Viability and Proliferation Assessment of Gingival Fibroblasts Cultured on Silver Nanoparticle-Doped Ti-6Al-4V Surfaces.

PURPOSE: To investigate the biocompatibility of silver nanoparticle (AgNP)-doped Ti-6Al-4V surfaces by evaluating the viability and proliferation rate of human gingival fibroblasts (HGFs)-as the dominant cells of peri-implant soft tissues-seeded on the modified surfaces. MATERIALS AND METHODS: AgNPs (sizes 8 nm and 30 nm) were incorporated onto Ti-6Al-4V specimen surfaces via electrochemical deposition, using colloid silver dispersions with increasing AgNP concentrations of 100 ppm, 200 ppm, and 300 ppm. One control and six experimental groups were included in the study: (1) control (Ti-6Al-4V), (2) 8 nm/100 ppm, (3) 8 nm/200 ppm, (4) 8 nm/300 ppm, (5) 30 nm/100 ppm, (6) 30 nm/200 ppm, and (7) 30 nm/300 ppm. HGF cell primary cultures were isolated from periodontally healthy donor patients and cultured in direct contact with the group specimens for 24 and 72 hours. The cytotoxicity of AgNP-doped Ti-6Al-4V specimens toward HGF was assessed by the MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) and BrdU (5-bromo-2'-deoxyuridine) assay tests. Calcein AM and ethidium homodimer (EthD-1) fluorescent stains were used to determine the live and dead cells. The morphology and attachment properties of the HGFs were determined via scanning electron microscopy (SEM). RESULTS: Energy dispersive x-ray (EDX) analysis confirmed the presence of AgNPs on the specimens. The MTT test revealed that AgNPs of both sizes and all concentrations presented a decreased cellular metabolic activity compared to the control discs. All concentrations of both sizes of AgNPs affected the cell proliferation rate compared to the control group, as revealed by the BrdU assay. Overall, cytotoxicity of the modified Ti-6Al-4V surfaces depended on cell exposure time. Observation via confocal microscopy confirmed the results of the MTT and BrdU assay tests. Specifically, most cells remained alive throughout the 72-hour culture period. SEM images revealed that adjacent cells form bonds with each other, creating confluent layers of conjugated cells. CONCLUSIONS: The findings of the present study indicate that Ti-6Al-4V surfaces modified with 8 nm and 30 nm AgNPs at concentrations of 100 ppm, 200 ppm, and 300 ppm do not produce any serious cytotoxicity toward HGFs. The initial arrest of the HGF proliferation rate recovered at 72 hours. These results on the antibacterial activity against common periodontal pathogens, in combination with the results found in a previous study by the same research group, suggest that AgNP-doped Ti-6Al-4V surfaces are potential candidates for use in implant abutments for preventing peri-implant diseases.

Health hazards of particles in additive manufacturing: a cross-disciplinary study on reactivity, toxicity and occupational exposure to two nickel-based alloys.

The increasing use of additive manufacturing (AM) techniques (e.g., 3D-printing) offers many advantages but at the same time presents some challenges. One concern is the possible exposure and health risk related to metal containing particles of different sizes. Using the nickel-based alloys Hastelloy X (HX) and Inconel 939 (IN939) as a case, the aim of this cross-disciplinary study was to increase the understanding on possible health hazards and exposure. This was done by performing in-depth characterization of virgin, reused and condensate powders, testing in vitro toxicity (cytotoxicity, genotoxicity, oxidative stress), and measuring occupational airborne exposure. The results showed limited metal release from both HX and IN939, and slightly different surface composition of reused compared to virgin powders. No or small effects on the cultured lung cells were observed when tested up to 100 µg/mL. Particle background levels in the printing facilities were generally low, but high transient peaks were observed in relation to sieving. Furthermore, during post processing with grinding, high levels of nanoparticles (> 100,000 particles/cm3) were noted. Urine metal levels in AM operators did not exceed biomonitoring action limits. Future studies should focus on understanding the toxicity of the nanoparticles formed during printing and post-processing.

Machine learning-enabled nanosafety assessment of multi-metallic alloy nanoparticles modified TiO2 system.

