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Medium-entropy Zr-Nb-Ti (ZNT) alloys are being extensively investigated as load-bearing implant materials because of their exceptional biocompatibility and corrosion resistance, and low magnetic susceptibility. Nevertheless, enhancing their yield strength while simultaneously decreasing their elastic modulus presents a formidable obstacle, significantly constraining their broader utilization as metallic biomaterials. In this study, three medium-entropy ZNT alloys, i.e., Zr 45 Nb 45 Ti 10 , Zr 42.5 Nb 42.5 Ti 15 , and Zr 40 Nb 40 Ti 20 (denoted ZNT 10 , ZNT 15 , and ZNT 20 , respectively), were designed based on the miscibility gap in the ZNT phase diagram and prepared by annealing of cold-rolled ingots. Their microstructures, mechanical properties, wear resistance, corrosion resistance, magnetic susceptibility, and biocompatibility were systematically studied. Spinodal decomposition occurred in the cold-rolled ZNT 10 and ZNTi 15 after annealing at 650 °C for 2 h and resulted in nanoscale Zr-rich β 1 and (Nb, Ti)-rich β 2 phases, which significantly improved their yield strength and reduced their elastic modulus. The wear resistance of the alloys decreased with an increase in Ti content. Dense ZrO 2 , Nb 2 O 5 , and TiO 2 oxide layers were formed during the polarization process in Hanks' solution, which enhanced the corrosion resistance of the alloys. These ZNT alloys exhibited significantly lower magnetic susceptibility than medical Ti alloys. The ZNT alloys showed a cell viability of more than 94 % toward MG-63 cells after culturing for 3 d Overall, the spinodal ZNT 15 showed the best combination of mechanical properties, wear resistance, corrosion resistance, low magnetic susceptibility, and sufficient biocompatibility among the three alloys. STATEMENT OF SIGNIFICANCE: This work reports on medium-entropy Zr-Nb-Ti (ZNT) alloys with heterostructure. Spinodal decomposition significantly improved their mechanical strength and reduced the elastic modulus of the alloys. The wear resistance of the ZNT alloys decreased with an increase in Ti content. Dense ZrO 2 , Nb 2 O 5 , and TiO 2 oxide layers were formed during the polarization process in Hanks' solution, which enhanced the corrosion resistance of the alloys. The ZNT alloys exhibited significantly lower magnetic susceptibility than medical Ti alloys. The ZNT alloys showed a cell viability of >94 % toward MG-63 cells after culturing for 3 d The results demonstrate that spinodal ZNT alloys have enormous potential as bone-implant materials due to their outstanding overall mechanical properties, high corrosion resistance, wear resistance, low magnetic susceptibility, and sufficient biocompatibility., Competing Interests: Declaration of competing interests The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Iron-selenium (Fe-Se) alloys have potential as attractive biodegradable bone-implant materials, given the antitumor properties of Se in cancer prevention and therapy. However, the fabrication of Fe-Se alloys is challenging due to the volatility of elemental Se and the significantly different melting points of Se and Fe. In this study, we successfully fabricated Fe-xSe (x = 0.2, 0.4, 0.6, 0.8, and 1 wt.%) alloys using suction casting, with FeSe compounds as the Se source. The microstructures, tensile properties, corrosion behavior, biocompatibility, antibacterial ability, and antitumor properties of the Fe-Se alloys were evaluated. The microstructures of the Fe-Se alloys were composed of α-Fe and FeSe phases. Among the Fe-Se alloys, Fe-0.6Se showed the best combination of tensile properties, with a yield strength of 1096.5 ± 7.2 MPa, an ultimate tensile strength of 1271.6 ± 6.3 MPa, and a fracture strain of 15.6 ± 3.3 %, and a degradation rate of 56.9 ± 0.4 μm/year. Moreover, the Fe-0.6Se alloy showed superb antibacterial ability against S. aureus, antitumor activity against 143B osteosarcoma cells, and osteogenicity and biocompatibility toward pre-osteoblast MC3T3-E1 cells. In summary, adding 0.2-1.0 wt.% Se to Fe does not affect the growth of healthy cells but effectively inhibits the growth and reproduction of tumor cells, and the Fe-0.6Se alloy is promising for orthopedic applications owing to its unique combination of mechanical and biofunctional properties. STATEMENT OF SIGNIFICANCE: This work reports on Fe-xSe (x = 0.2, 0.4, 0.6, 0.8, and 1 wt.%) alloys fabricated using suction casting. The microstructures of the Fe-Se alloys were composed of α-Fe and FeSe phases. Among the Fe-Se alloys, the Fe-0.6Se showed the best combination of tensile properties, with a yield strength of 1058.6 ± 3.9 MPa, an ultimate tensile strength of 1134.1 ± 2.9 MPa, and a fracture strain of 16.8 ± 1.5 %, and a degradation rate of 56.9 ± 0.4 μm/year. Moreover, the Fe-0.6Se alloy showed superb antibacterial ability against S. aureus, antitumor activity against 143B osteosarcoma cells, and significant osteogenic ability and biocompatibility toward pre-osteoblast MC3T3-E1 cells. In summary, the Fe-0.6Se alloy is promising for orthopedic applications owing to its unique combination of mechanical and biofunctional properties., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. The author is an Editorial Board Member/Editor-in-Chief/Associate Editor/Guest Editor for [Journal name] and was not involved in the editorial review or the decision to publish this article., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Guided bone-regeneration membrane (GBRM) is commonly used in bone-repair surgery because it blocks fibroblast proliferation and provides spatial support in bone-defect spaces. However, the need for removal surgery and the lack of antibacterial properties of conventional GBRM limit its therapeutic applicability for alveolar bone defects. Here we developed a GBRM for alveolar bone-repair and -regeneration applications through double-sided electrospinning of polycaprolactone and chitosan layers on a Zn mesh surface (denoted DSZM). The DSZM showed a UTS of ∼25.6 MPa, elongation of ∼16.1%, strength-elongation product of ∼0.413 GPa%, and ultrahigh spatial maintenance ability, and the UTS was over 6 times higher than that of commercial Bio-Gide membrane. The DSZM exhibited a corrosion rate of ∼17 µm/y and a Zn ion concentration of ∼0.23 µg/ml after 1 month of immersion in Hanks' solution. The DSZM showed direct and indirect cytocompatibility with exceptional osteogenic differentiation and calcium deposition toward MC3T3-E1 cells. Further, the DSZM showed strongly sustained antibacterial activity against S. aureus and osteogenesis in a rat critical-sized maxillary defect model. Overall, the DSZM fits the requirements for alveolar bone-repair and -regeneration applications as a biodegradable GBRM material due to its spatial support, suitable degradability, cytocompatibility, and antibacterial and osteogenic capabilities. STATEMENT OF SIGNIFICANCE: This work reports the mechanical properties, antibacterial ability and osteogenic properties of electrospun PCL-CS nanofiber on Zn mesh as biodegradable guided bone-regeneration membrane for alveolar bone-repair applications. Our findings demonstrate that the DSZM prepared by double-sided electrospinning of PCL-CS layers on Zn mesh showed a UTS of ∼25.6 MPa, elongation of ∼16.1%, strength-elongation product of ∼0.413 GPa%, and ultrahigh spatial maintenance ability, and the UTS was over 6 times greater than that of commercial Bio-Gide® membrane. The DSZM showed direct and indirect cytocompatibility with exceptional osteogenic differentiation and calcium deposition toward MC3T3-E1 cells. Further, the DSZM showed strongly sustained antibacterial activity against S. aureus and osteogenesis in a rat critical-sized maxillary defect model., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Biodegradable Zn alloys have significant application potential for hard-tissue implantation devices owing to their suitable degradation behavior and favorable biocompatibility. Nonetheless, pure Zn and its alloys in the as-cast state are mechanically instable and low in strength, which restricts their clinical applicability. Here, we report the exceptional mechanical, corrosion, and biocompatibility properties of hot-extruded Zn-5RE (wt.%, RE = rare earth of Y; or Ho; or Er) alloys intended for use in biodegradable bone substitutes. The microstructural characteristics, mechanical behavior, corrosion resistance, cytocompatibility, osteogenic differentiation, and capacity of osteogenesis in vivo of the Zn-5RE alloys are comparatively investigated. The Zn-5Y alloy demonstrates the best tensile properties, encompassing a 138 MPa tensile yield strength, a 302 MPa ultimate tensile strength, and 63% elongation, while the Zn-5Ho alloy shows the highest compression yield strength of 260 MPa and Vickers hardness of 104 HV. The Zn-5Er alloy shows a 126 MPa tensile yield strength, a 279 MPa ultimate tensile strength, 52% elongation, a 196 MPa compression yield strength, and a 101 HV Vickers microhardness. Further, the Zn-5Er alloy has a 130 µm per year corrosion rate in electrochemical tests and a 26 µm per year degradation rate in immersion tests, which is the lowest among the tested alloys. It also has the best in vitro osteogenic differentiation ability and capacity for osteogenesis and osteointegration in vivo after implantation in rat femurs among the Zn-5RE alloys, indicating promising potential in load-bearing biodegradable internal bone-fixation applications. STATEMENT OF SIGNIFICANCE: This work reports the exceptional mechanical, corrosion, and biocompatibility properties of hot-extruded (HE) Zn-5 wt.%-rare earth (Zn-5RE) alloys using single yttrium (Y), holmium (Ho), and erbium (Er) alloying for biodegradable bone-implant applications. Our findings demonstrate that the HE Zn-5Er alloy showed σ uts of 279 MPa, tensile yield strength of 126 MPa, elongation of 51.6%, compression yield strength of 196 MPa, and microhardness of 101.2 HV. Further, HE Zn-5Er showed the lowest electrochemical corrosion rate of 130 µm/y and lowest degradation rate of 26 µm/y, and the highest in vitro osteogenic differentiation ability, in vivo osteogenesis, and osteointegration ability after implantation in rat femurs among the Zn-5RE alloys, indicating promising potential in load-bearing biodegradable internal bone-fixation applications., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Metallic biomaterials, such as stainless steels, cobalt-chromium-molybdenum (Co-Cr-Mo) alloys, and titanium (Ti) alloys, have long been used as load-bearing implant materials due to their metallic mechanical strength, corrosion resistance, and biocompatibility. However, their magnetic susceptibility and elastic modulus of more than 100 GPa significantly restrict their therapeutic applicability. In this study, spinodal Zr 60 Nb 40 , Zr 50 Nb 50 , and Zr 40 Nb 60 (at.%) alloys were selected from the miscibility gap based on the Zr-Nb binary phase diagram and prepared by casting, cold rolling, and aging. Their microstructure, mechanical properties, corrosion resistance, magnetic susceptibility, and biocompatibility were systematically evaluated. Spinodal decomposition to alternating nanoscale Zr-rich β 1 and Nb-rich β 2 phases occurred in the cold-rolled Zr-Nb alloys during aging treatment at 650 °C. In addition, a minor amount of α phase was precipitated in Zr 60 Nb 40 due to the thermodynamic instability of the Zr-rich β 1 phase. Spinodal decomposition significantly improved the mechanical strength of the alloys due to nanosized dual-cubic reinforcement. The Zr-Nb alloys showed an electrochemical corrosion rate of 94-262 nm per year in Hanks' solution because of formation of dense passive films composed of ZrO 2 and Nb 2 O 5 during the polarization process. The magnetic susceptibilities of the Zr-Nb alloys were significantly lower than those of commercial Co-Cr-Mo and Ti alloys. The cell viability of the Zr-Nb alloys was more than 98 % toward MC3T3-E1 cells. Overall, the spinodal Zr-Nb alloys have enormous potential as bone-implant materials due to their outstanding overall mechanical properties, extraordinary corrosion resistance, low magnetic susceptibility, and sufficient bicompatibility. STATEMENT OF SIGNIFICANCE: This work reports on spinodal Zr-Nb alloys with heterostructure. Spinodal decomposition significantly improved their mechanical strength due to the nanosized dual-cubic reinforcement. The Zr-Nb alloys showed large corrosion resistance in Hanks' solution because of formation of dense passivation films composed of ZrO 2 and Nb 2 O 5 during the polarization process. The magnetic susceptibilities of the Zr-Nb alloys were significantly lower than those of commercial Co-Cr-Mo and Ti alloys. The cell viability of the Zr-Nb alloys was more than 98 % toward MC3T3-E1 cells. The results demonstrate that spinodal Zr-Nb alloys have enormous potential as bone-implant materials due to their outstanding overall mechanical properties, high corrosion resistance, low magnetic susceptibility, and sufficient biocompatibility., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Magnesium (Mg) alloys are widely used in bone fixation and bone repair as biodegradable bone-implant materials. However, their clinical application is limited due to their fast corrosion rate and poor mechanical stability. Here, the development of Mg-2Zn-0.5Ca-0.5Sr (MZCS) and Mg-2Zn-0.5Ca-0.5Zr (MZCZ) alloys with improved mechanical properties, corrosion resistance, cytocompatibility, osteogenesis performance, and antibacterial capability is reported. The hot-extruded (HE) MZCZ sample exhibits the highest ultimate tensile strength of 255.8 ± 2.4 MPa and the highest yield strength of 208.4 ± 2.8 MPa and an elongation of 15.7 ± 0.5%. The HE MZCS sample shows the highest corrosion resistance, with the lowest corrosion current density of 0.2 ± 0.1 µA cm -2 and the lowest corrosion rate of 4 ± 2 µm per year obtained from electrochemical testing, and a degradation rate of 368 µm per year and hydrogen evolution rate of 0.83 ± 0.03 mL cm -2 per day obtained from immersion testing. The MZCZ sample shows the highest cell viability in relation to MC3T3-E1 cells among all alloy extracts, indicating good cytocompatibility except at 25% concentration. Furthermore, the MZCZ alloy shows good antibacterial capability against Staphylococcus aureus., (© 2024 The Authors. Advanced Healthcare Materials published by Wiley‐VCH GmbH.)

