A bi-phase core-shell structure of Mg-based bulk metallic glass for application in orthopedic fixation implants.

Mg-based bulk metallic glass (BMG) and its composites have been promising candidates for orthopedic fixation implants because of their biocompatibility, low degradation rate, and osteogenic potential. However, the amorphous state is affected by the cooling rate during the casting process. Solid, unstable structures combined with amorphous and crystalline structures are generated when an insufficient cooling rate is used. Here, we aimed to design and synthesize a novel core-shell structure comprising an amorphous shell and a crystalline core in order to overcome the material size limit imposed by the cooling rate effects. Our results show that the core-shell structure of Mg-based BMG does have a lower degradation rate and can maintain a more amorphous structure after six weeks of degradation. Moreover, the biocompatibility and osteogenic effects were similar between the core-shell and solid structures of Mg-based BMG. In conclusion, the core-shell structure of Mg-based BMG exhibits a lower degradation rate while still enhancing osteogenic potential in vitro. This core-shell structure of Mg-based BMG overcomes the cooling rate effects and provides a new structure for manufacturing Mg-based BMG.

In-vivo investigations and cytotoxicity tests on Ti/Zr-based metallic glasses with various Cu contents.

The Ti/Zr-based metallic glasses (MGs) with various Cu contents are prepared, with nominal compositions of Ti45Zr40Si15 (Cu-free), Ti45Zr40Si10Cu5 (low-Cu), and Ti45Zr20Cu35 (high-Cu). The mechanical properties, corrosion resistance, and in-vitro biocompatibility of these MGs are investigated by means of nano-indentation, electrochemical analyses, MTS assays and inductively coupled plasma mass spectrometry, as well as in-vivo biocompatibility in terms of scanning electron microscopy, micro-CT scans and histological observations. The results show that the electrochemical activity and biocompatibility of the MGs are sensitive to the Cu content. Following the electrocorrosion tests, an increase in ion concentration is observed in high-Cu MG. Eight independent in-vitro tests show that the higher ion concentration leads to a lower cell viability. The twelve-week in-vivo tests show that the Cu-free MGs can be a promising material for developing bio-implants. The high-Cu MG would release Ti and Zr ions with insignificant Cu ion following corrosion testing, enhancing an increased local osteoclast activity.

Biocompatibility study on Ni-free Ti-based and Zr-based bulk metallic glasses.

Safety and reliability are crucial issues for medical instruments and implants. In the past few decays, bulk metallic glasses (BMGs) have drawn attentions due to their superior mechanical properties, good corrosion resistance, antibacterial and good biocompatibility. However, most Zr-based and Ti-based BMGs contain Ni as an important element which is prone to human allergy problem. In this study, the Ni-free Ti-based and Zr-based BMGs, Ti40Zr10Cu36Pd14, and Zr48Cu36Al8Ag8, were selected for systematical evaluation of their biocompatibility. Several biocompatibility tests, co-cultural with L929 murine fibroblast cell line, were carried out on these two BMGs, as well as the comparison samples of Ti6Al4V and pure Cu. The results in terms of cellular adhesion, cytotoxicity, and metallic ion release affection reveal that the Ti40Zr10Cu36Pd14 BMG and Ti6Al4V exhibit the optimum biocompatibility; cells still being attached on the petri dish with good adhesion and exhibiting the spindle shape after direct contact test. Furthermore, the Ti40Zr10Cu36Pd14 BMG showed very low Cu ion release level, in agreement with the MTT results. Based on the current findings, it is believed that Ni-free Ti-based BMG can act as an ideal candidate for medical implant.

Effects of Cu content on electrochemical response in Ti-based metallic glasses under simulated body fluid.

Systematic characterization of the corrosion response of the Cu-free Ti45Zr40Si15 and Cu-containing Ti40Zr40Si15-Cu5 and Ti45Zr20-Cu35 metallic glasses (MGs) in the Hank's solution is conducted, in terms of the open circuit potential, potentiodynamic polarization, as well as electrochemical impedance measurements. The Cu role in the Ti-based MGs, tentatively to be applied for bio-implants, is established and modeled. The presence of nobler Cu will impose two opposite effects. The minor positive effect of minor shift of Ecorr is not a major issue, but the negative effect on local pitting and ion release would cause a major drawback. The ICP-MS indicates that the release of Cu ions increases with increasing Cu content. For more promising anti-pitting ability, the Cu content in Ti-based MGs should be kept as low as possible, better to be none or less than about 5 at.%.

Electrochemical and biocompatibility response of newly developed TiZr-based metallic glasses.

