Radiofrequency induced heating of biodegradable orthopaedic screw implants during magnetic resonance imaging.

Magnesium (Mg)-based implants have re-emerged in orthopaedic surgery as an alternative to permanent implants. Literature reveals little information on how the degradation of biodegradable implants may introduce safety implications for patient follow-up using medical imaging. Magnetic resonance imaging (MRI) benefits post-surgery monitoring of bone healing and implantation sites. Previous studies demonstrated radiofrequency (RF) heating of permanent implants caused by electromagnetic fields used in MRI. Our investigation is the first to report the effect of the degradation layer on RF-induced heating of biodegradable orthopaedic implants. WE43 orthopaedic compression screws underwent in vitro degradation. Imaging techniques were applied to assess the corrosion process and the material composition of the degraded screws. Temperature measurements were performed to quantify implant heating with respect to the degradation layer. For comparison, a commercial titanium implant screw was used. Strongest RF induced heating was observed for non-degraded WE43 screw samples. Implant heating had shown to decrease with the formation of the degradation layer. No statistical differences were observed for heating of the non-degraded WE43 material and the titanium equivalent. The highest risk of implant RF heating is most pronounced for Mg-based screws prior to degradation. Amendment to industry standards for MRI safety assessment is warranted to include biodegradable materials.

Evaluating metallic artefact of biodegradable magnesium-based implants in magnetic resonance imaging.

Magnesium (Mg) implants have shown to cause image artefacts or distortions in magnetic resonance imaging (MRI). Yet, there is a lack of information on how the degradation of Mg-based implants influences the image quality of MRI examinations. In this study, Mg-based implants are analysed in vitro, ex vivo, and in the clinical setting for various magnetic field strengths with the aim to quantify metallic artefact behaviour. In vitro corroded Mg-based screws and a titanium (Ti) equivalent were imaged according to the ASTM F2119. Mg-based and Ti pins were also implanted into rat femurs for different time points and scanned to provide insights on the influence of soft and hard tissue on metallic artefact. Additionally, MRI data of patients with scaphoid fractures treated with CE-approved Mg-based compression screws (MAGNEZIX®) were analysed at various time points post-surgery. The artefact production of the Mg-based material decreased as implant material degraded in all settings. The worst-case imaging scenario was determined to be when the imaging plane was selected to be perpendicular to the implant axis. Moreover, the Mg-based implant outperformed the Ti equivalent in all experiments by producing lower metallic artefact (p < 0.05). This investigation demonstrates that Mg-based implants generate significantly lower metallic distortion in MRI when compared to Ti. Our positive findings suggest and support further research into the application of Mg-based implants including post-operative care facilitated by MRI monitoring of degradation kinetics and bone/tissue healing processes.

Osteosynthesis of a cranio-osteoplasty with a biodegradable magnesium plate system in miniature pigs.

Biodegradable magnesium alloys are a new class of implant material suitable for bone surgery. The aim of this study was to investigate plates and screws made of magnesium for osteosynthesis in comparison to titanium in a cranial fracture model. Implants were used for internal fixation of a cranio-osteoplasty in nine minipigs. Computed tomography was conducted repeatedly after surgery. The implants and the adjacent tissues were harvested 10, 20 and 30weeks after surgery and investigated by micro-computed tomography and histological analysis. The surgical procedure and the inserted osteosynthesis material were well tolerated by the animals, and the bone healing of the osteoplasty was undisturbed at all times. The adjacent bone showed formation of lacunas in the magnesium group, resulting in a lower bone-to-implant contact ratio than that of titanium (72 vs. 94% at week 30), but this did not lead to clinical side effects. Radiological measurements showed no reduction in osteosynthesis material volume, but indicated signs of degradation: distinct volumes within the magnesium osteosynthesis group had lower density in micro-computed tomography, and these volumes increased up to 9% at week 30. The histological preparations showed areas of translucency and porosity inside the magnesium, but the outer shape of the osteosynthesis material remained unchanged. No fracture or loosening of the osteosynthesis devices appeared. Soft tissue probes confirmed sufficient biocompatibility. Given their biodegradable capacity, biocompatibility, mechanical strength and visibility on radiographs, osteosynthesis plates made of magnesium alloys are suitable for internal fixation procedures. STATEMENT OF SIGNIFICANCE: To the best of our knowledge this is the first study that used biodegradable magnesium implants for osteosynthesis in a cranial fracture model. The cranio-osteoplasty in miniature pigs allowed in vivo application of plate and screw osteosynthesis of standard-sized implants and the implementation of surgical procedures similar to those conducted on human beings. The osteosynthesis configuration, size, and mechanical properties of the magnesium implants within this study were comparable to those of titanium-based osteosynthesis materials. The results clearly show that bone healing was undisturbed in all cases and that the biocompatibility to hard- and soft tissue was sufficient. Magnesium implants might help to avoid long-term complications and secondary removal procedures due to their biodegradable properties.