Establishing toxicological predictive modeling frameworks for heterogeneous nanomaterials is crucial for rapid environmental and health risk assessment. However, existing structure-toxicity correlation models for such nanomaterials are only based on simple linear regression algorithms that are prone to underfitting the training data. These models rely heavily on experimental and expensive computational quantum mechanical descriptors, which significantly limit their practical use. Herein, we present the application of empirical descriptors and complex machine learning algorithms to the development of high-performance quantitative structure-toxicity relationship (QSTR) models of TiO2 hybridized with multi-metallic (Ag, Au, Pt) alloy nanoparticles (multi-metallic NPs/TiO2). To confirm the viability of empirical descriptors as model input, we selected five distinct machine learning algorithms for predicting the toxicity of multi-metallic alloy NPs/TiO2 system in Chinese hamster ovary cell line. Notably, an empirical descriptor-based QSTR model (kernel ridge regression) revealed a predictive performance that is on par with density functional theory (DFT) descriptor-based counterparts. More specifically, the results indicated that model selection is influenced by descriptor choice, such that complex DFT descriptors worked best with a complex algorithm (random forest regression; RMSET = 0.0954, MAET = 0.0811, RT2 = 0.9411), whereas more straightforward empirical descriptors were most suitable with a simpler algorithm (kernel ridge regression; RMSET = 0.1244, MAET = 0.1106, RT2 = 0.8999). Moreover, our model outperforms existing QSAR models built on the same data set. This study offers a new perspective on using empirical features to develop accurate predictive computational models for the rapid discovery and profiling of safe-by-design nanomaterials.

Toxicity assessment and health hazard classification of stainless steels.

Stainless steels are widely used iron-based alloys that contain chromium and, typically, other alloying elements. The chromium(III)-rich surface oxide of stainless steels efficiently limits the release (bioaccessibility) of their metal constituents in most physiological environments, influencing the toxicity of the alloy. Of the constituents and impurities of stainless steels, nickel and cobalt are of particular interest, primarily due to skin sensitization and repeated-dose inhalation toxicity of nickel, and (inhalation) carcinogenicity of cobalt. A review of the available toxicological data on stainless steels, and the toxicological, mechanistic, and bioaccessibility data on their constituent metals supports the low toxicity and non-carcinogenicity of stainless steels. The comparative metal release, rather than the bulk composition of stainless steels, needs to be considered when assessing their health hazard classification according to the UN Globally Harmonized System, and the corresponding EU CLP regulation. As an illustrative example, a 28-day inhalation toxicity study on stainless steel powder showed no signs of lung toxicity at exposure levels at which significant toxicity would have been expected on the basis of its bulk nickel content. This finding is associated with the low bioaccessibility of nickel from the alloy in the lungs.

Toxicity evaluation of particles formed during 3D-printing: Cytotoxic, genotoxic, and inflammatory response in lung and macrophage models.

Additive manufacturing (AM) or "3D-printing" is a ground-breaking technology that enables the production of complex 3D parts. Its rapid growth calls for immediate toxicological investigations of possible human exposures in order to estimate occupational health risks. Several laser-based powder bed fusion AM techniques are available of which many use metal powder in the micrometer range as feedstock. Large energy input from the laser on metal powders generates several by-products, like spatter and condensate particles. Due to often altered physicochemical properties and composition, spatter and condensate particles can result in different toxicological responses compared to the original powder particles. The toxicity of such particles has, however, not yet been investigated. The aim of the present study was to investigate the toxicity of condensate/spatter particles formed and collected upon selective laser melting (SLM) printing of metal alloy powders, including a nickel-chromium-based superalloy (IN939), a nickel-based alloy (Hastelloy X, HX), a high-strength maraging steel (18Ni300), a stainless steel (316L), and a titanium alloy (Ti6Al4V). Toxicological endpoints investigated included cytotoxicity, generation of reactive oxygen species (ROS), genotoxicity (comet and micronucleus formation), and inflammatory response (cytokine/chemokine profiling) following exposure of human bronchial epithelial cells (HBEC) or monocytes/macrophages (THP-1). The results showed no or minor cytotoxicity in the doses tested (10-100 µg/mL). Furthermore, no ROS generation or formation of micronucleus was observed in the HBEC cells. However, an increase in DNA strand breaks (detected by comet assay) was noted in cells exposed to HX, IN939, and Ti6Al4V, whereas no evident release of pro-inflammatory cytokine was observed from macrophages. Particle and surface characterization showed agglomeration in solution and different surface oxide compositions compared to the nominal bulk content. The extent of released nickel was small and related to the nickel content of the surface oxides, which was largely different from the bulk content. This may explain the limited toxicity found despite the high Ni bulk content of several powders. Taken together, this study suggests relatively low acute toxicity of condensates/spatter particles formed during SLM-printing using IN939, HX, 18Ni300, 316L, and Ti6Al4V as original metal powders.