This paper presents systematical investigations, including electrochemical activity, MTT cell assay and in vivo test, on the biocompatibility of three metallic glasses. The electrochemical behaviors and the cell toxicity of two newly developed TiZr-based metallic glasses (MGs), Ti42Zr40Si15Ta3 and Ti40Zr40Si15Cu5, with lower or without unfavorable elements are systematically investigated. Results show that the MGs with low Cu content exhibit a low electrochemical response. Cytotoxicity tests for the MGs and the mediums after the potential state test are evaluated with in vitro MTT assays. The solid specimens and the mediums after the potential state test for the pure Ti, Ti42Zr40Si15Ta3 and Ti40Zr40Si15Cu5 exhibit no significant cytotoxicity in the MTT test, while the tested medium for Ti45Cu35Zr20 MG shows lower cell viability. The inductively coupled plasma-mass spectrometry (ICP-MS) results also indicate that the Cu-rich sample released a significant amount of ions which may be the major factor causing the low viability in the MTT test. The good healing condition and the low C-reactive protein (CRP) index for the implanted New Zealand rabbits in a one-month in vivo test also show the satisfactory short-term biocompatibility of the TiZr-based MGs. The electrochemical measurements, in vitro, and in vivo experiments confirm that the developed TiZr-based MGs with lower Cu content (≦5%) are promising for biomedical purposes.

Rapid screening of potential metallic glasses for biomedical applications.

This paper presents a rapid screening process to select potential titanium and zirconium based metallic glasses (MGs) for bio-material applications. Electrochemical activity of 7 MGs including 6 bulk metallic glasses and 1 thin-film deposited MG in simulation body and human serum is first inspected. A low-voltage potential state test is also developed to simulate the cell membrane potential that the implant MGs will suffer. Results show that the MGs composed of Ti65Si15Ta10Zr10 and Ta57Zr23Cu12Ti8 exhibit excellent electrochemical stability in both simulation body fluid and human serum. In addition, the copper content in the MGs plays an important role on the electrochemical activity. MGs with the copper content higher than 17.5% show significant electrochemical responses. The cytotoxicity of the solid MG samples and the corrosion released ions are also evaluated by an in-vitro MTT test utilizing the murine bone marrow stem cells. Results indicate that all the solid MG samples show no acute cytotoxicity yet the corrosion released ions show significant toxicity for murine bone marrow stem cells. The rapid screening process developed in the present study suggests that the Ti65Si15Ta10Zr10 metallic glass has high potential for biomedical applications due to its good electrochemical stability and very low cytotoxicity.

Simulated body fluid electrochemical response of Zr-based metallic glasses with different degrees of crystallization.

The bio-electrochemical response in simulated body fluid of the Zr53Cu30Ni9Al8 metallic glasses with different degrees of partial crystallization was systematically examined and discussed. Through thermal annealing, the volume fractions of the crystalline phases are determined to be 0, 34, 63, and near 100%. Based on the bio-corrosion voltage and current, as well as the polarization resistance, it is concluded that the fully amorphous alloy exhibits the highest bio-electrochemical resistance. With an increasing degree of partial crystallization, the corrosion resistance becomes progressively degraded. The passive current reveals that the fully amorphous metallic glasses can form a more protective and denser passive film on the metallic glass surface. The formation of reactive nanocrystalline phases in the amorphous matrix would reduce the bio-corrosion resistance.

Inflammation-induced up-regulation of ionotropic glutamate receptor expression in human skin.

BACKGROUND: N-methyl-D-aspartate (NMDA), alpha-amino-3-hydroxy-5-methylisoxazolone-4-propionic acid (AMPA), and kainate (KA) receptors are members of the ionotropic glutamate receptor (iGluR) family and are increased in inflamed rat skin. These receptors contribute to inflammatory pain. In this study, we have examined whether there is a similar increase in iGluRs in inflamed human skin in the presence of inflammatory pain. METHODS: Normal and inflamed-skin biopsies were obtained from eight patients undergoing elective wound-debridement surgery. Real-time-polymerase chain reaction (PCR) and western blot analysis were used for quantitation of iGluR mRNA and protein in normal and inflamed human skin. RESULTS: A significant increase in mRNA and protein for NMDA, AMPA, and KA receptor subunits was detected in inflamed compared with normal skin. The amounts of NMDA (NR1 subunit), AMPA (GluR2 subunit), and KA (GluR6 subunit) mRNA in inflamed skin were mean 6 (SD 1.6-fold), 2.5 (0.6-fold), and 3.8 (0.9-fold) (P<0.05), respectively, greater than that measured in normal skin. The ratio of NR1, GluR2, and GluR6 protein in inflamed compared with normal skin was 5.7 (1.2), 2.4 (0.5), and 3.6 (0.9) (P<0.05), respectively. CONCLUSIONS: These results, in human tissue, demonstrate that iGluR mRNA and protein expression are increased during persistent inflammation and that this increased activity may be involved in mediating clinical inflammatory pain in human skin.