Zinc (Zn)-dysprosium (Dy) binary alloys are promising biodegradable bone fracture fixation implants owing to their attractive biodegradability and mechanical properties. However, their clinical application is a challenge for bone fracture healing, due to the lack of Zn-Dy alloys with tailored proper bio-mechanical and osteointegration properties for bone regeneration. A Zn-5Dy alloy with high strength and ductility and a degradation rate aligned with the bone remodeling cycle is developed. Here, mechanical stability is further confirmed, proving that Zn-5Dy alloy can resist aging in the degradation process, thus meeting the mechanical requirements of fracture fixation. In vitro cellular experiments reveal that the Zn-5Dy alloy enhances osteogenesis and angiogenesis by elevating SIRT4-mediated mitochondrial function. In vivo Micro-CT, SEM-EDS, and immunohistochemistry analyses further indicate good biosafety, suitable biodegradation rate, and great osteointegration of Zn-5Dy alloy during bone healing, which also depends on the upregulation of SIRT4-mediated mitochondrial events. Overall, the study is the first to report a Zn-5Dy alloy that exerts remarkable osteointegration properties and has a strong potential to promote bone healing. Furthermore, the results highlight the importance of mitochondrial modulation and shall guide the future development of mitochondria-targeting materials in enhancing bone fracture healing., (© 2024 The Authors. Advanced Science published by Wiley‐VCH GmbH.)