Corrosion Resistance and Cytocompatibility of Magnesium-Calcium Alloys Modified with Zinc- or Gallium-Doped Calcium Phosphate Coatings.

In orthopedic surgery, metals are preferred to support or treat damaged bones due to their high mechanical strength. However, the necessity for a second surgery for implant removal after healing creates problems. Therefore, biodegradable metals, especially magnesium (Mg), gained importance, although their extreme susceptibility to galvanic corrosion limits their applications. The focus of this study was to control the corrosion of Mg and enhance its biocompatibility. For this purpose, surfaces of magnesium-calcium (MgCa1) alloys were modified with calcium phosphate (CaP) or CaP doped with zinc (Zn) or gallium (Ga) via microarc oxidation. The effects of surface modifications on physical, chemical, and mechanical properties and corrosion resistance of the alloys were studied using surface profilometry, goniometry, scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDS), nanoindentation, and electrochemical impedance spectroscopy (EIS). The coating thickness was about 5-8 µm, with grain sizes of 43.1 nm for CaP coating and 28.2 and 58.1 nm for Zn- and Ga-doped coatings, respectively. According to EIS measurements, the capacitive response (Yc) decreased from 11.29 to 8.72 and 0.15 Ω-1 cm-2 sn upon doping with Zn and Ga, respectively. The Ecorr value, which was -1933 mV for CaP-coated samples, was found significantly electropositive at -275 mV for Ga-doped ones. All samples were cytocompatible according to indirect tests. In vitro culture with Saos-2 cells led to changes in the surface compositions of the alloys. The numbers of cells attached to the Zn-doped (2.6 × 104 cells/cm2) and Ga-doped (6.3 × 104 cells/cm2) coatings were higher than that on the surface of the undoped coating (1.0 × 103 cells/cm2). Decreased corrosivity and enhanced cell affinity of the modified MgCa alloys (CaP coated and Zn and Ga doped, with Ga-doped ones having the greatest positive effect) make them novel and promising candidates as biodegradable metallic implant materials for the treatment of bone damages and other orthopedic applications.

Ecological safety with multifunctional applications of biogenic mono and bimetallic (Au-Ag) alloy nanoparticles.

Recently, the design and biosynthesis of metallic nanoparticles (NPs) have drawn immense interest, but their very specific function and secondary toxic effects are major concern towards commercial application of NPs. That's why environment-friendly (nontoxic) NPs having multiple functions are extremely important. Herein, we report the mechanism of biosynthesis of mono and bimetallic (Au-Ag) alloy NPs and study their multifunctional (antioxidant, antifungal and catalytic) activity and ecotoxicological property. AgNPs exhibit phytotoxicity (at 100 µg/ml) on morphological characteristics of Lentil (during germination), while alloy and AuNPs are non-toxic (up to 100 µg/ml). In-vitro antioxidant response using DPPH methods reveals that alloy NPs (IC50 = 55.8 µg/ml) possesses better antioxidant activity compared to the monometallic NPs (IC50 = 73.6-82.6 µg/ml). In addition, alloy NPs displayed appreciable antifungal efficacy against a plant pathogenic fungus Gloeosporium musarum by structural damage to hyphae and conidia of the fungus. The catalytic performance of NPs for degradation of chlorpyriphos (CP) pesticide reveals that alloy NPs is more efficient in terms of rate constant (k = 0.405 d-1) and half-life (T50 = 1.71 d) compared to the monometallic counterparts (k = 0.115-0.178 d-1; T50 = 3.89-6.04 d). Degradation products of CP (3,5,6-trichloropyridinol and diethyl thiophosphate) are confirmed using mass spectrometry and based on that a degradation pathway has been suggested. Thus, these sustainable and ecological safe biogenic (Au-Ag) alloy NPs promise multiple applications as an antioxidant in the pharmaceutical sector, as a fungicide for disease control in agriculture, as a catalyst for remediation of toxic pollutants and in other pertinent areas.

