Methodologies.

Magnesium (Mg) is a biodegradable metallic material, which has shown great potential for medical device applications. In this study, human urothelial cells (HUCs) were cultured in vitro with Mg-based substrates to investigate their cytocompatibility for potential urological device applications. Three different in vitro culture methodologies were explored to mimic different in vivo conditions, in an attempt to establish standard methods of evaluating cytocompatibility of Mg-based biomaterials for urological device applications. Direct culture is a suitable in vitro method when it is important to evaluate direct cell attachment on the biomaterial surfaces. Direct exposure culture is a desirable in vitro method for investigating the response of well-established cells in the body with newly implanted biomaterials. The exposure culture method is appropriate for evaluating cell-biomaterial interactions in the same environment, where they are not in direct contact with each other. The results showed differences in HUC behaviors with the same Mg-based substrates when different culture methods were used. The Mg-based substrates inhibited the HUC viability with direct contact at the cell-material interface in direct culture and direct exposure culture. The faster degrading Mg alloys containing yttrium reduced HUC density in direct culture, direct exposure culture, and exposure culture. The major soluble degradation products of Mg-based materials reduced HUC density significantly when the pH increased to 8.6 and above or the Mg2+ ion concentration reached 10 mM and above. Mg-based biomaterials, especially the slower degrading alloys such as AZ31, should be further studied to determine their potential to be used for bioresorbable urological devices.