Detailing the influence of PEO-coated biodegradable Mg-based implants on the lacuno-canalicular network in sheep bone: A pilot study.

An increasing prevalence of bone-related injuries and aging geriatric populations continue to drive the orthopaedic implant market. A hierarchical analysis of bone remodelling after material implantation is necessary to better understand the relationship between implant and bone. Osteocytes, which are housed and communicate through the lacuno-canalicular network (LCN), are integral to bone health and remodelling processes. Therefore, it is essential to examine the framework of the LCN in response to implant materials or surface treatments. Biodegradable materials offer an alternative solution to permanent implants, which may require revision or removal surgeries. Magnesium alloys have resurfaced as promising materials due to their bone-like properties and safe degradation in vivo. To further tailor their degradation capabilities, surface treatments such as plasma electrolytic oxidation (PEO) have demonstrated to slow degradation. For the first time, the influence of a biodegradable material on the LCN is investigated by means of non-destructive 3D imaging. In this pilot study, we hypothesize noticeable variations in the LCN caused by altered chemical stimuli introduced by the PEO-coating. Utilising synchrotron-based transmission X-ray microscopy, we have characterised morphological LCN differences around uncoated and PEO-coated WE43 screws implanted into sheep bone. Bone specimens were explanted after 4, 8, and 12 weeks and regions near the implant surface were prepared for imaging. Findings from this investigation indicate that the slower degradation of PEO-coated WE43 induces healthier lacunar shapes within the LCN. However, the stimuli perceived by the uncoated material with higher degradation rates induces a greater connected LCN better prepared for bone disturbance.

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.

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.

Evaluation of wrought Zn-Al alloys (1, 3, and 5 wt % Al) through mechanical and in vivo testing for stent applications.

Special high grade zinc and wrought zinc-aluminum (Zn-Al) alloys containing up to 5.5 wt % Al were processed, characterized, and implanted in rats in search of a new family of alloys with possible applications as bioabsorbable endovascular stents. These materials retained roll-induced texture with an anisotropic distribution of the second-phase Al precipitates following hot-rolling, and changes in lattice parameters were observed with respect to Al content. Mechanical properties for the alloys fell roughly in line with strength (190-240 MPa yield strength; 220-300 MPa ultimate tensile strength) and elongation (15-30%) benchmarks, and favorable elastic ranges (0.19-0.27%) were observed. Intergranular corrosion was observed during residence of Zn-Al alloys in the murine aorta, suggesting a different corrosion mechanism than that of pure zinc. This mode of failure needs to be avoided for stent applications because the intergranular corrosion caused cracking and fragmentation of the implants, although the composition of corrosion products was roughly identical between non- and Al-containing materials. In spite of differences in corrosion mechanisms, the cross-sectional reduction of metals in murine aorta was nearly identical at 30-40% and 40-50% after 4.5 and 6 months, respectively, for pure Zn and Zn-Al alloys. Histopathological analysis and evaluation of arterial tissue compatibility around Zn-Al alloys failed to identify areas of necrosis, though both chronic and acute inflammatory indications were present. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 245-258, 2018.

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.

Phosphate conversion coating reduces the degradation rate and suppresses side effects of metallic magnesium implants in an animal model.

Magnesium alloys have promising mechanical and biological properties for the development of degradable implants. However, rapid implant corrosion and gas accumulations in tissue impede clinical applications. With time, the implant degradation rate is reduced by a highly biocompatible, phosphate-containing corrosion layer. To circumvent initial side effects after implantation it was attempted to develop a simple in vitro procedure to generate a similarly protective phosphate corrosion layer. To this end magnesium samples were pre-incubated in phosphate solutions. The resulting coating was well adherent during routine handling procedures. It completely suppressed the initial burst of corrosion and it reduced the average in vitro magnesium degradation rate over 56 days almost two-fold. In a small animal model phosphate coatings on magnesium implants were highly biocompatible and abrogated the appearance of gas cavities in the tissue. After implantation, the phosphate coating was replaced by a layer with an elemental composition that was highly similar to the corrosion layer that had formed on plain magnesium implants. The data demonstrate that a simple pre-treatment could improve clinically relevant properties of magnesium-based implants. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 1622-1635, 2017.

Magnesium alloys: A stony pathway from intensive research to clinical reality. Different test methods and approval-related considerations.

The first degradable implant made of a magnesium alloy, a compression screw, was launched to the clinical market in March 2013. Many different complex considerations are required for the marketing authorization of degradable implant materials. This review gives an overview of existing and proposed standards for implant testing for marketing approval. Furthermore, different common in vitro and in vivo testing methods are discussed. In some cases, animal tests are inevitable to investigate the biological safety of a novel medical material. The choice of an appropriate animal model is as important as subsequent histological examination. Furthermore, this review focuses on the results of various mechanical tests to investigate the stability of implants for temporary use. All the above aspects are examined in the context of development and testing of magnesium-based biomaterials and their progress them from bench to bedside. A brief history of the first market launch of a magnesium-based degradable implant is given. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 329-347, 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.

Susceptibility of metallic magnesium implants to bacterial biofilm infections.

Magnesium alloys have promising mechanical and biological properties as biodegradable medical implant materials for temporary applications during bone healing or as vascular stents. Whereas conventional implants are prone to colonization by treatment resistant microbial biofilms in which bacteria are embedded in a protective matrix, magnesium alloys have been reported to act antibacterial in vitro. To permit a basic assessment of antibacterial properties of implant materials in vivo an economic but robust animal model was established. Subcutaneous magnesium implants were inoculated with bacteria in a mouse model. Contrary to the expectations, bacterial activity was enhanced and prolonged in the presence of magnesium implants. Systemic antibiotic treatments were remarkably ineffective, which is a typical property of bacterial biofilms. Biofilm formation was further supported by electron microscopic analyses that revealed highly dense bacterial populations and evidence for the presence of extracellular matrix material. Bacterial agglomerates could be detected not only on the implant surface but also at a limited distance in the peri-implant tissue. Therefore, precautions may be necessary to minimize risks of metallic magnesium-containing implants in prospective clinical applications. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 1489-1499, 2016.