Comparison of Biocompatibility of Three Soft Milled Cobalt-Chromium Alloys.

In the context of biology and medicine, nanotechnology encompasses the materials, devices, and systems whose structure and function are relevant for small length scales, from nanometers through microns. The purpose of this study was to compare the microstructures and resultant biocompatibility of three commercially available soft milled cobalt-chromium (Co-Cr) alloys (Ceramill Sintron, CS; Sintermetall, SML; and Soft Metal, SM). Disc-shaped specimens were prepared by milling the soft blanks and subsequent post-sintering. The crystal and microstructures of the three different alloys were studied using optical microscopy, X-ray diffractometry (XRD), energy dispersive X-ray spectroscopy, and electron backscatter diffraction. The amounts of Co, Cr, and molybdenum (Mo) ions released from the alloys were evaluated using inductively coupled plasma-mass spectroscopy. The effect of ion release on the viability of L929 mouse fibroblasts was evaluated by a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. The SML alloy showed a finer grain size (approx. 5 µm) and a larger pore size (approx. 5 µm) than the CS and SM alloys, and its XRD pattern exhibited a slightly higher ε phase peak intensity than that of the γ phase. In the CS and SML alloys, the average crystallite sizes of the nano-sized Cr23C6 carbide were 21.6 and 19.3 nm, respectively. The SML alloy showed higher concentrations of Cr and Mo in the grain boundaries than the other two alloys. The SML alloy showed significantly higher Co and Mo ion releases (p < 0.001) and significantly lower cell viability (p < 0.05) than the CS and SM alloys. The combined results of this in vitro study suggest that the three soft milled Co-Cr alloys had different crystal and microstructures and, as a result, different levels of in vitro biocompatibility.

Physical and biological characterizations of TiNbSn/(Mg) system produced by powder metallurgy for use as prostheses material.

Titanium scaffolds with non-toxic ß stabilizing elements (Nb and Sn), Ti-34Nb-6Sn (TNS), and with magnesium as spacer (TNS/M), were processed by powder metallurgy, and sintered at 800 °C. The X-ray diffraction (XRD) pattern showed that materials are biphasic alloys, presenting 45 to 42% (wt %) in hcp (α-phase) and the rest is bcc (ß-phase), and the presence of a slight peak relating to TiO2 in both materials. Pores of approximately 50 µm for TNS and 300 µm to TNS/M were observed in the micrographic analysis by scanning electron microscopy (SEM). The wettability was higher for TNS/M compared to TNS. The elastic modulus was higher for TNS compared to TNS/M. Stem cells derived from equine bone marrow (BMMSCs) were used for in vitro assays. The morphologic and adhesion evaluation after 72 h, carried out by direct contact assay with the materials showed that the BMMSCs were anchored and adhered to the porous scaffolds, in the way the cytoplasmic extension was observed. The cellular migration, using the "wound healing" method, was significant for the groups treated with conditioned medium with materials in 24 h. Osteogenic differentiation of BMMSCs, assessed by calcium deposition and staining with Alizarin Red, was greater in the conditioned medium with TNS/M in 10 days of culture. Since the biological effects was good and the elastic modulus decreased in the system with magnesium is a promising new content titanium alloy for biomedical application.

Fabrication, characterization, and in vivo biocompatibility evaluation of titanium-niobium implants.

In this study, biocompatible titanium-niobium (Ti-Nb) alloys were fabricated by using powder metallurgy methods. Physical, morphological, thermal, and mechanical analyses were performed and their in vivo compatibility was evaluated. Besides α, ß, and α″ martensitic phases, α+ß Widmanstätten phase due to increasing sintering temperature was seen in the microstructure of the alloys. Phase transformation temperatures of the samples decreased as Nb content increased. The ratio of Nb in the samples affected their mechanical properties. No toxic effect was observed on implanted sites. This study shows that Ti-Nb alloys can be potentially used for orthopedic applications without any toxic effects.

