The biocompatibility and degradation behavior of pure molybdenum (Mo) as a bioresorbable metallic material (BMM) for implant applications were investigated. In vitro degradation of a commercially available Mo wire (ø250 µm) was examined after immersion in modified Kokubo’s SBF for 28 days at 37 °C and pH 7.4. For assessment of in vivo degradation, the Mo wire was implanted into the abdominal aorta of female Wistar rats for 3, 6 and 12 months. Microstructure and corrosion behavior were analyzed by means of SEM/EDX analysis. After explantation, Mo levels in serum, urine, aortic vessel wall and organs were investigated via ICP-OES analysis. Furthermore, histological analyses of the liver, kidneys, spleen, brain and lungs were performed, as well as blood count and differentiation by FACS analysis. Levels of the C-reactive protein were measured in blood plasma of all the animals. In vitro and in vivo degradation behavior was very similar, with formation of uniform, non-passivating and dissolving product layers without occurrence of a localized corrosion attack. The in vitro degradation rate was 101.6 µg/(cm2·d) which corresponds to 33.6 µm/y after 28 days. The in vivo degradation rates of 12, 33 and 36 µg/(cm2·d) were observed after 3, 6 and 12 months for the samples properly implanted in the aortic vessel wall. This corresponds with a degradation rate of 13.5 µm/y for the 12-month cohort. However, the magnitude of degradation strongly depended on the implant site, with the wires incorporated into the vessel wall showing the most severe degradation. Degradation of the implanted Mo wire neither induced an increase in serum or urine Mo levels nor were elevated Mo levels found in the liver and kidneys compared with the respective controls. Only in the direct vicinity of the implant in the aortic vessel wall, a significant amount of Mo was found, which, however, was far below the amounts to be expected from degrading wires. No abnormalities were detected for all timepoints in histological and blood analyses compared to the control group. The C-reactive protein levels were similar between all the groups, indicating no inflammation processes. These findings suggest that dissolved Mo from a degrading implant is physiologically transported and excreted. Furthermore, radiographic and µCT analyses revealed excellent radiopacity of Mo in tissues. These findings and the unique combination with its extraordinary mechanical properties make Mo an interesting alternative for established BMMs.
The degradation behavior and biocompatibility of pure molybdenum (Mo) were investigated. Dissolution of powder metallurgically manufactured and commercially available Mo was investigated by ion concentration measurement after immersion in modified Kokubo’s SBF (c-SBF-Ca) for 28 days at 37 °C and pH 7.4. Degradation layers and corrosion attack were examined with optical microscopy and REM/EDX analysis. Furthermore, potentiodynamic polarization measurements were conducted. Mo gradually dissolves in modified SBF releasing molybdate anions (MoO42−). The dissolution rate after 28 days is 10 µm/y for both materials and dissolution accelerates over time. A non-passivating, uniform and slowly soluble degradation product layer is observed. Additionally, apoptosis and necrosis assays with Mo ion extracts and colonization tests with human endothelial (HCAEC) and smooth muscle cell lines (HCASMC) on Mo substrates were performed. No adverse effects on cell viability were observed for concentrations expected from the dissolution of implants with typical geometries and substrates were densely colonized by both cell lines. Furthermore, Mo does not trigger thrombogenic or inflammatory responses. In combination with its favorable mechanical properties and the renal excretion of bio-available molybdate ions, Mo may be an alternative to established bioresorbable metals.
Titanium and stainless steel are commonly known as osteosynthesis materials with high strength and good biocompatibility. However, they have the big disadvantage that a second operation for hardware removal is necessary. Although resorbable systems made of polymers or magnesium are increasingly used, they show some severe adverse foreign body reactions or unsatisfying degradation behavior. Therefore, we started to investigate molybdenum as a potential new biodegradable material for osteosynthesis in craniomaxillofacial surgery. To characterize molybdenum as a biocompatible material, we performed in vitro assays in accordance with ISO Norm 10993-5. In four different experimental setups, we showed that pure molybdenum and molybdenum rhenium alloys do not lead to cytotoxicity in human and mouse fibroblasts. We also examined the degradation behavior of molybdenum by carrying out long-term immersion tests (up to 6 months) with molybdenum sheet metal. We showed that molybdenum has sufficient mechanical stability over at least 6 months for implants on the one hand and is subject to very uniform degradation on the other. The results of our experiments are very promising for the development of new resorbable osteosynthesis materials for craniomaxillofacial surgery based on molybdenum.
Titanium continues to be the gold standard in the field of osteosynthesis materials. This also applies to pediatric craniofacial surgery. Various resorbable materials have already been developed in order to avoid costly and risky second operations to remove metal in children. However, none of these resorbable materials have been able to completely replace the previous gold standard, titanium, in a satisfactory manner. This has led to the need for a new resorbable osteosynthesis material that fulfills the requirements for biocompatibility, stability, and uniform resorption. In our previous in vitro and in vivo work, we were able to show that molybdenum fulfills these requirements. To further confirm these results, we conducted a proof of concept in four domestic pigs, each of which was implanted with a resorbable molybdenum implant. The animals were then examined daily for local inflammatory parameters. After 54 days, the animals were euthanized with subsequent computer tomography imaging. We also removed the implants together with the surrounding tissue and parts of the spleen, liver, and kidney for histopathological evaluation. The molybdenum implants were also analyzed metallographically and using scanning electron microscopy. A blood sample was taken pre- and post-operatively. None of the animals showed clinical signs of inflammation over the entire test period. Histopathologically, good tissue compatibility was found. Early signs of degradation were observed after 54 days, which were not sufficient for major resorption. Resorption is expected with longer in situ residence times based on results of similar earlier investigations.