Short- and long-term exposure to trace metal(loid)s from the production of ferromanganese alloys by personal sampling and biomarkers.

The environmental exposure to trace metal(loid)s (As, Cd, Cu, Fe, Mn, Pb, and Zn) was assessed near a ferromanganese alloy plant using filters from personal particulate matter (PM) samplers (bioaccessible and non-bioaccessible fine and coarse fractions) and whole blood as short-term exposure markers, and scalp hair and fingernails as long-term biomarkers, collected from volunteers (n = 130) living in Santander Bay (northern Spain). Bioaccessible and non-bioaccessible metal(loid) concentrations in coarse and fine PM from personal samplers were determined by ICP-MS after extraction/digestion. Metal(loid) concentration in biomarkers was measured after alkaline dilution (whole blood) and acid digestion (fingernails and scalp hair) by ICP-MS as well. Results were discussed in terms of exposure, considering the distance to the main Mn source, and sex. In terms of exposure, significant differences were found for Mn in all the studied fractions of PM, As in whole blood, Mn and Cu in scalp hair and Mn and Pb in fingernails, with all concentrations being higher for those living closer to the Mn source, with the exception of Cu in scalp hair. Furthermore, the analysis of the correlation between Mn levels in the studied biomarkers and the wind-weighted distance to the main source of Mn allows us to conclude that scalp hair and mainly fingernails are appropriate biomarkers of long-term airborne Mn exposure. This was also confirmed by the significant positive correlations between scalp hair Mn and bioaccessible Mn in coarse and fine fractions, and between fingernails Mn and all PM fractions. This implies that people living closer to a ferromanganese alloy plant are exposed to higher levels of airborne metal(loid)s, mainly Mn, leading to higher levels of this metal in scalp hair and fingernails, which according to the literature, might affect some neurological outcomes. According to sex, significant differences were observed for Fe, Cu and Pb in whole blood, with higher concentrations of Fe and Pb in males, and higher levels of Cu in females; and for Mn, Cu, Zn, Cd and Pb in scalp hair, with higher concentrations in males for all metal(loid)s except Cu.

Method to Eliminate Fluoride Interference in the Spectrophotometric Estimation of Zirconium: Application to U-Zr Alloys.

In the estimation of Zr using the ultraviolet-visible (UV-Vis) spectrophotometric technique, fluoride interference is a decade-old unsolved problem. The process of repeated fuming with strong acids is often used to remove fluoride from the solution in order to estimate Zr using spectrophotometry analysis. For the first time, in this work, a simple use of AlCl3 is reported as a suppressing reagent to eliminate the interference of fluoride in the estimation of Zr. Xylenol orange in HCl medium is used as a complexing reagent. Linearity in the datum acquired from absorbance at 551 nm (λmax) is achieved over the concentration range 0.25-4.5 µg mL-1 of Zr with a molar absorptivity of 35030 L·mol-1·cm-1 and Sandell's sensitivity of 0.003 µg·cm-2. Zr is quantified in the variety of U-Zr alloys and various water samples using spectrophotometric detection with a classical univariate calibration with suppressing of fluoride interference through AlCl3. Results from this novel analytical method herein developed for the first time are compared with those achieved from gravimetric analysis.

The environmental geochemical baseline, background and sources of metal and metalloids present in urban, peri-urban and rural soils in the O´Higgins region, Chile.

The importance of environmental geochemistry baseline in soils of O´Higgins Region, Chile, since it hosts in its eastern area one of the major Cu-Mo producing mines in the country, is to establish and explain relationships between the chemical compositions of the Earth's surface and potential contaminants sources such as mining industry, agriculture and urban activity. A total of 109 samples of urban, peri-urban and rural soils were analyzed with X-ray fluorescence to determine most of the elemental concentrations analyzed. The C and S analyses were performed with the high-temperature combustion method, and a MERCUR mercury analyzer was used for Hg. The study shows that the distribution patterns for most major elements and some trace elements are controlled by the lithologic substrate. This study identified areas with metals and metalloids in high concentrations, which are a risk to the environment and health according to established international regulations. Some of these components correspond to Cu (2500 ppm), Mo (26,5 ppm), As (134,6 ppm), Cr (206.6 ppm), Hg (0.2 ppm), Ni (26.4 ppm), Pb (61.7 ppm), V (227,2 ppm) and Zn (180.3 ppm). Through an elementary association analysis, most of these elements resulted from extractive activities of Cu, metal alloys and oil combustion. It was also possible to trace the use of fertilizers and pesticides in agricultural soils, as well as the combustion of oil related to vehicles in the study area. This information is relevant to implement environmental management strategies to control possible exposure to toxic compounds to human health.