Improvements of Corrosion Resistance and Antibacterial Properties of Hydroxyapatite/Cupric Oxide Doped Titania Composite Coatings on Degradable Magnesium Alloys.

The excellent biocompatibility of calcium phosphate (CaP) coatings makes them widely used in magnesium (Mg) alloy orthopedic implant materials. However, the porous morphology of CaP coatings limits their corrosion resistance. A cupric oxide (CuO) doped titania (TiO2) sol-gel coating is prepared on a porous hydroxyapatite (HA) coating. According to electrochemical test results, the HA/CuO-TiO2 coating obtains a current density of 6 × 10-4 mA/cm2, lower than that of the Mg alloy (2.6 × 10-2 mA/cm2). The hydrogen evaluation of the HA/CuO-TiO2 coating is only 1/12 that of the Mg alloy after immersion for 7 days. In addition, the HA/CuO-TiO2 coating has an antibacterial rate of 99.5 ± 0.4% against Staphylococcus aureus, significantly higher than that of the HA coating (19.8 ± 0.3%) and HTC0 coating (38.4 ± 0.5%). The CuO doped composite coating has no adverse effect or cytotoxicity on cell proliferation (cell viability ≥79.6%). Hence, the HA/CuO-TiO2 composite coating is useful for enhancing the corrosion resistance and antibacterial properties of Mg alloys while ensuring cytocompatibility. The HA/CuO-TiO2 coated AZ60 Mg alloy can meet the requirements of clinical application.

TiO2-Induced In Situ Reaction in Graphene Oxide-Reinforced AZ61 Biocomposites to Enhance the Interfacial Bonding.

Graphene oxide (GO) can improve the degradation resistance of biomedical Mg alloy because of its excellent impermeability and outstanding chemical inertness. However, the weak interfacial bonding between GO and Mg matrix leads to easily detaching during degradation. In this study, in situ reaction induced by TiO2 took place in the AZ61-GO biocomposite to enhance the interfacial bonding between GO and Mg matrix. For the specific process, TiO2 was uniformly and tightly deposited onto the GO surface by hydrothermal reaction (TiO2/GO) first and then used for fabricating AZ61-TiO2/GO biocomposites by selective laser melting (SLM). Results showed that TiO2 was in situ reduced by magnesiothermic reaction during SLM process, and the reduzate Ti, on the one hand, reacted with Al in the AZ61 matrix to form TiAl2 and, on the other hand, reacted with GO to form TiC at the AZ61-GO interface. Owing to the enhanced interfacial bonding, the AZ61-TiO2/GO biocomposite showed 12.5% decrease in degradation rate and 10.1% increase in compressive strength as compared with the AZ61-GO biocomposite. Moreover, the AZ61-TiO2/GO biocomposite also showed good cytocompatibility because of the slowed degradation. These findings may provide guidance for the interfacial enhancement in GO/metal composites for biomedical applications.

Microstructure controls the corrosion behavior of a lean biodegradable Mg-2Zn alloy.

Microstructural design was a long-term sustainable development method to improve the biodegradability and mechanical properties of low alloyed biomedical Mg alloys. In this study, the microstructural features (including grain size, deformation twin, deformed grains, sub-grains, and recrystallized grains) of the MZ2 ((Mg-2Zn (wt%)) alloy were controlled by different single-passed rolling reductions at high temperature. Besides the effect of grain size, we found that deformation twins and deformed grains influenced corrosion performance. Grain refinement with uniform distribution, meanwhile reducing the content of deformation twins, deformed grains, and sub-grains, was a practical method to improve both corrosion resistance and mechanical properties of MZ2 alloy. This finding proposed a better understanding of the development of lean biomedical Mg alloys with superior mechanical properties and favorable corrosion resistance. STATEMENT OF SIGNIFICANCE: Current research and development of biomedical Mg focused on alloying methods. The lean biodegradable Mg, which reduced the materials' compositional complexity, was the benefit of development for long-term sustainability. Here, our work revealed the relationship between microstructural features and corrosion resistance of a lean Mg-2Zn alloy during the different single-passed rolling processes. We found that recrystallized fine grains with partially ultra-fine grains could improve both strength and corrosion resistance. This study could give a new understanding of the development of lean biodegradable Mg alloys by using microstructural design to improve the overall performance of biomedical applications.