Biodegradable nasal stents (MgF2 -coated Mg-2 wt %Nd alloy)-A long-term in vivo study.

Despite innovative surgical techniques and use of current frontal sinus stents from different materials, the problem of treatment failure with consecutive reoperation remains present. The aim of our study is to investigate biocompatibility, degradation kinetics, and functionality of a newly developed fluoride-coated magnesium-based nasal stent. A minipig anatomy of frontal sinus adapted design and an external surgical approach were developed and established. The functionality of the stents was evaluated endoscopically. The stent-tissue blocks were analysed after 90 and 180 days using microcomputed tomography (µ-CT), histology, scanning electron microscopy (SEM), and energy-dispersive X-ray spectroscopy (EDS). Functional evaluation revealed an unobstructed stent lumen in all cases. Histological analysis showed moderate mucosal hyperplasia with a mild, nonspecific inflammatory response, and nonosteoconductive effect. Rejection reactions or necrosis did not occur. The volumetric analysis of the stents showed 51% volume loss after 180 days. The EDS analysis did not detect any neodymium (Nd) in the mucosa or bone. The Mg-2 wt % Nd stents are a promising option when treating the narrow passages following paranasal sinus surgery. In particular, its good biocompatibility and good functionality facilitate the re-epithelization of these constricted passages. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 350-365, 2017.

Differential magnesium implant corrosion coat formation and contribution to bone bonding.

Magnesium alloys are presently under investigation as promising biodegradable implant materials with osteoconductive properties. To study the molecular mechanisms involved, the potential contribution of soluble magnesium corrosion products to the stimulation of osteoblastic cell differentiation was examined. However, no evidence for the stimulation of osteoblast differentiation could be obtained when cultured mesenchymal precursor cells were differentiated in the presence of metallic magnesium or in cell culture medium containing elevated magnesium ion levels. Similarly, in soft tissue no bone induction by metallic magnesium or by the corrosion product magnesium hydroxide could be observed in a mouse model. Motivated by the comparatively rapid accumulation solid corrosion products physicochemical processes were examined as an alternative mechanism to explain the stimulation of bone growth by magnesium-based implants. During exposure to physiological solutions a structured corrosion coat formed on magnesium whereby the elements calcium and phosphate were enriched in the outermost layer which could play a role in the established biocompatible behavior of magnesium implants. When magnesium pins were inserted into avital bones, corrosion lead to increases in the pull out force, suggesting that the expanding corrosion layer was interlocking with the surrounding bone. Since mechanical stress is a well-established inducer of bone growth, volume increases caused by the rapid accumulation of corrosion products and the resulting force development could be a key mechanism and provide an explanation for the observed stimulatory effects of magnesium-based implants in hard tissue. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 697-709, 2017.

Evaluation of the inflammatory potential of implant materials in a mouse model by bioluminescent imaging of intravenously injected bone marrow cells.

To evaluate the inflammatory potential of implants a bioluminescent imaging assay was developed using luciferase-expressing bone marrow cells that were injected into the blood circulation of wild-type mice. After subcutaneous implantation of titanium discs as an example for a clinically established biocompatible material, the luminosity was modest. Similarly, low luminosity signals were generated by pure magnesium implants that were used to represent metallic alloys that are presently under investigation as novel degradable implant materials. Increased luminosity was observed in response to degradable polymeric PLGA implants. Surgical wounds induced a basic luminescent response even in the absence of an implant. However, the material-independent response to injury could be minimized using injectable microparticle suspensions. In parallel with the resorption of biodegradable microparticles, the signal induced by PLGA declined faster when compared to non-degradable polystyrene suspensions. By using an interferon type I inducible Mx2 promoter construct to drive luciferase gene expression, the highest luminosity was observed in response to bacteria, indicating that the system could also be employed to monitor implant infections. Overall, labeled bone marrow cells yielded specific, well-defined localized signals that correlated with the inflammatory responses to implants. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 2149-2158, 2016.

