Influence of the grain size on the in vivo degradation behaviour of the magnesium alloy LAE442.

The aim of this study was to investigate the differences in the in vivo degradation behaviour of magnesium implants with various grain sizes and damaged surfaces. For this purpose, three different LAE442 magnesium implants were produced: cast, single and double extruded implants, in order to obtain different grain sizes. Furthermore, defects were positioned on the surfaces of some of the single extruded implants. The initial stability was determined. Four pins of each implant material were implanted into rabbits' tibiae and regularly clinically, radiologically and micro-computed tomographically investigated over a period of 27 weeks. Following explantation, investigations were carried out using stereo and scanning electron microscopy including energy-dispersive X-ray analyses. Weight and strength changes were measured. The double extruded implants possessing the finest grains exhibited the highest initial stability (179.18 N). These implants demonstrated the lowest in vivo corrosion rates (0.0134 mm/year) and the least radiologically visible changes. The highest corrosion rate was computed for the implants possessing damaged surfaces. Radiologically discernible bone changes occurred at almost the same time as implant changes for all groups. Based on these results, the aim should be to produce fine-grained magnesium-based alloys for resorbable implants and to avoid any surface damage.

The effects of handling and storage on magnesium based implants--first results.

The present work aimed to investigate the influence of acetone and formalin as well as the duration and type of storage on magnesium based implants by means of microscopic, µ-computed tomographic, scanning electron microscopic, EDX and metallographic investigations. In contrast to storing in acetone, storage in formalin led to an increase in surface to volume ratio, and a decrease of the volume and the density. The various types of storage exerted no differing effects on the implants but with increasing storage duration, a spreading of oxygen rich areas on the surface, increased precipitations and a decrease in grain size could be observed.

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.

Histological and molecular evaluation of iron as degradable medical implant material in a murine animal model.

A small animal model was established to evaluate the potential of iron as a degradable implant material. After insertion into the tail of mice, the implants gradually degraded over a clinically relevant time period of several months. Histological analysis and gene expression data from whole-genome microarray analyses indicated a limited inflammatory reaction. No evidence of cellular responses to excess iron ions was detected, suggesting that the iron degradation products were metabolically inactive. Iron-rich compounds could be detected in the vicinity of the implant and in individual cells distant from the implantation site. These results demonstrate that the mouse model could be useful for the primary in vivo evaluation of novel implant materials and that iron degradation products can accumulate in diverse organs of the body.

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.

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.

In Vivo Corrosion of Two Novel Magnesium Alloys ZEK100 and AX30 and Their Mechanical Suitability as Biodegradable Implants.

In magnesium alloys, the components used modify the alloy properties. For magnesium implants in contact with bone, rare earths alloys are commonly examined. These were shown to have a higher corrosion resistance than other alloys and a high mechanical strength, but their exact composition is hard to predict. Therefore a reduction of their content could be favorable. The alloys ZEK100 and AX30 have a reduced content or contain no rare earths at all. The aim of the study was to investigate their in vivo degradation and to assess the suitability of the in vivo µCT for the examination of their corrosion. Implants were inserted in rabbit tibiae. Clinical examinations, X-rays and in vivo µCT scans were done regularly. Afterwards implants were analyzed with REM, electron dispersive X-ray (EDX), weighing and mechanical testing. The in vivo µCT is of great advantage, because it allows a quantification of the corrosion rate and qualitative 3D assessment of the corrosion morphology. The location of the implant has a remarkable effect on the corrosion rate. Due to its mechanical characteristics and its corrosion behavior, ZEK100 was judged to be suitable, while AX30, which displays favorable degradation behavior, has too little mechanical strength for applications in weight bearing bones.

Biomechanical testing and degradation analysis of MgCa0.8 alloy screws: a comparative in vivo study in rabbits.