Corrosion resistance of a Nitinol ocular microstent: Implications on biocompatibility.

Nitinol is commonly used in medical implants due to its unique thermomechanical properties of shape memory and superelasticity. Free nickel has the potential to induce biological responses that may be a concern for permanent implants manufactured from nickel-containing alloys. Although there are extensive reports on the effects of surface treatments on corrosion behavior in cardiovascular Nitinol implants, there is a lack of data on corrosion resistance and impact on biocompatibility for ocular implants. Therefore, the objective of this study was to determine localized corrosion and nickel elution resistance of an electropolished Nitinol-based ocular device (Hydrus Microstent, Ivantis, Inc.) intended for patients with primary open angle glaucoma. Pitting corrosion susceptibility was characterized by potentiodynamic polarization testing per ASTM F2129. In addition, nickel ion release was quantified with immersion testing to 63 days. The results indicated high localized corrosion resistance as all samples reached polarization potentials of 800 mV without pitting initiation. Maximum nickel elution rates per device were less than approximately 1.1 ng/device/day after the first day of immersion and reduced to less than 0.1 ng/device/day after 7 days. For a patient with bilateral microstents, these nickel concentrations are ×10,000 lower than previously published tolerable intake levels for systemic toxicity. Overall, these corrosion results are in good agreement with literature values of well processed and biocompatible Nitinol devices indicating adverse systemic biological responses are not expected in vivo.

The bioeffects of degradable products derived from a biodegradable Mg-based alloy in macrophages via heterophagy.

Biodegradable magnesium alloys are promising candidates for use in biomedical applications. However, degradable particles (DPs) derived from Mg-based alloys have been observed in tissue in proximity to sites of implantation, which might result in unexpected effects. Although previous in vitro studies have found that macrophages can take up DPs, little is known about the potential phagocytic pathway and the mechanism that processes DPs in cells. Additionally, it is necessary to estimate the potential bioeffects of DPs on macrophages. Thus, in this study, DPs were generated from a Mg-2.1Nd-0.2Zn-0.5Zr alloy (JDBM) by an electrochemical method, and then macrophages were incubated with the DPs to reveal the potential impact. The results showed that the cell viability of macrophages decreased in a concentration-dependent manner in the presence of DPs due to effects of an apoptotic pathway. However, the DPs were phagocytosed into the cytoplasm of macrophages and further degraded in phagolysosomes, which comprised lysosomes and phagosomes, by heterophagy instead of autophagy. Furthermore, several pro-inflammatory cytokines in macrophages were upregulated by DPs through the induction of reactive oxygen species (ROS) production. To the best of our knowledge, this is the first study to show that DPs derived from a Mg-based alloy are consistently degraded in phagolysosomes after phagocytosis by macrophages via heterophagy, which results in an inflammatory response owing to ROS overproduction. Thus, our research has increased the knowledge of the metabolism of biodegradable Mg metal, which will contribute to an understanding of the health effects of biodegradable magnesium metal implants used for tissue repair. STATEMENT OF SIGNIFICANCE: Biomedical degradable Mg-based alloys have great promise in applied medicine. Although previous studies have found that macrophages can uptake degradable particles (DPs) in vitro and observed in the sites of implantation in vivoin vivo, few studies have been carried out on the potential bioeffects relationship between DPs and macrophages. In this study, we analyzed the bioeffects of DPs derived from a Mg-based alloy on the macrophages. We illustrated that the DPs were size-dependently engulfed by macrophages via heterophagy and further degraded in the phagolysosome rather than autophagosome. Furthermore, DPs were able to induce a slight inflammatory response in macrophages by inducing ROS production. Thus, our research enhances the knowledge of the interaction between DPs of Mg-based alloy and cells, and offers a new perspective regarding the use of biodegradable alloys.

A biodegradable Zn-1Cu-0.1Ti alloy with antibacterial properties for orthopedic applications.