Zinc (Zn) and some of its alloys are recognized as promising biodegradable implant materials due to their acceptable biocompatibility, facile processability, and moderate degradation rate. Nevertheless, the limited mechanical properties and stability of as-cast Zn alloys hinder their clinical application. In this work, hot-rolled (HR) and hot-extruded (HE) Zn-5 wt.% gadolinium (Zn-5Gd) samples were prepared by casting and respectively combining with hot rolling and hot extrusion for bone-implant applications. Their microstructure evolution, mechanical properties, corrosion behavior, cytotoxicity, antibacterial ability, and in vitro and in vivo osteogenesis were systematically evaluated. The HR and HE Zn-5Gd exhibited significantly improved mechanical properties compared with those of their pure Zn counterparts and the HR Zn-5Gd showed a unique combination of tensile properties with an ultimate tensile strength of ∼311.6 MPa, yield strength of ∼236.5 MPa, and elongation of ∼40.6%, all of which are greater than the mechanical properties required for bone-implant materials. The HR and HE Zn-5Gd showed higher corrosion resistance than their pure Zn counterpart in Hanks' solution and the HE Zn-5Gd had the lowest corrosion rate of 155 µm/y measured by electrochemical corrosion and degradation rate of 26.9 µm/y measured by immersion testing. The HR and HE Zn-5Gd showed high cytocompatibility toward MC3T3-E1 and MG-63 cells, high antibacterial effects against S. aureus, and better in vitro osteogenic activity than their pure Zn counterparts. Furthermore, the HE Zn-5Gd exhibited better in vivo biocompatibility, osteogenesis, and osteointegration ability than pure Zn and pure Ti. STATEMENT OF SIGNIFICANCE: This work reports the mechanical properties, corrosion behaviors, cytocompatibility, antibacterial ability, in vitro and in vivo osteogenesis of biodegradable Zn-Gd alloy for bone-implant applications. Our findings demonstrate that the hot-rolled (HR) Zn-5Gd showed a unique combination of tensile properties with an ultimate tensile strength of ∼311.6 MPa, yield strength of ∼236.5 MPa, and elongation of ∼40.6%. The HR and HE Zn-5Gd showed higher corrosion resistance than their pure Zn counterpart in Hanks' solution. The HR and HE Zn-5Gd showed high cytocompatibility toward MC3T3-E1 and MG-63 cells, good antibacterial effects against S. aureus, and better in vitro osteogenic activity. Furthermore, the HE Zn-5Gd exhibited better in vivo biocompatibility, osteogenesis, and osteointegration ability than pure Zn and pure Ti., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Zinc (Zn), magnesium (Mg), and their respective alloys have attracted great attention as biodegradable bone-implant materials due to their excellent biocompatibility and biodegradability. However, the poor mechanical strength of Zn alloys and the rapid degradation rate of Mg alloys limit their clinical application. The manufacture of Zn and Mg bimetals may be a promising way to improve their mechanical and degradation properties. Here we report on Zn/Mg multilayered composites prepared via an accumulative roll bonding (ARB) process. With an increase in the number of ARB cycles, the thicknesses of the Zn layer and the Mg layer were reduced, while a large number of heterogeneous interfaces were introduced into the Zn/Mg multilayered composites. The composite samples after 14 ARB cycles showed the highest yield strength of 411±3 MPa and highest ultimate tensile strength of 501±3 MPa among all the ARB processed samples, significantly higher than those of the Zn/Zn and Mg/Mg multilayered samples. The Zn and Mg layers remained continuous in the Zn/Mg composite samples after annealing at 150 °C for 10 min, resulting in a decrease in yield strength from 411±3 MPa to 349±3 MPa but an increase in elongation from 8±1% to 28±1%. The degradation rate of the Zn/Mg multilayered composite samples in Hanks' solution was ranged from 127±18 µm/y to 6±1 µm/y. The Zn/Mg multilayered composites showed over 100% cell viability with their 25% and 12.5% extracts in relation to MG-63 cells after culturing for 3 d, indicating excellent cytocompatibility. STATEMENT OF SIGNIFICANCE: This work reports a biodegradable Zn/Mg multilayered composite prepared by accumulative roll bonding (ARB) process. The yield and ultimate tensile strength of the Zn/Mg multilayered composites were improved due to grain refinement and the introduction of a large number of heterogeneous interfaces. The composite samples after 14 ARB cycles showed the highest yield strength of 411±3 MPa and highest ultimate tensile strength of 501±3 MPa among all the ARB processed samples. The degradation rate of the Zn/Mg multilayered composite meets the required degradation rate for biodegradable bone-implant materials. The results demonstrated that it is a very promising approach to improve the strength and biocompatibility of biodegradable Zn-based alloys., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