The aim of this study was to compare the biomechanical properties of degradable magnesium calcium alloy (MgCa0.8) screws and commonly used stainless steel (S316L) screws and to assess the in vivo degradation behavior of MgCa0.8. MgCa0.8 screws (n=48) and S316L screws (n=32) were implanted into both tibiae of 40 adult rabbits for a follow-up of 2, 4, 6 and 8 weeks. This resulted in a testing group of MgCa0.8 (n=12) and S316L (n=8) screws for each follow-up. Uniaxial pull-out tests were carried out in an MTS 858 Mini Bionix at a rate of 0.1 mm s(-1). For degradation analysis of MgCa0.8 in vivo micro-computed tomography (µCT) was performed to determine the volume of metal alloy remaining. Retrieved MgCa0.8 screws were analysed for degradation by determination of weight changes, scanning electron microscopy and energy dispersive X-ray analyses. No significant differences could be noted between the pull-out forces of MgCa0.8 and S316L 2 weeks after surgery (P=0.121). Six weeks after surgery the pull-out force of MgCa0.8 decreased slightly. In contrast, the S316L pull-out force increased with time. Thus, significantly higher pull-out values were detected for S316L from 4 weeks on (P<0.001). The volume and weight of MgCa0.8 gradually reduced. A corrosion layer, mainly composed of oxygen, magnesium, calcium and phosphorus, formed on the implants. Since MgCa0.8 showed good biocompatibility and biomechanical properties, comparable with those of S316L in the first 2-3 weeks of implantation, its application as a biodegradable implant is conceivable.

The effect of two point mutations in GDF-5 on ectopic bone formation in a beta-tricalciumphosphate scaffold.

The osteoinductivity of human growth-and-differentiation factor-5 (GDF-5) is well established, but a reduced amount of ectopic bone is formed compared to other members of the bone morphogenetic protein (BMP) family like BMP-2. We hypothesized that swap of two BMP-receptor-interacting residues of GDF-5 to amino acids present in BMP-2 (methionine to valine at the sites 453 and 456) may improve the bone formation capacity of the mutant GDF-5. Heterotopic bone formation of a mutant GDF-5 coated beta-TCP carrier was compared to carriers coated with similar amounts (10 microg) of GDF-5 and BMP-2 in SCID mice. Four week explants revealed 6-fold higher ALP activity in the mutant GDF-5 versus the wild type GDF-5 group (p < 0.0001) and 1.4-fold higher levels compared to BMP-2 (p < 0.006). Bone area in histology was significantly higher in mutant GDF-5 versus all other groups at 4 weeks; however, at 8 weeks BMP-2 reached a similar neo-bone formation like mutant GDF-5. Micro-CT evaluation confirmed higher values in the mutant GDF-5 and BMP-2 groups compared to wild type GDF-5. In conclusion, the mutant GDF-5 showed superior bone formation capacity than GDF-5, and a faster induction at similar final outcome as BMP-2. Mutant GDF-5 thus represents a promising new GDF-5 variant for bone regeneration possibly acting via an increased binding affinity to the BMP-type I receptor.

Influence of a magnesium-fluoride coating of magnesium-based implants (MgCa0.8) on degradation in a rabbit model.

MgCa0.8 cylinders (2.5 x 25 mm(2)) were coated with a magnesium-fluoride layer and implanted in the marrow cavities of both tibiae of 10 New Zealand White rabbits. The implantation duration was 3 and 6 months. The implants were clinically well tolerated. Micro-computed tomography revealed a new bone formation at the edges of the implants as well as an endosteal and periosteal remodeling. Using EDX-analysis, a calcium and phosphorus rich degradation layer could be found on the implant surface. It was covered by an incomplete layer containing fluoride. The analysis by weight before implantation and after 3 and 6 months, respectively, showed a slight decrease in volume in comparison to uncoated implants. When compared with uncoated implants, the mechanical properties of the coated implants exhibited a reduction in strength after 3 months. After 6 months, the strength of the coated implants was higher than that of uncoated cylinders.