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

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 48 weeks on the biomechanical, structural, and degradation properties of the degradable magnesium alloy LAE442. METHODS: Extruded implants (n = 104; Ø 2.5 mm × 25 mm) were investigated after storage periods of 0, 12, 24, and 48 weeks in three different sub-studies: (I) immediately after the respective storage duration and after an additional (II) 56 days of in vitro corrosion in simulated body fluid (SFB), and (III) 48 weeks in vivo corrosion in a rabbit model, respectively. In addition, the influence of a T5-heat treatment (206 °C for 15 h in an argon atmosphere) was tested (n = 26; 0 week 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 48 weeks, no significant changes occurred in the implant properties. CONCLUSIONS: LAE442 implants can be safely used after up to 48 weeks of storage.

Metallic zinc exhibits optimal biocompatibility for bioabsorbable endovascular stents.

Although corrosion resistant bare metal stents are considered generally effective, their permanent presence in a diseased artery is an increasingly recognized limitation due to the potential for long-term complications. We previously reported that metallic zinc exhibited an ideal biocorrosion rate within murine aortas, thus raising the possibility of zinc as a candidate base material for endovascular stenting applications. This study was undertaken to further assess the arterial biocompatibility of metallic zinc. Metallic zinc wires were punctured and advanced into the rat abdominal aorta lumen for up to 6.5months. This study demonstrated that metallic zinc did not provoke responses that often contribute to restenosis. Low cell densities and neointimal tissue thickness, along with tissue regeneration within the corroding implant, point to optimal biocompatibility of corroding zinc. Furthermore, the lack of progression in neointimal tissue thickness over 6.5months or the presence of smooth muscle cells near the zinc implant suggest that the products of zinc corrosion may suppress the activities of inflammatory and smooth muscle cells.

Recent advances in biodegradable metals for medical sutures: a critical review.

Sutures that biodegrade and dissolve over a period of several weeks are in great demand to stitch wounds and surgical incisions. These new materials are receiving increased acceptance across surgical procedures whenever permanent sutures and long-term care are not needed. Unfortunately, both inflammatory responses and adverse local tissue reactions in the close-to-stitching environment are often reported for biodegradable polymeric sutures currently used by the medical community. While bioabsorbable metals are predominantly investigated and tested for vascular stent or osteosynthesis applications, they also appear to possess adequate bio-compatibility, mechanical properties, and corrosion stability to replace biodegradable polymeric sutures. In this Review, biodegradable alloys made of iron, magnesium, and zinc are critically evaluated as potential materials for the manufacturing of soft and hard tissue sutures. In the case of soft tissue closing and stitching, these metals have to compete against currently available degradable polymers. In the case of hard tissue closing and stitching, biodegradable sternal wires could replace the permanent sutures made of stainless steel or titanium alloys. This Review discusses the specific materials and degradation properties required by all suture materials, summarizes current suture testing protocols and provides a well-grounded direction for the potential future development of biodegradable metal based sutures.

In vivo evaluation of a magnesium-based degradable intramedullary nailing system in a sheep model.

The biocompatibility and the degradation behavior of the LAE442 magnesium-based intramedullary interlocked nailing system (IM-NS) was assessed in vivo in a comparative study (stainless austenitic steel 1.4441LA) for the first time. IM-NS was implanted into the right tibia (24-week investigation period; nails/screws diameter: 9 mm/3.5 mm, length: 130 mm/15-40 mm) of 10 adult sheep (LAE442, stainless steel, n=5 each group). Clinical and radiographic examinations, in vivo computed tomography (CT), ex vivo micro-computed tomography (µCT), mechanical and histological examinations and element analyses of alloying elements in inner organs were performed. The mechanical examinations (four-point bending) revealed a significant decrease of LAE442 implant stiffness, force at 0.2% offset yield point and maximum force. Periosteal (new bone formation) and endosteal (bone decline) located bone alterations occurred in both groups (LAE442 alloy more pronounced). Moderate gas formation was observed within the LAE442 alloy group. The CT-measured implant volume decreased slightly (not significant). Histologically a predominantly direct bone-to-implant interface existed within the LAE442 alloy group. Formation of a fibrous tissue capsule around the nail occurred in the steel group. Minor inflammatory infiltration was observed in the LAE442 alloy group. Significantly increased quantities of rare earth elements were detected in the LAE442 alloy group. µCT examination showed the beginning of corrosion in dependence of the surrounding tissue. After 24 weeks the local biocompatibility of LAE442 can be considered as suitable for a degradable implant material. STATEMENT OF SIGNIFICANCE: An application oriented interlocked intramedullary nailing system in a comparative study (degradable magnesium-based LAE442 alloy vs. steel alloy) was examined in a sheep model for the first time. We focused in particular on the examination of implant degradation by means of (µ-)CT, mechanical properties (four-point bending), clinical compatibility, local bone reactions (X-ray and histology) and possible systemic toxicity (histology and element analyses of inner organs). A significant decrease of magnesium (LAE442 alloy) implant stiffness and maximum force occurred. Moderate not clinically relevant gas accumulation was determined. A predominantly direct bone-to-implant contact existed within the magnesium (LAE442 alloy) group compared to an indirect contact in the steel group. Rare earth element accumulation could be observed in inner organs but H&E staining was inconspicuous.

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.