Survey of six metal contaminants and impurities and eleven metals and alloy components released from stainless-steel sheets on the Chinese market.

The release of metal elements from stainless-steel products in contact with food may endanger human health. To protect human health, different countries or international organisations have formulated corresponding regulations or technical guidelines. Limits for only five metal elements are stipulated in the China National Food Safety Standard (GB 4806.9) and food simulants and test conditions are fixed regardless of the actual use condition. In this study, inductively coupled plasma mass spectroscopy and inductively coupled plasma optical emission spectroscopy were used to measure the concentrations of six metal contaminants and impurities and 11 metals and alloy component released from stainless-steel sheets on Chinese market. The effects were also investigated on metal release of six grades (201, 202, 304, 430, 443, and 30Cr13) and 6 exposure conditions (food simulant 5 g L-1 citric acid or 4 vol% acetic acid, contact temperature 70 °C or 100 °C, and contact time 2 h, 0.5 h, or 0.5 h followed by ambient temperature for 24 h). For reusable stainless-steel sheets, especially for grade 30Cr13, it was essential to perform three consecutive release tests to check compliance. However, there was no need to conduct three consecutive release tests for the other five grades if the results of the first test met the regulations. It was recommended that 5 g L-1 citric acid should be used as food simulant and contact temperature and time should be based on the actual using conditions. No relationships were found between metal release amounts and contact test temperature or time. The specific release limits for Pb, Cr, As, Cd, and Ni should be lowered and Al, Mn, and Fe be added in GB 4806.9. The results of this study can be a reference for further analysis of the release behaviour of metal elements in actual stainless-steel products.

Inflammatory and coagulatory markers and exposure to different size fractions of particle mass, number and surface area air concentrations in the Swedish hard metal industry, in particular to cobalt.

PURPOSE: To study the relationship between inhalation of airborne particles and cobalt in the Swedish hard metal industry and markers of inflammation and coagulation in blood. METHODS: Personal sampling of inhalable cobalt and dust were performed for subjects in two Swedish hard metal plants. Stationary measurements were used to study concentrations of inhalable, respirable, and total dust and cobalt, PM10 and PM2.5, the particle surface area and the particle number concentrations. The inflammatory markers CC16, TNF, IL-6, IL-8, IL-10, SAA and CRP, and the coagulatory markers FVIII, vWF, fibrinogen, PAI-1 and D-dimer were measured. A complete sampling was performed on the second or third day of a working week following a work-free weekend, and additional sampling was taken on the fourth or fifth day. The mixed model analysis was used, including covariates. RESULTS: The average air concentrations of inhalable dust and cobalt were 0.11 mg/m3 and 0.003 mg/m3, respectively. For some mass-based exposure measures of cobalt and total dust, statistically significant increased levels of FVIII, vWF and CC16 were found. CONCLUSIONS: The observed relationships between particle exposure and coagulatory biomarkers may indicate an increased risk of cardiovascular disease.

Carcinogenic hazard assessment of cobalt-containing alloys in medical devices: Review of in vivo studies.

Cobalt (Co) alloys have been used for over seven decades in a wide range of medical devices, including, but not limited to, hip and knee implants, surgical tools, and vascular stents, due to their favorable biocompatibility, durability, and mechanical properties. A recent regulatory hazard classification review by the European Chemicals Agency (ECHA) resulted in the classification of metallic Co as a Class 1B Carcinogen (presumed to have carcinogenic potential for humans), primarily based on inhalation rodent carcinogenicity studies with pure metallic Co. The ECHA review did not specifically consider the carcinogenicity hazard potential of forms or routes of Co that are relevant for medical devices. The purpose of this review is to present a comprehensive assessment of the available in vivo preclinical data on the carcinogenic hazard potential of exposure to Co-containing alloys (CoCA) in medical devices by relevant routes. In vivo data were reviewed from 33 preclinical studies that examined the impact of Co exposure on local and systemic tumor incidence in rats, mice, guinea pigs, and hamsters. Across these studies, there was no significant increase of local or systemic tumors in studies relevant for medical devices. Taken together, the relevant in vivo data led to the conclusion that CoCA in medical devices are not a carcinogenic hazard in available in vivo models. While specific patient and implant factors cannot be fully replicated using in vivo models, the available in vivo preclinical data support that CoCA in medical devices are unlikely a carcinogenic hazard to patients.