Zinc (Zn) alloys are receiving increasing attention in the field of biodegradable implant materials due to their unique combination of suitable biodegradability and good biological functionalities. However, the currently existing industrial Zn alloys are not necessarily biocompatible, nor sufficiently mechanically strong and wear-resistant. In this study, a Zn-1Cu-0.1Ti alloy is developed with enhanced mechanical strength, corrosion wear property, biocompatibility, and antibacterial ability for biodegradable implant material applications. HR and HR + CR were performed on the as-cast alloy and its microstructure, mechanical properties, frictional and wear behaviors, corrosion resistance, in vitro cytocompatibility, and antibacterial ability were systematically assessed. The microstructures of the Zn-1Cu-0.1Ti alloy after different deformation conditions included a η-Zn phase, a ε-CuZn5 phase, and an intermetallic phase of TiZn16. The HR+CR sample of Zn-1Cu-0.1Ti exhibited a yield strength of 204.2 MPa, an ultimate tensile strength of 249.9 MPa, and an elongation of 75.2%; significantly higher than those of the HR alloy and the AC alloy. The degradation rate in Hanks' solution was 0.029 mm/y for the AC alloy, 0.032 mm/y for the HR+CR alloy, and 0.034 mm/y for the HR alloy. The HR Zn-1Cu-0.1Ti alloy showed the best wear resistance, followed by the AC alloy and the alloy after HR + CR. The extract of the AC Zn-1Cu-0.1Ti alloy showed over 80% cell viability with MC3T3-E1 pre-osteoblast and MG-63 osteosarcoma cells at a concentration of ≤ 25%. The as-cast Zn-1Cu-0.1Ti alloy showed good blood compatibility and antibacterial ability. STATEMENT OF SIGNIFICANCE: This work repots a Zn-1Cu-0.1Ti alloy with enhanced mechanical strength, corrosion wear property, biocompatibility, and antibacterial ability for biodegradable implant applications. Our findings showed that Zn-1Cu-0.1Ti after hot-rolling plus cold-rolling exhibited a yield strength of 204.2 MPa, an ultimate tensile strength of 249.9 MPa, an elongation of 75.2%, and a degradation rate of 0.032 mm/y in Hanks' Solution. The hot-rolled Zn-1Cu-0.1Ti showed the best wear resistance. The extract of the as-cast alloy at a concentration of ≤ 25% showed over 80% cell viability with MC3T3-E1 and MG-63 cells. The Zn-1Cu-0.1Ti alloy showed good hemocompatibility and antibacterial ability.

Preparation, structural, microstructural, mechanical and cytotoxic characterization of as-cast Ti-25Ta-Zr alloys.

Titanium alloys have been widely used as biomaterials, especially for orthopedic prostheses and dental implants, but these materials have Young's modulus almost three times greater than human cortical bones. Because of this, new alloys are being produced for the propose of decreasing Young's modulus to achieve a more balanced mechanical compatibility with the bone. In this paper, it is reported the development of Ti-25Ta alloys as a base material, in which was introduced zirconium, with concentration varying between 0 and 40 wt%, with the aim of biomedical applications. The alloys were prepared in an arc-melting furnace. The microstructural analysis was performed by x-ray diffraction as well as optical and scanning electron microscopy. Selected mechanical properties were analyzed by microhardness and Young's modulus measurements, and cytotoxicity analysis by indirect test. X-ray measurements revealed the presence of α″ phase in the alloy without zirconium; α″ + ß phases for alloys with 10, 20, and 30 wt% of zirconium, and ß phase only for the alloy with 40 wt% of zirconium. These results were corroborated by the microscopy results. The hardness of the alloy was higher than that of cp-Ti due to the actions of zirconium and tantalum as hardening agents. The Young's modulus decreases with high levels of zirconium due to the stabilization of the ß phase. The cytotoxicity test showed that the extracts of studied alloys are not cytotoxic for osteoblast cells in short periods of culture.

Comparative in vitro study on binary Mg-RE (Sc, Y, La, Ce, Pr, Nd, Sm, Eu, Gd, Tb, Dy, Ho, Er, Tm, Yb and Lu) alloy systems.

