Evaluation of short-term effects of rare earth and other elements used in magnesium alloys on primary cells and cell lines

TLDR: Of the elements with high solubility in magnesium alloys, Gd and Dy seem to be more suitable than Y, and La and Ce showed the highest cytotoxicity of the analysed elements.

About: This article is published in Acta Biomaterialia.The article was published on 2010-05-01 and is currently open access. It has received 487 citations till now. The article focuses on the topics: Magnesium alloy & Magnesium.

Figures

Table 1: Contents of different rare earth elements and impurities (in italics) in different hardeners (Unit: mg/Kg).

Table 4: Summarized features of the tested rare earth elements. Positive influences (+), intermediate influences (+-), negative influences (-) and significant effects (--) on the applied test systems are indicated (n/a – no results for the apoptosis test). Additionally the LD50 values derived from literature are given. Elements with high solid solubility are highlighted in grey.

Table 3: Viability of macrophages, osteoblast-like cells and stem cells exposed to different rare earth elements up to concentrations of 2 mM. Given are the initial inhibitory concentration (IIC), which is described as the first statistically significant drop in viability compared to the control and the lethal dose 50 (LD50). n/a = no effect in the measured concentration range.

Table 2: Concentrations of selected elements present in a commercially available WE43 magnesium alloy. Values are means of three independent measurements by ICP-OES. Elements analysed in this study are highlighted in grey.

Frequently asked questions

Q1. What are the contributions in this paper?

Magnesium alloys were also investigated for orthopaedic applications this paper, where they can be applied in various designs e.g. as screws, plates or other fixture devices. 

Q2. What are the future works in this paper?

Further studies examining the influence of such concentrations on the intracellular magnesium are currently performed. From the material aspect, the combination of zirconium and yttrium as zirconia ceramic for femoral heads led to catastrophic failure of several hundred implants in 2001 and induced a discussion about the future of such biomaterials 39. It also may influence the degradation in a positive manner, but this assumption needs further detailed investigations. For all elements with low solubility there is the indispensable need for further insights into the release by a degrading alloy and accumulation kinetics in the body. 

Q3. What is the role of lithium in magnesium stents?

Lithium enhances ductility and formability of magnesium alloys by changing the lattice structure from hexagonal close-packed to body-centered cubic. 

Q4. What are the suitable elements for magnesium alloy development?

For magnesium alloy development the highly soluble Dy and Gd seem to be more suitable than Y. Suitable elements with low solid solubility could be Eu, Nd and Pr. If not avoidable La and Ce, should be used cautiously. 

Q5. What is the purpose of REE in magnesium alloys?

The original field of REE application is in transportation industries where they are used to improve creep and corrosion resistance and to increase the materials service temperature. 

Q6. What is the way to test the apoptosis of primary osteoblasts?

in the long run magnesium and its alloys suitable for orthopaedic applications should be tested in a non-static co-culture of primary osteoblasts and osteoclasts. 

Q7. What was the drift of the instrument?

The measurements were performed using a modified bracketing procedure, although the drift of the instrument did not exceed 1.5 % during the day and therefore a drift correction was not necessarily required. 

Q8. What is the effect of a lanthanum containing compound on cancer cells?

General effects of Motefaxin gadolinium on cancer cells 27 were observed as well as the activity of a lanthanum containing compound against more than 60 tumor models 36. 

Q9. What is the need for further research into the release by a degrading alloy?

For all elements with low solubility there is the indispensable need for further insights into the release by a degrading alloy and accumulation kinetics in the body. 

Q10. What is the maximum amount of Ca in the WE43 analysis?

In magnesium alloying Ca belongs to the elements with low solid solubility and therefore the amount of possible Ca addition is limited to 0.82 wt% 20. 

Q11. What was the sigmoidal curve for MG63?

RAW showed a typical sigmoidal curve progression (R2=0.9722, p<0.001), whereas MG63 followed a nearly linear dependency up to complete cell death at 100 mM MgCl2 (R2=0.9877, p<0.001). 

Q12. What was the pronounced induction of apoptosis?

The most pronounced induction of apoptosis was induced by Gadolinium followed by neodymium, while the other elements only showed a moderate increase (figure 7). 

Q13. Why was calcium chosen for the WE43 analysis?

Calcium was not only chosen due to its appearance in the WE43 analysis (table 2), but also as important and essential cation with even higher involvement in cellular processes than magnesium. 

Q14. What are the advanced clinical applications of magnesium stents?

magnesium alloys for magnesium stents (WE43; W=Yttrium, E=rare earths), are containing rare earth element (REE) mixtures based on neodymium or cerium as hardeners. 

Q15. What is the robust assay system for HUCPV?

From the analyses of Mg and Ca it can be stated that RAW 264.7 are the most sensitive cells for the influence of salts and HUCPV tended to be the most robust cellular assay system. 

Q16. How long does Eu take to die?

also in in vivo studies surprising results can occur, as the i.v. administration of Eu in lower doses in rabbits leads to spontaneous death with in a short time (pers. Comm.