Tissue responses after implantation of biodegradable Mg alloys evaluated by multimodality 3D micro-bioimaging in vivo.

The local response of tissue triggered by implantation of degradable magnesium-based implant materials was investigated in vivo in a murine model. Pins (5.0 mm length by 0.5 mm diameter) made of Mg, Mg-10Gd, and Ti were implanted in the leg muscle tissue of C57Bl/6N mice (n = 6). Implantation was generally well tolerated as documented by only a mild short term increase in a multidimensional scoring index. Lack of difference between the groups indicated that the response was systemic and surgery related rather than material dependent. Longitudinal in vivo monitoring utilizing micro-computed tomography over 42 days demonstrated the highest and most heterogeneous degradation for Mg-10Gd. Elemental imaging of the explants by micro X-ray fluorescence spectrometry showed a dense calcium-phosphate-containing degradation layer. In order to monitor resulting surgery induced and/or implant material associated local cell stress, sphingomyelin based liposomes containing indocyanine green were administered. An initial increase in fluorescent signals (3-7 days after implantation) indicating cell stress at the site of the implantation was measured by in vivo fluorescent molecular tomography. The signal decreased until the 42nd day for all materials. These findings demonstrate that Mg based implants are well tolerated causing only mild and short term adverse reactions.

Copper alloys' metal migration and bioaccessibility in saliva and gastric fluid.

The oral bioaccessibility of copper alloys and pure metals was assessed using in vitro methods with synthetic saliva and gastric fluid. The metal-specific migration rates from polished alloy surfaces are higher in gastric (pH 1.5) than in saliva fluid (pH 7.2). In both media, migrations are higher for lead than for other metals. The bioaccessible metal concentrations in massive copper alloys, after 2 h in gastric fluid, was only <0.01%-0.18%, consistent with the low surface reactivity of copper alloys (defined as 1 mm spheres). The average metal-specific migrations of cobalt, copper, nickel and lead from most of the tested copper alloys in gastric media are comparable to the ones from their pure metals. The data further show that the bioaccessibility of metals in massive copper alloys primarily depends on the bioelution medium, the exposed surface area and the composition of the alloy. The tested copper alloys show only limited evidence for influence of alloy surface microstructure. This is contrary to findings for other alloys such as stainless steel. Additional investigations on other copper alloys could allow to further refine these conclusions. These findings are useful for establishing the hazard and risk profile of copper alloys following oral exposure.

Estimates of environmental loading from copper alloy materials.

Metal release rates were measured from four different copper alloy-based materials used by the aquaculture industry: copper sheet machined into a diamond mesh, copper alloy mesh (CAM), silicon bronze welded wire mesh, and copper sheeting, and compared with conventional nylon aquaculture net treated with a cuprous oxide antifouling (AF) coating. Release rates were measured in situ in San Diego Bay using a Navy-developed Dome enclosure system at nine different time points over one year. As expected, copper was the predominant metal released, followed by zinc and nickel, which were fractional components of the materials tested. Release rates followed a temporal trend similar to those observed with copper AF coatings applied to vessel hulls: an initial spike in copper release was followed by a decline to an asymptotic low. Leachate toxicity was consistent with prior studies and was directly related to the metal concentrations, indicating the alloys tested had no additional toxicity above pure metals.

Titanium Alloy Intramedullary Nails and Plates Affect Serum Metal Ion Levels within the Fracture Healing Period.