Correct selection of alloying elements is important for developing novel biodegradable magnesium alloys with superior mechanical and biological performances. In contrast to various reports on nutrient elements (Ca, Zn, Sr, etc.) as alloying elements of biomedical magnesium alloys, there is limited information about how to choose the right rare earth elements (REEs) as alloying elements of magnesium. In this work, 16 kinds of REEs were individually added into Mg, including Sc, Y, La, Ce, Pr, Nd, Sm, Eu, Gd, Tb, Du, Ho, Er, Tm, Yb and Lu, to fabricate binary Mg-RE model alloys with different composition points. Under the same working history, comparative studies were undertaken and the impact of each kind of rare earth element on the microstructure, mechanical property, corrosion behavior and biocompatibility of Mg were investigated. The corresponding influence level for the 16 kinds of REEs were ranked. The results showed that the second phases were detected in some Mg-RE alloys, which were mainly composed of Mg12RE. By adding different REEs into Mg with proper contents, the mechanical properties of resulting Mg-RE binary alloys could be adjusted in wide range. The corrosion resistance of Mg-light REE alloys was generally better than Mg-heavy REE alloys. As for biocompatibility, Mg-RE model alloys showed no cytotoxic effect on MC3T3-E1 cells. The hemolysis rates of all experimental Mg-RE model alloys were lower than 5% except for Mg-Lu alloy model. In general, the addition of different REEs into Mg could improve its performance from different aspects. This work provides a better understanding on suitable REEs as alloying elements for magnesium, and the future R&D direction on biomedical Mg-RE alloys was proposed. STATEMENT OF SIGNIFICANCE: In contrast to various reports on nutrient elements (Ca, Zn, Sr, etc.) as alloying elements of biomedical magnesium alloys, until now there is limited information about how to choose the right rare earth elements (REEs) as alloying elements of magnesium. In this work, comparative studies were undertaken by individually adding 16 kinds of REEs, including Sc, Y, La, Ce, Pr, Nd, Sm, Eu, Gd, Tb, Du, Ho, Er, Tm, Yb and Lu, into Mg to fabricate binary Mg-RE model alloys, with different composition points, then the impact of each kind of rare earth element on the microstructure, mechanical property, corrosion behavior and biocompatibility of Mg under the same working history were investigated, and the corresponding influence level for the 16 kinds of REEs were ranked. This work provides a better understanding on suitable REEs as alloying elements for magnesium, and the future R&D direction on biomedical Mg-RE alloys was proposed.

Effect of Lithium and Aluminum on the Mechanical Properties, In Vivo and In Vitro Degradation, and Toxicity of Multiphase Ultrahigh Ductility Mg-Li-Al-Zn Quaternary Alloys for Vascular Stent Application.

Magnesium alloys are the most widely studied biodegradable metals for biodegradable vascular stent application. Two major issues with current magnesium alloy based stents are their low ductility and fast corrosion rates. Several studies have validated that introduction of Li into the magnesium alloys will significantly improve the ductility while alloying with Al will improve the corrosion resistance and strength. In the present study, we studied the effects of alloying different amounts of Li and Al on the Mg-Li-Al-Zn (LAZ) quaternary alloy system. Rods were made from four different LAZ alloys, namely, LAZ611, LAZ631, LAZ911, and LAZ931 following melting, casting, and then extrusion. Systematic assessment of mechanical properties, in vitro corrosion, cytotoxicity, and in vivo degradation including local and systemic toxicity conducted demonstrated the beneficial effects of Li and Al on the mechanical properties. Our results specifically suggest that alloying with Li significantly improved the ductility while Al enhanced the strength of the LAZ alloys. Four of the LAZ alloys exhibited different corrosion rates in Hank's balanced salt solution depending on the chemical composition. Indirect in vitro cytotoxicity tests also showed lower cytotoxicity for the alloys exhibiting higher corrosion resistance. In vivo corrosion rates in the mouse subcutaneous model showed different corrosion rates compared to the in vitro tests. Nevertheless, all of the four LAZ alloys displayed no local and systemic toxicity based on the histology analysis. This research study, therefore, demonstrated the benefits of using Li and Al as alloying elements in LAZ alloys and the potential use of LAZ alloys for vascular stent application.