Biocompatibility of MgF2-coated MgNd2 specimens in contact with mucosa of the nasal sinus - a long term study.

Up to now, different surgical techniques and stent systems have already been developed and tested for the continuous and adequate ventilation of the frontal sinuses. However, the results achieved still remain poor. Magnesium-based implants have been successfully used in numerous clinical applications. Offering excellent biocompatibility and biodegradability it may be the ideal material for the development of novel implants of the nasal sinus. Here, we present for the first time results on the behaviour of magnesium alloy in a unique environment, i.e. in contact to the nasal mucosa, air and nasal secretion. In a prospective longitudinal study, magnesium fluoride-coated MgNd2 specimens were implanted in the frontal sinuses of 12 minipigs for the investigation of biocompatibility and of the interface between the implant and the mucosa. Endoscopic examinations, histopathological evaluation and EDX measurements were performed regularly up to 180days. Endoscopic evaluation showed focal mucosal reaction, however, without affecting the patency of the sinus. In addition, no signs of bacterial infections were observed. The EDX analyses showed a marginal but steady increase in the Mg concentration in the mucosa over 180days. Histological analysis revealed a locally confined moderate mucosal hyperplasia and unspecific inflammatory reaction. Furthermore, we did not find any osteoinductive effects of the magnesium alloy. The results indicate the excellent biocompatibility of the MgNd2 alloy in contact with nasal mucosa and provide a novel material compound and solid proof-of-principle for the development of magnesium-based nasal stents.

Degradation behaviour of LAE442-based plate-screw-systems in an in vitro bone model.

The use of absorbable implant materials for fixation after bone fracture helps to avoid a second surgery for implant removal and the risks and costs involved. Magnesium (Mg) is well known as a potential metallic material for degradable implants. The aim of the present in vitro study was to evaluate if degradable LAE442-based magnesium plate-screw-systems are suitable candidates for osteosynthesis implants in load-bearing bones. The corrosion behaviour was tested concerning the influence of different surface treatments, coatings and screw torques. Steel plates and screws of the same size served as control. Plates without special treatment screwed on up to a specified torque of 15cNm or 7cNm, NaOH treated plates (15cNm), magnesium fluoride coated plates (15cNm) and steel plates as control (15cNm) were examined in pH-buffered, temperature-controlled SBF solution for two weeks. The experimental results indicate that the LAE442 plates and screws coated with magnesium fluoride revealed a lower hydrogen evolution in SBF solution as well as a lower weight loss and volume decrease in µ-computed tomography (µCT). The nanoindentation and SEM/EDX measurements at several plate areas showed no significant differences. Summarized, the different screw torques did not affect the corrosion behaviour differently. Also the NaOH treatment seemed to have no essential influence on the degradation kinetics. The plates coated with magnesium fluoride showed a decreased corrosion rate. Hence, it is recommended to consider this coating for the next in vivo study.

Magnesium corrosion particles do not interfere with the immune function of primary human and murine macrophages.

Magnesium is currently under investigation as a prospective biodegradable implant material. Biodegradation of magnesium causes a release of magnesium, hydroxide ions and hydrogen gas but it can also lead to the formation of particulate debris. Implant-derived particles may have immunotoxic effects. To investigate the influence of magnesium-derived particles on the immune functions of primary macrophages, up to 500 µg/ml magnesium or magnesium corrosion particles were added to the cell culture medium. No major effects were observed on cell viability and on the release of the proinflammatory cytokine tumor necrosis factor (TNF)α. In addition, the ability of macrophages to stimulate proliferation of allogenic lymphocytes in a mixed leukocyte reaction remained unaffected. When macrophages were incubated with magnesium particles and then infected with the apathogenic Mycobacterium smegmatis, infection-induced TNFα secretion from murine macrophages was inhibited but not from human macrophages. However, the bactericidal activity of either cell type was not influenced. In conclusion, magnesium-related particles did not restrict the immune function of macrophages, suggesting that magnesium implants and corrosion particles derived thereof are highly biocompatible and have a low inflammatory potential.

Evaluation of the biocompatibility of two magnesium alloys as degradable implant materials in comparison to titanium as non-resorbable material in the rabbit.