Titanium alloy implants are the most used materials for the fixation of lower extremity fractures. Although these implants were thought to be inert materials in vitro, several studies have shown increased serum and remote tissue metal ion levels due to wear of implants and friction of the bone-implant interface in vivo. The aim of this study was to investigate the alteration of serum metal ion levels that are released from intramedullary nails and plates used for the fixation of lower extremity fractures, within the fracture healing period. The study included 20 adult patients, who were treated with intramedullary nail or plate osteosynthesis due to closed lower extremity fractures. Alterations of serum titanium, aluminum, molybdenum, and vanadium levels were evaluated at 6, 12, 18, and 24 weeks postoperatively. A statistically significant increase was determined in serum titanium, aluminum, molybdenum, and vanadium ion levels in the intramedullary nail and plate groups at the end of the follow-up period. Pairwise comparisons of metal ion levels between implant groups revealed no significant difference during a 24-week follow-up period. Compared to the control group, statistically significant increased levels of serum titanium, aluminum, vanadium, and molybdenum ions were determined in the implant groups used for the fixation of lower extremity fractures at the end of 24 weeks. In the current literature, the potential toxic effects of prolonged exposure to low levels of these metal ions are still unknown. It can be predicted that long-term metal ion exposure could result in vivo pathological processes in the future.

Bioaccessibility of nickel and cobalt in powders and massive forms of stainless steel, nickel- or cobalt-based alloys, and nickel and cobalt metals in artificial sweat.

Nickel (Ni) and cobalt (Co) are the most common metal allergens upon skin contact at occupational settings and during consumer handling of metals and alloys. A standardized test (EN, 1811) exists to assess Ni release from articles of metals and alloys in massive forms intended for direct and prolonged skin contact, but no corresponding test exists for other materials such as powders or massive forms of alloys placed on the market or to determine the release of Co, for which only limited data is available. Differences in Ni and Co release from massive forms of a range of common stainless steels and some high-alloyed grades compared to Ni and Co metals were therefore assessed in artificial sweat for 1 week at 30 °C according to EN 1811. A comparable modified test procedure was elaborated and used for powders and some selected massive alloys. All alloys investigated released significantly less amount of Ni (100-5000-fold) and Co (200-400,000-fold) compared with Ni and Co metal, respectively. Almost all alloys showed a lower bioaccessible concentration (0.007-6.8 wt% Ni and 0.00003-0.6 wt% Co) when compared to corresponding bulk alloy contents (0.1-53 wt% Ni, 0.02-65 wt% Co). Observed differences are, among other factors, related to differences in bulk composition and to surface oxide characteristics. For the powders, less Ni and Co were released per surface area, but more per mass, compared to the corresponding massive forms.

Assessing the contributions of metals in environmental media to exposure biomarkers in a region of ferroalloy industry.

Residential proximity to ferroalloy production has been associated with increased manganese exposure, which can adversely affect health, particularly among children. Little is known, however, about which environmental samples contribute most to internal levels of manganese and other ferroalloy metals. We aimed to characterize sources of exposure to metals and evaluate the ability of internal biomarkers to reflect exposures from environmental media. In 717 Italian adolescents residing near ferromanganese industry, we examined associations between manganese, lead, chromium, and copper in environmental samples (airborne particles, surface soil, indoor/outdoor house dust) and biological samples (blood, hair, nails, saliva, urine). In multivariable regression analyses adjusted for child age and sex, a 10% increase in soil Mn was associated with increases of 3.0% (95% CI: 1.1%, 4.9%) in nail Mn and 1.6% (95% CI: -0.2%, 3.4%) in saliva Mn. Weighted-quantile-sum (WQS) regression estimated that higher soil and outdoor dust Mn accounted for most of the effect on nail Mn (WQS weights: 0.61 and 0.22, respectively, out of a total of 1.0). Higher air and soil Mn accounted for most of the effect on saliva Mn (WQS weights: 0.65 and 0.29, respectively). These findings can help inform biomarker selection in future epidemiologic studies and guide intervention strategies in exposed populations.

The lead ores circulation in Central China during the early Western Han Dynasty: A case study with bronze vessels from the Gejiagou site.

This study first publishes lead isotope data of bronze vessels from Central China in Western Han Dynasty and attempts to find out the lead ores circulation of this time by taking bronzes from the Gejiagou site (Nanyang City, Henan Province) as an example. The elemental concentrations suggest the lead should be introduced on purpose and indicate the provenance information of lead ores. All the lead isotope ratios conform to the characteristics of common lead and most of them are similar to Nanyang local lead ores. The lead of another two bronzes, NY9 and NY13, should be imported from southern China. Combined with the historical background of early Western Han Dynasty, the wider range of the lead ore circulation may be an indicator for, as the loose policy, economic prosperity and transportation improvement.

A step towards intelligent EBSD microscopy: machine-learning prediction of twin activity in MgAZ31.

