In Vivo Degradation Behavior of the Magnesium Alloy LANd442 in Rabbit Tibiae

In former studies the magnesium alloy LAE442 showed promising in vivo degradation behavior and biocompatibility. However, reproducibility might be enhanced by replacement of the rare earth composition metal "E" by only a single rare earth element. Therefore, it was the aim of this study to examine whether the substitution of "E" by neodymium ("Nd") had an influence on the in vivo degradation rate. LANd442 implants were inserted into rabbit tibiae and rabbits were euthanized after 4, 8, 13 and 26 weeks postoperatively. In vivo μCT was performed to evaluate the in vivo implant degradation behaviour by calculation of implant volume, density true 3-D thickness and corrosion rates. Additionally, weight loss, type of corrosion and mechanical stability were appraised by SEM/EDS-analysis and three-point bending tests. Implant volume, density and true 3-D thickness decreased over time, whereas the variance of the maximum diameters within an implant as well as the corrosion rate and weight loss increased. SEM examination revealed mainly pitting corrosion after 26 weeks. The maximum bending forces decreased over time. In comparison to LAE442, the new alloy showed a slower, but more uneven degradation behavior and less mechanical stability. To summarize, LANd442 appeared suitable for low weight bearing bones but is inferior to LAE442 regarding its degradation morphology and strength

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 mu g/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)alpha. 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 TNF alpha 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

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

The current performance of biodegradable magnesium-based implants in magnetic resonance imaging: A review

Magnesium-based implants are re-emerging as a substantial amendment to standard orthopaedic implants. A brief introduction of magnesium (Mg) as a biodegradable material and basic magnetic resonance imaging (MRI) principles are discussed. This review aims to highlight the current performance of these implants during examinations with MRI. We also aim to summarise comparisons between Mg-based implants with current standards to emphasise the promotion of biodegradable implants in clinical practice. A comprehensive search of current literature on Mg-based implants and the utilisation of MRI in the studies was performed. Additionally, recorded artefact behaviour of Mg-based implants during MRI was investigated. A total of nine studies were included in which MRI was employed to image Mg-based implants. Of those studies, four of the nine discuss artefact production caused by the implants. MRI successfully imaged regions of interest over all and produced fewer artefacts than other materials used in the studies. MRI was employed in contrast angiography, bone growth observation, bone infection healing, and blood perfusion. Imaging capabilities of an implant material are vital to translating products into clinical application. Positive findings presented in this review suggest and support the use of Mg-based implants due to their successful visual compatibility with MRI techniques

The influence of storage and heat treatment on a magnesium-based implant material: An in vitro and in vivo study

© 2015 Bracht et al. Background: Magnesium alloys are recommended as a potential material for osteosynthesis. It is known that storage-induced property modifications can occur in materials like aluminum. Thus the aim of this study was to analyze the influence of storage durations of up to 48weeks on the biomechanical, structural, and degradation properties of the degradable magnesium alloy LAE442. Methods: Extruded implants (n=104; Ø 2.5mm×25mm) were investigated after storage periods of 0, 12, 24, and 48weeks in three different sub-studies: (I) immediately after the respective storage duration and after an additional (II) 56days of in vitro corrosion in simulated body fluid (SFB), and (III) 48weeks in vivo corrosion in a rabbit model, respectively. In addition, the influence of a T5-heat treatment (206°C for 15h in an argon atmosphere) was tested (n=26; 0week of storage). Evaluation was performed by three-point bending, scanning electron microscopy, radiography, μ-computed tomography, evaluation of the mean grain size, and contrast analysis of precipitations (such as aluminum or lithium). Results: The heat treatment induced a significant reduction in initial stability, and enhanced the corrosion resistance. In vivo experiments showed a good biocompatibility for all implants. During the storage of up to 48weeks, no significant changes occurred in the implant properties. Conclusions: LAE442 implants can be safely used after up to 48weeks of storage

Biodegradable Materials for Medical Applications II

To mitigate the long-term side effects associated with current corrosion-resistant implants, a new generation of bioabsorbable medical devices is currently being developed and have already been approved in some markets (e.g., Europe). Implants made of biodegradable materials are absorbed and excreted by the body after completing their temporary mechanical, scaffolding, and biointegration functions. Biochemical and mechanical attributes of all classes of materials, including metals, ceramics, and polymers, have been broadly explored by scientific and industrial research and development laboratories for various clinical applications over the last 2 decades. The second (biannual) international symposium Biodegradable Materials for Medical Applications took place during the TMS 2020 Annual Meeting in San Diego, CA and addressed the emerging multidisciplinary field of biodegradable materials and implants, involving materials scientists and engineers working with biologists, bioengineers, and medical personnel. The symposium had four oral sessions with 4 keynote presentations, 7 invited talks, and 18 regular presentations, and a poster session with 11 posters. Papers presented covered a broad range of topics related to materials selection, development, processing, and testing, material surface treatments, and modifications, in vitro/in vivo performance assessment, and evaluation of biodegradable-based implants, including vascular, orthopedic, tissue engineering, and other applications, presented by representatives from Canada, China, Germany, Hong Kong, Italy, Poland, Singapore, Slovenia, and the USA. Nearly two dozen selected quality papers were submitted for publication into three journals, including JOM (this issue), Metallurgical and Materials Transactions A (to be published in volume 51), and Surface Innovations (to be published in volume 8). Although the papers from the first symposium in this series were not published, last year, the April 2019 issue of JOM (vol. 71, no. 4) offered five papers on characterization of biodegradable medical materials. The papers can be downloaded from the journal website, with the table of contents page for this issue available at: http://link.springer.com/journal/11837/71/4/page/1

Biocompatibility of MgF \u3c inf\u3e 2 -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 180 days. 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 180 days. 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

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