The aim of this study is to compare the biocompatibility of the two magnesium based alloys LAE442 and LANd442 with that of titanium. For this purpose, cylindrical implants were introduced into the medullary cavity of rabbit's tibiae for 4 and 8 weeks. Animals without any implant served as a control. In the follow-up, clinical, X-ray and µCT-investigations were performed to evaluate the reactions of the bone towards the implanted materials. After euthanasia, ex vivo µCT- and histological investigations were performed to verify the results of the in vivo tests. It could be shown that all materials induce changes in the bone. Whereas LANd442 caused the most pronounced reactions, such as increasing bone volume and bone porosity and decreasing bone density, titanium showed the most bone-implant contact by forming trabeculae. The tibiae of rabbits without implants also reacted by forming cavities, it is therefore assumed that the surgery method itself influences the bone.

Long-term in vivo degradation behaviour and biocompatibility of the magnesium alloy ZEK100 for use as a biodegradable bone implant.

Magnesium alloys are the focus of research as resorbable materials for osteosynthesis, as they provide sufficient stability and would make surgery to remove implants unnecessary. The new degradable magnesium alloy ZEK100 was developed to improve the stability and corrosion resistance by alloying with zinc, rare earth metals and zirconium. As the implants were degraded to only a limited extent after 6 months implantation in a previous in vivo study the present study was conducted to evaluate the long-term degradation behaviour and biocompatibility in the same animal model over 9 and 12 months. Five rabbits each with intramedullary tibia implants were examined over 9 and 12 months. Three legs were left without an implant to serve as negative controls. Numerous examinations were performed in the follow-up (clinical examinations, serum analysis, and radiographic and in vivo micro-CT investigations) and after death (ex vivo micro-CT, histology, and implant analysis) to assess the in vivo degradation and biocompatibility. It could be shown that favourable in vivo degradation behaviour is not necessarily associated with good biocompatibility. Although ZEK100 provided a very high initial stability and positive biodegradation, it must be excluded from further biomedical testing as it showed pathological effects on the host tissue following complete degradation.

In vivo assessment of the host reactions to the biodegradation of the two novel magnesium alloys ZEK100 and AX30 in an animal model.

BACKGROUND: Most studies on biodegradable magnesium implants published recently use magnesium-calcium-alloys or magnesium-aluminum-rare earth-alloys.However, since rare earths are a mixture of elements and their toxicity is unclear, a reduced content of rare earths is favorable. The present study assesses the in vivo biocompatibility of two new magnesium alloys which have a reduced content (ZEK100) or contain no rare earths at all (AX30). METHODS: 24 rabbits were randomized into 4 groups (AX30 or ZEK100, 3 or 6 months, respectively) and cylindrical pins were inserted in their tibiae. To assess the biodegradation µCT scans and histological examinations were performed. RESULTS: The µCT scans showed that until month three ZEK100 degrades faster than AX30, but this difference is leveled out after 6 months. Histology revealed that both materials induce adverse host reactions and high numbers of osteoclasts in the recipient bone. The mineral apposition rates of both materials groups were high. CONCLUSIONS: Both alloys display favorable degradation characteristics, but they induce adverse host reactions, namely an osteoclast-driven resorption of bone and a subsequent periosteal formation of new bone. Therefore, the biocompatibility of ZEK100 and AX30 is questionable and further studies, which should focus on the interactions on cellular level, are needed.

Ex vivo examination of the biocompatibility of biodegradable magnesium via microdialysis in the isolated perfused bovine udder model.

PURPOSE: Being biodegradable, magnesium is considered a promising future implant material but very little is known about the biocompatibility for the tissues in direct contact with it. In this study, the degradation of pure magnesium implants in the skin of an isolated bovine udder was examined over a period of five hours. METHODS: Microdialysis technique was used in order to investigate the reactions at the interface of implant and tissue. Pure titanium implants served as control. Degradation behavior and biocompatibility were evaluated via extracellular magnesium ion concentration and PGE2 and TNF alpha served as indicators of inflammation. RESULTS: Concentrations of 5.5 mmol/l Mg2+ were detected at the beginning, which decreased to a plateau of about 3.5 mmol/l after approximately two and a half hours. PGE2 and TNF alpha concentrations indicated no major inflammatory tissue response to the degradation. CONCLUSIONS: These results give an idea of the ion burden at the implantation site of degrading magnesium and suggest good biocompatibility even at the tissue-implant interface.