Although microscopy is often treated as a quasi-static exercise for obtaining a snapshot of events and structure, it is clear that a more dynamic approach, involving real-time decision making for guiding the investigation process, may provide deeper insights, more efficiently. On the other hand, many applications of machine learning involve the interpretation of local circumstances from experience gained over many observations; that is, machine learning potentially provides an ideal solution for more efficient microscopy. This paper explores the potential for informing the microscope's observation strategy while characterising critical events. In particular, the identification of regions likely to experience twin activity (twin interaction with grain boundary) in AZ31 magnesium is attempted, from only local information. EBSD-based observations in the neighbourhoods of twin activity are fed into a machine-learning environment to inform the future search for such events, and the accuracy of the resultant decisions is quantified relative to the number of prior observations. The potential for utilising different types of local information, and their resultant value in the prediction process, is also assessed. After applying an attribute selection filter, and various other machine-learning tools, a decision-tree model is able to classify likely neighbourhoods of twin activity with 85% accuracy. The resultant framework provides the first step towards an intelligent microscopy for efficient observation of stochastic events during in situ microscopy campaigns. LAY DESCRIPTION: One role of artificial intelligence is to predict future events after learning from many previous observations. In materials science, various phenomena (such as crack nucleation) are difficult to predict because they have been insufficiently observed. Furthermore, observation is difficult, precisely because their location cannot be predicted, leading to a chicken and egg conundrum. This paper applies machine learning to the search for twin nucleation sites in a magnesium alloy, in an attempt to guide the observation of twin nucleation events in a microscope based on previous observations. As more data is obtained, the accuracy of the location prediction will increase. In the current case, the machine-learning tool achieved 85% accuracy for predicting the location of twin interactions with grain boundaries after several thousand observations. The resultant framework provides the first step towards an intelligent microscopy for efficient observation of stochastic events during in situ microscopy campaigns.

A unique hybrid-structured surface produced by rapid electrochemical anodization enhances bio-corrosion resistance and bone cell responses of ß-type Ti-24Nb-4Zr-8Sn alloy.

Ti-24Nb-4Zr-8Sn (Ti2448), a new ß-type Ti alloy, consists of nontoxic elements and exhibits a low uniaxial tensile elastic modulus of approximately 45 GPa for biomedical implant applications. Nevertheless, the bio-corrosion resistance and biocompatibility of Ti2448 alloys must be improved for long-term clinical use. In this study, a rapid electrochemical anodization treatment was used on Ti2448 alloys to enhance the bio-corrosion resistance and bone cell responses by altering the surface characteristics. The proposed anodization process produces a unique hybrid oxide layer (thickness 50-120 nm) comprising a mesoporous outer section and a dense inner section. Experiment results show that the dense inner section enhances the bio-corrosion resistance. Moreover, the mesoporous surface topography, which is on a similar scale as various biological species, improves the wettability, protein adsorption, focal adhesion complex formation and bone cell differentiation. Outside-in signals can be triggered through the interaction of integrins with the mesoporous topography to form the focal adhesion complex and to further induce osteogenic differentiation pathway. These results demonstrate that the proposed electrochemical anodization process for Ti2448 alloys with a low uniaxial tensile elastic modulus has the potential for biomedical implant applications.

Electrochemical testing of a novel alloy in natural and artificial body fluids.

There is a recent trend in tissue engineering and regenerative medicine to use nanotechnology and bionanomaterials to obtain materials that mimic the surface properties of a natural tissue. From this perspective, nanolevel tissue engineering can be viewed as a novel anatomy of the future. In this paper, a novel titanium-based alloy is studied following this strategy. The alloy nanostructuration is proposed as an improved alternative for restorative prosthodontics or an implantable biomaterial. Tests in (i) standard solution of simulated body fluid (SBF) and (ii) natural saliva were performed to investigate the alloy's electrochemical stability. The results show that nanochannel growth on the alloy surface confers a higher stability than that of the untreated one in both natural and simulated environments.

Synchrotron analysis of human organ tissue exposed to implant material.