Zinc (Zn) and its alloys are used in bone-fixation devices as biodegradable bone-implant materials due to their good biosafety, biological function, biodegradability, and formability. Unfortunately, the clinical application of pure Zn is hindered by its insufficient mechanical properties and slow degradation rate. In this study, a Zn-5 wt.% lanthanum (Zn-5La) alloy with enhanced mechanical properties, suitable degradation rate, and cytocompatibility was developed through La alloying and hot extrusion. The hot-extruded (HE) Zn-5La alloy showed ultimate tensile strength of 286.3 MPa, tensile yield strength of 139.7 MPa, elongation of 35.7%, compressive yield strength of 262.7 MPa, and microhardness of 109.7 HV. The corrosion resistance of the HE Zn-5La in Hanks' and Dulbecco's modified Eagle medium (DMEM) solutions gradually increased with prolonged immersion time. Further, the HE Zn-5La exhibited an electrochemical corrosion rate of 36.7 μm/y in Hanks' solution and 11.4 μm/y in DMEM solution, and a degradation rate of 49.5 μm/y in Hanks' solution and 30.3 μm/y in DMEM solution, after 30 d of immersion. The corrosion resistance of both HE Zn and Zn-5La in DMEM solution was higher than in Hanks' solution. The 25% concentration extract of the HE Zn-5La showed a cell viability of 106.5%, indicating no cytotoxicity toward MG-63 cells. We recommend the HE Zn-5La alloy as a promising candidate material for biodegradable bone-implant applications. STATEMENT OF SIGNIFICANCE: This work reports the mechanical properties, corrosion and degradation behaviors, in vitro cytocompatibility and antibacterial ability of biodegradable Zn-5La alloy for bone-implant applications. Our findings demonstrate that the hot-extruded (HE) Zn-5La alloy showed an ultimate tensile strength of 286.3 MPa, a yield strength of 139.7 MPa, an elongation of 35.7%, compressive yield strength of 262.7 MPa, and microhardness of 109.7 HV. HE Zn-5La exhibited appropriate degradation rates in Hanks' and DMEM solutions. Furthermore, the HE Zn-5La alloy showed good cytocompatibility toward MG-63 and MC3T3-E1 cells and greater antibacterial ability against S. aureus., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Owing to its superior mechanical and biological properties, titanium metal is widely used in dental implants, orthopedic devices, and bone regenerative materials. Advances in 3D printing technology have led to more and more metal-based scaffolds being used in orthopedic applications. Microcomputed tomography (μCT) is commonly applied to evaluate the newly formed bone tissues and scaffold integration in animal studies. However, the presence of metal artifacts dramatically hinders the accuracy of μCT analysis of new bone formation. To acquire reliable and accurate μCT results that reflect new bone formation in vivo , it is crucial to lessen the impact of metal artifacts. Herein, an optimized procedure for calibrating μCT parameters using histological data was developed. In this study, the porous titanium scaffolds were fabricated by powder bed fusion based on computer-aided design. These scaffolds were implanted in femur defects created in New Zealand rabbits. After 8 weeks, tissue samples were collected to assess new bone formation using μCT analysis. Resin-embedded tissue sections were then used for further histological analysis. A series of deartifact two-dimensional (2D) μCT images were obtained by setting the erosion radius and the dilation radius in the μCT analysis software (CTan) separately. To get the μCT results closer to the real value, the 2D μCT images and corresponding parameters were subsequently selected by matching the histological images in the particular region. After applying the optimized parameters, more accurate 3D images and more realistic statistical data were obtained. The results demonstrate that the newly established method of adjusting μCT parameters can effectively reduce the influence of metal artifacts on data analysis to some extent. For further validation, other metal materials should be analyzed using the process established in this study.

