Naoko Ikeo

Fabrication of a magnesium alloy with excellent ductility for biodegradable clips.

UNLABELLEDnTo develop a biodegradable clip, the equivalent plastic strain distribution during occlusion was evaluated by the finite element analysis (FEA) using the material data of pure Mg. Since the FEA suggested that a maximum plastic strain of 0.40 is required to allow the Mg clips, the alloying of magnesium with essential elements and the control of microstructure by hot extrusion and annealing were conducted. Mechanical characterization revealed that the Mg-Zn-Ca alloy obtained by double extrusion followed by annealing at 673K for 2h possessed a fracture strain over 0.40. The biocompatibility of the alloy was confirmed here by investigating its degradation behavior and the response of extraperitoneal tissue around the Mg-Zn-Ca alloy. Small gas cavity due to degradation was observed following implantation of the developed Mg-Zn-Ca clip by in vivo micro-CT. Histological analysis, minimal observed inflammation, and an only small decrease in the volume of the implanted Mg-Zn-Ca clip confirmed its excellent biocompatibility. FEA using the material data for ductile Mg-Zn-Ca also showed that the clip could occlude the simulated vessel without fracture. In addition, the Mg-Zn-Ca alloy clip successfully occluded the renal vein. Microstructural observations using electron backscattering diffraction confirmed that dynamic recovery occurred during the later stage of plastic deformation of the ductile Mg-Zn-Ca alloy. These results suggest that the developed Mg-Zn-Ca alloy is a suitable material for biodegradable clips.nnnSTATEMENT OF SIGNIFICANCEnSince conventional magnesium alloys have not exhibited significant ductility for applying the occlusion of vessels, the alloying of magnesium with essential elements and the control of microstructure by hot extrusion and annealing were conducted. Mechanical characterization revealed that the Mg-Zn-Ca alloy obtained by double extrusion followed by annealing at 673K for 2h possessed a fracture strain over 0.40. The biocompatibility of the alloy was confirmed by investigating its degradation behavior and the response of extraperitoneal tissue around the Mg-Zn-Ca alloy. Finite element analysis using the material data for the ductile Mg-Zn-Ca alloy also showed that the clip could occlude the simulated vessel without fracture. In addition, the Mg-Zn-Ca alloy clip successfully occluded the renal vein. Microstructural observations using electron backscattering diffraction confirmed that dynamic recovery occurred during the later stage of plastic deformation of the ductile Mg-Zn-Ca alloy.

In vivo corrosion behaviour of magnesium alloy in association with surrounding tissue response in rats

Biodegradable magnesium (Mg) alloys are the most promising candidates for osteosynthesis devices. However, their in vivo corrosion behaviour has not been fully elucidated. The aim of this study was to clarify the influence of the physiological environment surrounding Mg alloys on their corrosion behaviour. A Mg-1.0Al alloy with a fine-grained structure was formed into plates using titanium (Ti) as a control. These plates were implanted into the subperiosteum in the head, subcutaneous tissue of the back, and in the muscle of the femur of rats for 1, 2 and 4 weeks. The volumes of the remaining Mg alloy and of the insoluble salt deposition and gas cavities around the Mg alloy were determined by microtomography, and the volume losses were calculated. Then, the tissue response around the plates in each implantation site was examined histopathologically, and its relation to the respective volume loss was analyzed. These analyses determined that the Mg alloy was corroded fastest in the head, at an intermediate level in the back, and slowest in the femur. The insoluble salt deposition at the Mg alloy surface had no influence on the volume loss. Gas cavities formed around the Mg alloy at all implantation sites and decreased after 4 weeks. Histopathological examination revealed that the Mg alloy exhibited good biocompatibility, as was seen with Ti. In addition, vascularized fibrous capsules formed around the plates and became mature with time. Notably, the volume loss in the different anatomical locations correlated with capsule thickness. Together, our results suggest that, to facilitate the successful clinical application of Mg alloys, it will be necessary to further comprehend their interactions with specific in vivo environments.

Development of a new biodegradable operative clip made of a magnesium alloy: Evaluation of its safety and tolerability for canine cholecystectomy

Background: Operative clips used to ligate vessels in abdominal operation usually are made of titanium. They remain in the body permanently and form metallic artifacts in computed tomography images, which impair accurate diagnosis. Although biodegradable magnesium instruments have been developed in other fields, the physical properties necessary for operative clips differ from those of other instruments. We developed a biodegradable magnesium‐zinc‐calcium alloy clip with good biologic compatibility and enough clamping capability as an operative clip. In this study, we verified the safety and tolerability of this clip for use in canine cholecystectomy. Methods: Nine female beagles were used. We performed cholecystectomy and ligated the cystic duct by magnesium alloy or titanium clips. The chronologic change of clips and artifact formation were compared at 1, 4, 12, 18, and 24 weeks postoperative by computed tomography. The animals were killed at the end of the observation period, and the clips were removed to evaluate their biodegradability. We also evaluated their effect on the living body by blood biochemistry data. Results: The magnesium alloy clip formed much fewer artifacts than the titanium clip, and it was almost absorbed at 6 months postoperative. There were no postoperative complications and no elevation of constituent elements such as magnesium, calcium, and zinc during the observation period in both groups. Conclusion: The novel magnesium alloy clip demonstrated sufficient sealing capability for the cystic duct and proper biodegradability in canine models. The magnesium alloy clip revealed much fewer metallic artifacts in CT than the conventional titanium clip.