BACKGROUND: Orthopaedic implants made of cobalt-chromium alloy undergo wear and corrosion that can lead to deposition of cobalt and chromium in vital organs. Elevated cardiac tissue cobalt levels are associated with myocardial injury while chromium is a well-established genotoxin. Though metal composition of tissues surrounding hip implants has been established, few investigators attempted to characterize the metal deposits in systemic tissues of total joint arthroplasty patients. METHODS: We report the first use of micro-X-ray fluorescence coupled with micro-X-ray absorption spectroscopy to probe distribution and chemical form of cobalt, chromium and titanium in postmortem samples of splenic, hepatic and cardiac tissue of patients with metal-on-polyethylene hip implants (n = 5). RESULTS: Majority of the cobalt was in the 2+ oxidation state, while titanium was present exclusively as titanium dioxide, in either rutile or anatase crystal structure. Chromium was found in a range of forms including a highly oxidised, carcinogenic species (CrV/VI), which has never been identified in human tissue before. CONCLUSIONS: Carcinogenic forms of chromium might arise in vital organs of total joint arthroplasty patients. Further studies are warranted with patients with metal-on-metal implants, which tend to have an increased release of cobalt and chromium compared to metal-on-polyethylene hips.

Mortality Among Hardmetal Production Workers: Swedish Measurement Data and Exposure Assessment.

BACKGROUND: Mortality pattern was determined in a cohort of 16,999 white and blue-collar workers in the Swedish hardmetal industry. Exposure assessment for cobalt is presented. METHODS: A historical database (1970 to 2012) of personal and area measurements of cobalt, tungsten, and nickel in the Swedish hardmetal industry was created. Log linear and exponential modeling of cobalt concentrations based on time period, job, and site was performed, and cumulative and mean exposures were calculated. RESULTS: Some 37% of the personal cobalt measurements exceeded 0.02 mg/m, mostly for powder production, pressing, and shaping. The log linear regression showed statistical differences (P < 0.05) between sites, time periods, and jobs. Some 1.6% of the cobalt cumulative exposures for blue-collar workers exceeded 0.4 mg/m years. CONCLUSION: Low levels of cumulative and mean exposures were determined.

Determination of Thermodynamic Properties of Alkaline Earth-liquid Metal Alloys Using the Electromotive Force Technique.

A novel electrochemical cell based on a CaF2 solid-state electrolyte has been developed to measure the electromotive force (emf) of binary alkaline earth-liquid metal alloys as functions of both composition and temperature in order to acquire thermodynamic data. The cell consists of a chemically stable solid-state CaF2-AF2 electrolyte (where A is the alkaline-earth element such as Ca, Sr, or Ba), with binary A-B alloy (where B is the liquid metal such as Bi or Sb) working electrodes, and a pure A metal reference electrode. Emf data are collected over a temperature range of 723 K to 1,123 K in 25 K increments for multiple alloy compositions per experiment and the results are analyzed to yield activity values, phase transition temperatures, and partial molar entropies/enthalpies for each composition.

New Ti-Ta-Zr-Nb alloys with ultrahigh strength for potential orthopedic implant applications.

In this study, a new series of Ti-Ta-Zr-Nb alloys (Ti-38.3Ta-22Zr-8.1Nb, Ti-38.9Ta-25Zr-5Nb, Ti-39.5Ta-28Zr-2.5Nb, designated TTZN-1, TTZN-2, TTZN-3, respectively) with high elastic strain and high mechanical strength have been developed as alternatives to conventional orthopedic implant materials. The TTZN alloys have been designed using the electronic parameters of the alloying elements, combined with the approaches of the electron-to-atom ratio (e/a) and molybdenum equivalence (Moeq). X-ray diffraction analysis has revealed that all the TTZN alloys are comprised of a single ß phase, however, transmission electron microscopy observations revealed that ω and ß phases co-existed in the microstructure. The compression strains of the TTZN alloys range from 22% to 36% and the compression strength from 1787 to 1807MPa. The tensile Young's modulus, elastic strain and yield strength are 73.12 ± 4.43, 74.98 ± 2.19 and 76.62 ± 2.38 (GPa); 1.57 ± 0.27, 1.25 ± 0.27 and 1.29 ± 0.16 (%); and 1107.42 ± 144.68, 932.11 ± 195.22 and 953.58 ± 120.76MPa for TTZN-1, TTZN-2 and TTZN-3, respectively. Further, all the TTZN alloys exhibit excellent cytocompatibility as their cell adhesion density is higher than that of CP-Ti. This study demonstrates that these TTZN alloys can be anticipated to be promising candidate for orthopedic implant materials due to their high mechanical strength and high elastic strain.