Zinc (Zn)-based alloys and composites are gaining increasing interest as promising biodegradable implant materials due to their appropriate biodegradation rates and biological functionalities. However, the inadequate mechanical strength and ductility of pure Zn have restricted its application. In this study, Zn matrix composites (ZMCs) reinforced with 0.1-0.4 wt.% graphene nanoplatelets (GNP) fabricated via powder metallurgy were investigated as potential biodegradable implant materials. The microstructures, mechanical properties, and corrosion behaviors of the GNP-reinforced ZMCs were characterized using optical microscopy, scanning electron microscopy combined with energy-dispersive X-ray spectroscopy, Raman spectroscopy, compression testing, and electrochemical and immersion testing in Hanks' balanced salt solution (HBSS). The microstructural study revealed that the GNP was uniformly dispersed in the ZMCs after ball milling and sintering at 420°C for 6 h. The microhardness, compressive yield strength, ultimate compressive strength, and compressive strain of the ZMC-0.2GNP were 69 HV, 123 MPa, 247 MPa, and 23 %, respectively, improvements of ∼ 18 %, 50%, ∼ 28%, and ∼ 15% compared to pure Zn. The corrosion rate of the ZMCs were lower than that of the pure Zn in HBSS, and the ZMC-0.2GNP composite exhibited the lowest corrosion rate of 0.09 mm/y as measured by electrochemical testing. Biocompatibility assessment indicated that the diluted extracts of pure Zn and GNP-reinforced ZMCs with concentrations of 12.5% and 6.25% exhibited no cytotoxicity after cell culturing for up to 5 days, and the diluted extracts of ZMC-0.2 GNP composite revealed more than 90% cell viability after cell culturing of 3 days, showing the satisfying cytocompatibility. STATEMENT OF SIGNIFICANCE: Biodegradable Zn is a promising candidate material for orthopedic implant applications. Nonetheless, the inadequate mechanical strength and ductility of pure Zn limited its clinical application. In this study, Zn matrix composites (ZMCs) reinforced with 0.1-0.4 wt.% graphene nanoplatelets (GNP) were developed via powder metallurgy, and the reinforcing efficacy of GNP on their mechanical properties was investigated. The addition of GNP significantly improved the compressive properties of ZMCs, with the Zn-0.2GNP composite exhibiting the best compressive properties, including 123 MPa compressive yield strength, 247 MPa ultimate compressive strength, and 22.9% compressive strain. Further, the 12.5% concentration extract of the ZMCs exhibited no cytotoxicity after cell culturing for 5 d toward SaOS2 cells., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022. Published by Elsevier Ltd.)

The unique combination of biodegradability, biocompatibility, and functionality of zinc (Zn)-based alloys makes them highly desirable for a wide range of medical applications. However, a long-standing problem associated with this family of biodegradable alloys in the as-cast state is their limited mechanical strength and slow degradation rate. Here we report the development of Zn-xDy (x = 1, 3, and 5 wt.%) alloys with high strength, ductility, cytocompatibility, antibacterial ability, and appropriate degradation rate for biodegradable bone-implant applications. Our results indicate that the mechanical properties of Zn-xDy alloys were effectively improved with increasing Dy addition and hot-rolling due to the second-phase strengthening. The hot-rolled (HR) Zn-3Dy alloy showed the best combined mechanical performance with an ultimate tensile strength of 270.5 MPa, a yield strength of 214.8 MPa, an elongation of 55.1%, and Brinell hardness of 75.9 HB. The corrosion and degradation rates of HR Zn-xDy alloys in Hanks' solution gradually increased with increasing Dy addition due to the intensification of galvanic corrosion. The HR Zn-3Dy alloy showed high antibacterial ability against S. aureus and cytocompatibility toward MC3T3-E1 cells among all the HR alloys. Overall, the HR Zn-3Dy alloy can be considered a promising biodegradable material for bone implants. STATEMENT OF SIGNIFICANCE: This work reports on Zn-xDy (x = 1, 3, and 5%) alloys fabricated by Dy alloying followed by hot-rolling for biodegradable bone-implant applications. Our findings demonstrate that the hot-rolled (HR) Zn-3Dy alloy showed the best combined mechanical performance with an ultimate tensile strength of 270.5 MPa, a yield strength of 214.8 MPa, an elongation of 55.1%, and Brinell hardness of 75.9 HB. The corrosion and degradation rates of HR Zn-xDy alloys in Hanks' solution gradually increased with increasing Dy addition due to the intensification of galvanic corrosion. Furthermore, the HR Zn-3Dy alloy showed greater antibacterial ability against S. aureus and the best cytocompatibility toward MC3T3-E1 cells among all the HR alloys., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022. Published by Elsevier Ltd.)

This study systematically investigated the effect of equal channel angular pressing (ECAP) on the microstructure, mechanical, corrosion, nano-tribological properties and biocompatibility of a newly developed β Ti-28Nb-35.4Zr (hereafter denoted TNZ) alloy. Results indicated that ECAP of the β TNZ alloy refined its microstructure by forming ultrafine grains without causing stress-induced phase transformation, leading to formation of a single β phase. The ECAP-processed TNZ alloy exhibited a compressive yield strength of 960 MPa, and high plastic deformation capacity without fracturing under compression loads. Potentiodynamic polarization tests revealed the higher tendency of ECAP-processed TNZ alloys to form passive oxide films on its surface, which exhibited a lower corrosion rate (0.44±0.07 µm/y) in Hanks' balanced salt solution compared to its as-cast counterpart (0.71±0.10 µm/y). Nanotribological testing also revealed higher resistance of the ECAP-processed TNZ alloy to abrasion, wear and scratching, when compared to its as-cast counterpart. Cytocompatibility and cell adhesion assessments of the ECAP-processed TNZ alloys showed a high viability (111%) of human osteoblast-like SaOS2 cells after 7 d of culturing. Moreover, the ECAP-processed TNZ alloy promoted adhesion and spreading of SaOS2 cells, which exhibited growth and proliferation on alloy surfaces. In summary, significantly enhanced mechanical, corrosion, and biological properties of ECAP-processed TNZ alloy advocate its suitability for load-bearing implant applications. STATEMENT OF SIGNIFICANCE: Equal channel angular pressing (ECAP) provides a unique combination of enhanced mechanical and functional properties of materials by optimizing their microstructures and phase transformations. This study investigated the mechanical, nano-tribological, corrosion, and biocompatibility properties of a newly developed β Ti-28Nb-35.4Zr (TNZ) alloy processed via ECAP. Our findings indicated that ECAP of the β TNZ alloy refined its microstructure by forming ultrafine grains without causing stress-induced phase transformation. Compared to its as-cast counterpart, ECAP-processed TNZ exhibited significantly enhanced compressive yield strength, plastic deformation capacity, hardness, wear, and corrosion properties. Moreover, in vitro cytocompatibility and cell adhesion studies revealed high cellular viabilities, growth and proliferation of osteoblast-like SaOS2 cells on the ECAP-processed TNZ alloy., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2022. Published by Elsevier Ltd.)