Degradation Behavior of Mg-Ca Nail after Penetration into Artificial Bone

For applying a magnesium alloy to nails in the guided bone regeneration (GBR) method, sufficient strength and appropriate degradation speed are required to fix a membrane. In the case, the nails are exposed to body fluid after penetrating the alveolar bone. Therefore, in this research, degradation behavior after penetration of magnesium-calcium alloy which is expected to possess high biocompatibility was investigated. As a result, the Mg-Ca alloy nails were degraded inhomogeneously after immersion for 4 weeks in simulated body fluid. The degraded portions corresponded to the distribution of residual strain estimated by finite element analysis. Mg-Ca nails without precipitates possessed comparatively gradual degradation rate. It can be also confirmed that the region with residual strain degraded preferentially when compared the CT images and the residual strain distribution after penetration.

In vitro and in vivo analysis of the biodegradable behavior of a magnesium alloy for biomedical applications

The present study was designed to investigate the biodegradation behavior of Mg alloy plates in the maxillofacial region. For in vitro analysis, the plates were immersed in saline solution and simulated body fluid. For in vivo, the plates were implanted into the tibia, head, back, abdominal cavity, and femur and assessed at 1, 2, and 4 weeks after implantation. After implantation, the plate volumes and the formed insoluble salt were measured via micro-computed tomography. SEM/EDX analysis of the insoluble salt and histological analysis of the surrounding tissues were performed. The volume loss of plates in the in vitro groups was higher than that in the in vivo groups. The volume loss was fastest in the abdomen, followed by the head, back, tibia, and femur. There were no statistically significant differences in the insoluble salt volume of the all implanted sites. The corrosion of the Mg alloy will be affected to the surrounding tissue responses. The material for the plate should be selected based on the characteristic that Mg alloys are decomposed relatively easily in the maxillofacial region.

Evaluation of In Vitro Fatigue Properties of Biodegradable Mg–0.3at.%Ca Alloy

Recently, biodegradable bone fixation devices have been demanded when considering the patient’s quality of life (QOL). During the fracture healing, the devices must support the repeated load due to daily performance. At the same time, surface of the magnesium devices was affected by body fluid. Thus in this research, in vitro fatigue properties of biodegradable Mg–0.3at.%Ca alloy was evaluated by using simulated body fluid. Though there was fatigue limit when the test was conducted under the ambient condition, it cannot be confirmed during the test in the simulated body fluid. Inspection of fracture surface revealed that crack propagated along the grain boundary after both the fatigue tests.

Lattice Ordering and Microstructure of Ultra-high Strength Mg-Ca-Zn Alloys

Magnesium alloying with calcium is very promising for mechanical strength. One of the promising alloys systems is ternary Mg-Zn-Ca. Recent results by the first principles calculation suggest that the combination of calcium and zinc possibly enhances the cohesive energy of grain boundary. In this work, Mg-Zn-Ca alloys with low alloying amounts of 0.1–0.3at% Ca and 0.2–0.6at% Zn were studied. Very fine grain size of smaller than 0.5 micron was achieved after extrusion, with finer substructure of the order of 100 nm. Microstructure showed sharp grain boundaries A possible ordering of atoms in the matrix was observed. These ultra-fine and complex grain structures have been studied with the aid of advanced transmission electron microscopy techniques.

Superplastic Deformation Behavior in Dual-Phase Mg-Ca Alloy

Superplastic deformation behavior was investigated for a dual-phase Mg-Ca alloy. The elongation-to-failure reached more than 120% with the strain rate sensitivity, m, over 0.4. The activation energy required for the deformation was estimated to be 98 kJ/mol which is close to the activation energy for grain boundary diffusion in magnesium. Therefore, the superplastic deformation mechanism was suggested to be the grain boundary sliding rate, which is controlled by boundary diffusion.

Effect of Solute Segregation on Fracture Behavior of Mg Alloy

Improving mechanical properties of magnesium and understanding fracture behavior under impact loading are necessary to apply magnesium alloys to structural components of automobiles. We have investigated the fracture behavior of binary magnesium alloys by three-point bending experiment and conducted a first principle calculation to estimate the effect of solute segregation on fracture energy. In this paper, we have focused on experimental result of impact three-point bending test for Mg-0.3at.%Y alloy and the results of the test were compared with that of AZ31 commercially available alloy [1]. As a result, the crack propagation speed of Mg-0.3at.%Y was found to be slower than that of AZ31 alloys. Moreover, the absorbed energy of Mg-0.3at.%Y was more than twice as high as that of AZ31 alloys. These results suggested that yttrium solute in magnesium improved the fracture toughness of magnesium under impact loading. Then, fracture surface was observed by SEM to consider the effect of microstructure on crack propagation speed.