In vitro biological evaluations are important in developing and clinically approving biodegradable magnesium (Mg)-based devices. However, such methods specified in ISO Standards for these in vitro evaluations are flawed. The particular concern is the excessive inhibition of Mg extracts on cells and bacteria, attributed to the increased pH value and Mg²⁺ concentration due to Mg degradation. To figure out this issue, the current investigation detailed the coupling impact of these two factors on the viability of normal cells, tumor cells and bacteria. The results showed that the response of cells and bacteria to Mg²⁺ heavily depended on the medium pH value. Normal human dermal fibroblasts (NHDF) and human non-small-cell lung cancer cells (H23) exhibited a high tolerance to Mg²⁺ under the neutral condition, while human umbilical vein endothelial cells (HUVEC) under the alkaline condition. The alkaline condition coupled with increased Mg²⁺ concentrations could produce antibacterial effects against Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli), while the tolerance of these two bacteria to Mg²⁺ at different pH values was also different. The overlap analysis on the survival predominant regions of these cells and bacteria indicated that Mg degradation could not achieve a win-win situation of antisepsis and the safety of the two normal cells by affecting the medium pH value and Mg²⁺ concentration. However, increasing Mg²⁺ concentration and pH might have anti-H23 effects without inducing cytotoxicity to NHDF and/or HUVEC cells. Based on these results, a recommendation to evaluate the biological effects of magnesium-based materials in terms of their interfacial characteristics during degradation and associated key environmental thresholds influencing the behavior of cells and bacteria was proposed.

Biodegradable metals have been of great interest in making gastrointestinal implants these years. The most researched biodegradable metal is magnesium (Mg), followed by zinc (Zn) and iron (Fe). However, due to the limitations of in vivo experiments and the complex component of the gastrointestinal fluid, their degradation mechanisms in such an environment are still ambiguous. In this work, the human duodenal fluid (HDF) was used to investigate their in vitro degradation behaviors, with a simulated duodenal fluid (SDF) prepared for the control group based on the HDF ionic composition. After immersion of these metals for 7 days, it is found that HDF shows a stronger pH buffering effect than SDF due to the presence of organics. These organics can also hinder the degradation of metals by affecting their product formation in different ways. On the one hand, the adsorption of organics and their effects on the fluid dominate their degradation inhibition effect on Mg and Zn in HDF. On the other hand, they can hinder the further oxidation of the degradation products of Fe, which is the main mechanism resulting in a lower degradation rate of Fe in HDF rather than in SDF. Among the three metals, Mg unsurprisingly shows the highest degradation rate in both fluids. Interestingly, Zn is nearly immune to degradation in HDF, while it presents typical pitting corrosion in SDF. Compared to their degradation rates in popular pseudo-humoral media (e. g. Hanks’ Balanced Salt Solutions, Dulbecco’s modified Eagle’s medium) reported previously, Mg degrades faster, and Zn and Fe more slowly in HDF. The higher in vitro degradation rate of Fe than that of Zn is influenced by oxygen and ions in the degradation environment.