Zinc (Zn)-based composites have received extensive attention as promising biodegradable materials due to their unique combination of moderate biodegradability, biocompatibility, and functionality. Nevertheless, the low mechanical strength of as-cast Zn-based composites impedes their practical clinical application. Here we reported the mechanical properties, corrosion behavior, wear properties, and cytotoxicity of in situ synthesized biodegradable Zn-xMg 2 Ge (x = 1, 3, and 5 wt.%) composites for bone-implant applications. The mechanical properties of Zn-xMg 2 Ge composites were effectively improved by alloying and hot-rolling due to particle reinforcement of the Mg 2 Ge intermetallic phase and dynamic recrystallization. The hot-rolled (HR) Zn-3Mg 2 Ge composite exhibited the best mechanical properties, including a yield strength of 162.3 MPa, an ultimate tensile strength of 264.3 MPa, an elongation of 10.9%, and a Brinell hardness of 83.9 HB. With an increase in Mg 2 Ge content, the corrosion and degradation rates of the HR Zn-xMg 2 Ge composites gradually increased, while their wear rate decreased and then increased in Hanks' solution. The diluted extract (12.5% concentration) of the HR Zn-3Mg 2 Ge composite showed the highest cell viability compared to the other HR composites and their as-cast pure Zn counterparts. Overall, the HR Zn-3Mg 2 Ge composite can be considered a promising biodegradable Zn-based composite for bone-implant applications. STATEMENT OF SIGNIFICANCE: This paper reports the mechanical properties, corrosion behavior, wear properties, and cytotoxicity of in situ synthesized biodegradable Zn-xMg 2 Ge (x = 1, 3, and 5 wt.%) composites for bone-implant applications. Our findings demonstrated that the mechanical properties of Zn-xMg 2 Ge composites were effectively improved by alloying and hot-rolling due to Mg 2 Ge particle reinforcement and dynamic recrystallization. The hot-rolled Zn-3Mg 2 Ge composite showed superior cytocompatibility, satisfying corrosion and degradation rates, and the best mechanical properties including a yield strength of 162.3 MPa, an ultimate tensile strength of 264.3 MPa, and an elongation of 10.9%., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

Zinc (Zn)-based metals and alloys are emerging as promising biodegradable implant materials due to their inherent biodegradability and good biocompatibility. However, this class of materials exhibits low mechanical strength and a slow degradation rate, which hinders their clinical application. Here we report the development of a new biodegradable Fe/Zn-3Cu composite fabricated by infiltration casting of a Zn-3Cu alloy into an Fe foam followed by hot-rolling. Our results indicate that the hot-rolled (HR) Fe/Zn-3Cu composite exhibited an α-Zn matrix phase, a secondary CuZn 5 phase, and an α-Fe phase. The HR Fe/Zn-3Cu composite exhibited an ultimate tensile strength of 269 MPa, a tensile yield strength of 210 MPa, and an elongation of 27%. The HR Fe/Zn-3Cu composite showed a degradation rate of 228 µm/year after immersion in Hanks' solution for 30 d The diluted extract of the HR Fe/Zn-3Cu composite exhibited a higher cell viability than that of the HR Zn-3Cu alloy in relation to MC3T3-E1 and MG-63 cells. Furthermore, the HR Fe/Zn-3Cu composite showed significantly better antibacterial ability than that of the HR Zn-3Cu alloy in relation to S. aureus. Overall, the HR Fe/Zn-3Cu composite can be anticipated to be a promising biodegradable implant material for bone-fixation applications. STATEMENT OF SIGNIFICANCE: This work reports a new biodegradable Fe/Zn-3Cu composite fabricated by infiltration casting and followed by hot-rolling for biodegradable bone-fixation application. Our findings demonstrated that the hot-rolled (HR) Fe/Zn-3Cu composite exhibited an ultimate tensile strength of 269.1 MPa, a tensile yield strength of 210.3 MPa, and an elongation of 26.7%. HR Fe/Zn-3Cu composite showed a degradation rate of 227.6 µm/a, higher than HR Zn-3Cu alloy after immersion in Hanks' solution for 30 d The diluted extracts of the HR Fe/Zn-3Cu composite exhibited a higher cell viability than HR Zn-3Cu alloy toward MC3T3-E1 cells. Furthermore, the HR Fe/Zn-3Cu composite showed significantly better antibacterial ability than the HR Zn-3Cu alloy toward S. aureus., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022. Published by Elsevier Ltd.)

