# How Does the Biocompatibility of Molybdenum Compare to the Gold Standard Titanium?--An In Vivo Rat
## 4 Discussion  
The results must be considered from two different points of view--biocompatibility and degradation rates. The overall aim of our experiment was to demonstrate the biocompatibility of molybdenum compared to the gold standard titanium in a complex organism. We were able to clearly demonstrate, in a statistically sufficiently large cohort, that molybdenum plates do not cause a significant inflammatory reaction after insertion into the nuchal fold when compared with the gold standard titanium. This is based on evidence from daily clinical routine examination as well as histopathological diagnostics. Using the established Krenn histopathological synovitis score, we were able to quantify our observations of reactive capsule formation and compare both cohorts. There were no significant differences between the animals with either molybdenum or titanium implants. Furthermore, in addition to the inflammatory response, the general welfare of the animals was also examined daily. Both cohorts showed normal absolute weight, as well as adequate weight gain, without significant differences between the groups. These in vivo biocompatibility results are, therefore, in line with our previously conducted experiments, in which we were already able to demonstrate the biocompatibility of molybdenum in vitro [28]. The kidneys, livers, and spleens of the rats showed no macroscopic or pathological anomalies, and especially no differences in comparison between the examined cohorts. There were no measurable deposits of molybdenum. This is particularly noteworthy for the kidneys, because the excretion of molybdenum has, so far, mainly been described renally [35]. In addition, higher doses of molybdenum intake have been described as harmful to the kidneys of rats [29]. [PERSON] et al. showed that doses of 80 mg/kg/d lead to dysfunction of the tubules and glomeruli [30]. [PERSON] et al. also reported a qualitative pathological remodeling of [PERSON]'s capsule and glomeruli of the kidney, which could be related to Mo toxicity [27]. However, we must point out that, according to metallographic examination, very little Mo was dissolved, so it is not surprising that there were no changes. However, this is not evidence that Mo cannot theoretically cause damage. So far, our biocompatibility results agree with those of [PERSON] et al. and [PERSON] et al. who also reported on the biocompatibility of molybdenum regarding the question of whether molybdenum is a potentially bioresorbable material for cardiac stents [27; 36]. Figure 11: Metallographic cross-sections of molybdenum samples. The analyses of the samples are shown from left to right in ascending order, from the reference to the 12-month sample. The upper line shows the cut sample, the middle line the 100\(\times\) magnification, and the lower line the 200\(\times\) magnification. Optical microscopy images are shown. The very low degradation of the explanted molybdenum samples in this study is in marked contrast to the degradation rates observed in earlier in vivo studies of pure molybdenum. In the studies of molybdenum wires implanted into the aortic walls of Wistar rats [36] or mice [27], degradation product layers of more than 10 \(\upmu\)m formed on the surfaces when the wires were integrated into the aortic wall. For the samples in the present study, the thickness of the degradation product layer was much lower than 1 \(\upmu\)m. The thickness of the degradation product layer is a good indication of the total amount of dissolved molybdenum in a sample. Molybdenum does not dissolve from the metallic state, but undergoes several oxidation steps along a reaction cascade, leading to soluble-form MoO\({}_{3}\) and, finally, dissolved-form Mo\({}_{4}\)\({}^{2-}\) (molybdate) [37]. The rate-limiting step is the reaction of Mo\({}_{2}\)O\({}_{5}\) (s) + H\({}_{2}\)O (I) \(\leftrightarrow\) Mo\({}_{2}\)O\({}_{5}\)OH (s) + H\({}^{+}\)[38] + e\({}^{-}\)[39].