Zinc (Zn) and its alloys are currently regarded as one of the promising families of biodegradable metals for implant applications owing to their suitable biodegradability and biofunctionality. However, the inadequate mechanical properties of as-cast (AC) pure Zn restricted the practical clinical bone-implant applications due to its coarse grain size and hexagon close-packed crystal structure. Here, the impact of gadolinium (Gd) on the mechanical properties, corrosion resistance, hemolysis percentage, anticoagulant activity, and cytotoxicity of AC and hot-rolled (HR) Zn-1Mg-xGd (x = 0.1, 0.2, and 0.3) (wt.%) alloys were investigated for biodegradable bone-implant applications. Tensile testing showed that the HR Zn-1Mg-0.3Gd alloy exhibited the highest tensile strength of 288.1 MPa, tensile yield strength of 250.9 MPa, and elongation of 13.2%. Electrochemical corrosion and immersion tests revealed that the corrosion rates of both AC and HR specimens increased with increasing Gd content in Hanks' solution, and the HR Zn-1Mg-xGd specimens exhibited higher corrosion rates compared to their AC counterparts. The HR Zn-1Mg-xGd specimens showed an increasing hemolysis percentages and decreasing activated partial thromboplastin time (APTT) values with increasing Gd addition. The alloy extracts of HR samples at ≤ 25% concentration exhibited no cytotoxicity toward MG-63 cells, and the HR Zn-1Mg-0.3Gd alloy displayed the highest cell viability among all three alloy extracts at 12.5% concentration. Overall, the HR Zn-1Mg-0.3Gd can be considered a promising biodegradable implant material for bone-implant materials owing to its high mechanical strength and ductility, suitable degradation rate, and satisfying biocompatibility. STATEMENT OF SIGNIFICANCE: In this work, Zn-1Mg-xGd (x = 0.1, 0.2, and 0.3 wt.%) alloys were developed by alloying with gadolinium (Gd) and hot-rolling, and their mechanical properties, corrosion behavior, hemolysis percentage, anticoagulant activity, and cytotoxicity were investigated for biodegradable implant application. Our findings demonstrated that the hot-rolled Zn-1Mg-0.3Gd alloy exhibit the highest ultimate tensile strength of 288.1 MPa, yield strength of 250.9 MPa, and elongation of 13.2%. Hot-rolled Zn-1Mg-xGd alloys show slowly increasing hemolysis percentages and decreasing activated partial thromboplastin time (APTT) values with increasing Gd addition. Extracts of hot-rolled Zn-1Mg-xGd alloys at a concentration of ≤ 25% show no cytotoxicity towards MG-63 cells, and Zn-1Mg-0.3Gd exhibit good cytocompatibility among all three alloys at a concentration of 12.5%., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022. Published by Elsevier Ltd.)

Magnesium (Mg) and some of its alloys are considered promising biodegradable metallic biomaterials for bone implant applications. The osteogenesis effect of Mg alloys is widely reported; however, the underlying mechanisms are still not clear. In this study, pure Mg, Mg-3Zn, and Mg-2Zn-1Mn were prepared, and their degradation behavior, biocompatibility, and osteogenesis effect were systematically assessed both in vitro and in vivo. Primary rat bone marrow-derived mesenchymal stem cells (BMSCs) were used to evaluate the biocompatibility of the prepared Mg alloys, and a rat femur fracture model was used to assess the stimulating effect of these alloys on bone-tissue formation. Mg-2Zn-1Mn showed higher corrosion resistance and more stable degradation behavior than pure Mg and Mg-3Zn. Extracts of the three materials showed significant stimulating effects on osteogenic differentiation of BMSCs along with non-cytotoxicity. Implantation of Mg-2Zn-1Mn wires into the femur of rats demonstrated superior histocompatibility, stable degradation, and notable promotion of osteogenesis without systemic toxicity. Moreover, the results of both in vitro and in vivo assessments demonstrated that bone morphogenetic proteins and fibroblast growth factor receptors are involved in the stimulating effect of Mg alloys. STATEMENT OF SIGNIFICANCE: This work reports the degradation behavior, biocompatibility, and osteogenic effect of pure Mg and Mg-3Zn and Mg-2Zn-1Mn alloys in both in vitro and in vivo conditions. Mg-2Zn-1Mn showed higher corrosion resistance and more stable degradation behavior than pure Mg and Mg-3Zn. The extracts of the three materials showed a significant stimulating effect on osteogenic differentiation of rat bone marrow-derived mesenchymal stem cells (BMSCs) along with non-cytotoxicity. Mg-2Zn-1Mn wires implanted into the femur of rats showed good histocompatibility, stable degradation, and notable promotion of osteogenesis without systemic toxicity. The results of the present study suggest that bone morphogenetic proteins (BMPs) and fibroblast growth factor receptors (FGFRs) are involved in the stimulating effect of Mg alloys on osteogenesis., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest associated with this article., (Copyright © 2021 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

β-type titanium (Ti) alloys have been extensively investigated as orthopedic implant materials due to their unique combination of low elastic modulus, high specific strength, corrosion resistance, and biocompatibility. In this study the mechanical properties, corrosion behavior, friction and wear performance, and cytotoxicity of β-type Ti-24Nb-38Zr-2Mo (TNZM) and Ti-24Nb-38Zr-2Mo-0.1Sc (TNZMS) have been comparatively investigated for orthopedic applications. Cold-rolling (CR) and cold-rolling plus solution-treatment (CR+ST) were performed on the as-cast (AC) alloys and their microstructures and material properties were characterized. The impact of Sc addition on the mechanical and corrosion properties, friction and wear behavior, and in vitro cytocompatibility of the TNZMS alloy was assessed. The CR+ST TNZMS alloy exhibited the best combination of properties among all the alloy samples, with a yield strength of 780 MPa, ultimate strength of 809 MPa, elongation of 19%, Young's modulus of 65.4 GPa, and hardness of 265 HV. Electrochemical testing in Hanks' Solution indicated that the CR+ST TNZMS sample also showed the highest corrosion resistance with a corrosion potential of -0.234 V, corrosion current density of 0.07 µA/cm 2 , and corrosion rate of 1.2 µm/y. Friction and wear testing revealed that the TNZMS alloy showed higher wear resistance compared to the TNZM alloy and the wear resistance of the different samples was ranked CR > CR+ST > AC. Finally, both the CR+ST TNZM and TNZMS showed no-cytotoxicity towards MG-63 cells and the TNZMS exhibited slightly higher cytocompatibility than the TNZM alloy. STATEMENT OF SIGNIFICANCE: This work reports the β-type Ti-24Nb-38Zr-2Mo (TNZM) and Ti-24Nb-38Zr-2Mo-0.1Sc (TNZMS) alloys fabricated by as-cast (AC), cold-rolling (CR), and cold-rolling plus solution-treatment (CR+ST) for potential orthopedic applications. The experimental results showed that the TNZMS alloy exhibited significantly enhanced mechanical, wear, and corrosion properties than those of TNZM alloy; and the CR+ST TNZMS possess a unique combination of the best mechanical and corrosion properties including a yield strength of 780 MPa, ultimate strength of 809 MPa, elongation of 19%, Young's modulus of 65.4 GPa, and corrosion rate of 1.2 µm/y in Hanks' Solution. Both the CR+ST TNZM and TNZMS alloys exhibited non-cytotoxicity towards MG-63 cells and TNZMS showed a higher cytocompatibility than that of TNZM., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

Magnesium (Mg) is well-tolerated by the body, displaying exceedingly low toxicity, rapid excretion, and numerous bioactive effects, including improved bone formation and protection against oxidative stresses; further, Mg alloys can be degraded in vivo to allow complete removal of an implant without surgical intervention, avoiding revision surgery and thrombosis concerns seen with permanent implants. Rare earth elements (REEs) have been of particular interest in alloying Mg alloys for nearly a century due to their unique chemical and physical properties but have attracted increasing attention in recent decades. The REEs contribute greatly to the mechanical and biological properties of metal alloys, and so are common in Mg alloys in a wide variety of applications; in particular, they represent the dominant alloying additions in current, clinically applied Mg alloys. Notably, the use of these elements may assist in the development of advanced Mg alloys for use as biodegradable orthopedic implants and cardiovascular stents. To this end, current research progress in this area, highlighting the physiological impact of REEs in Mg alloys, is reviewed. Clinical work and preclinical data of REE-containing Mg alloys are analyzed. The biological roles of REEs in cellular responses in vivo require further research in the development of biofunctional Mg alloy medical devices. STATEMENT OF SIGNIFICANCE: The presented work is a review into the biological impact and current application of rare-earth elements (REEs) in biodegradable Mg-based biomaterials. Despite their efficacy in improving corrosion, mechanical, and manufacturability properties of Mg alloys, the physiological effects of REEs remain poorly understood. Therefore, the present work was undertaken to both provide guidance in the development of new biomedical alloys, and highlight areas of existing concerns and unclear knowledge. Key findings of this review include a summary of current clinical and preclinical work, and the identification of Sc as the most promising REE with regards to physiological impact. Y, Ce, Pr, Gd, Dy, Yb, Sm, and Eu should be considered carefully before their use as alloying elements, with other REEs intermediate or insufficiently studied., Competing Interests: Declaration of Competing Interest None., (Copyright © 2021. Published by Elsevier Ltd.)

Hydroxyapatite (HA) coating has received significant attention in the scientific community for the development of implants, and HA coating on titanium oxide (TiO 2 ) nanotubes has shown potential benefits in the improvement of cell proliferation, adhesion, and differentiation. In this study, a HA coating on a TiO 2 nanotubular surface was developed to improve the biocompatibility of the titanium (Ti) surface via magnetron sputtering. Scanning electron microscopy (SEM), surface profilometry, and water contact goniometry revealed that HA-coated TiO 2 nanotubes influenced the surface roughness ( R a ) and hydrophilicity. The XRD and FTIR peaks indicated the presence of crystalline phases of TiO 2 (anatase) and HA-coated TiO 2 nanotubes after annealing at 500 °C for 120 min. The HA-coated TiO 2 nanotubes showed significantly increased R a and decreased water contact angle (θ) compared to the as-anodized TiO 2 nanotubular and bare CP-Ti surfaces. MTS assay using osteoblast-like cells confirmed that the HA-coated TiO 2 nanotubular surface provided an enhanced cell attachment and growth when compared to as-anodized TiO 2 nanotubular and pure CP-Ti surfaces.

Zinc (Zn)-based alloys have been considered potential biodegradable materials for medical applications due to their good biodegradability and biocompatibility. However, the insufficient mechanical properties of pure Zn do not meet the requirements of biodegradable implants. In this study, we have developed a biodegradable Zn-3Mg-0.7Mg 2 Si composite fabricated by high-pressure solidification. Microstructural characterization revealed that the high-pressure solidified (HPS) composite exhibited uniformly distributed fine MgZn 2 granules in an α-Zn matrix. Comprehensive tests indicated that the HPS composite exhibited exceptionally high compression properties including a compressive yield strength of 406.2 MPa, an ultimate compressive strength of 1181.2 MPa, and plastic deformation up to 60% strain without cracking or fracturing. Potentiodynamic polarization tests revealed that the HPS composite showed a corrosion potential of -0.930 V, a corrosion current density of 3.5 μA/cm 2 , and a corrosion rate of 46.2 μm/y. Immersion tests revealed that the degradation rate of the HPS composite after immersion in Hanks' solution for 1 month and 3 months was 42.8 μm/y and 37.8 μm/y, respectively. Furthermore, an extract of the HPS composite exhibited good cytocompatibility compared with as-cast (AC) pure Zn and an AC composite at a concentration of ≤25%. These results suggest that the HPS Zn-3Mg-0.7Mg 2 Si composite can be anticipated as a promising biodegradable material for orthopedic applications., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021. Published by Elsevier Ltd.)

Zinc (Zn) and its alloys are receiving great attention as promising biodegradable materials due to their suitable corrosion resistance, good biocompatibility, and highly desirable biofunctionality. Nevertheless, the low mechanical strength of pure Zn impedes its practical clinical application and there have been calls for further research into the Zn alloys and thermomechanical processes to enhance their mechanical properties and biocompatibility. Here, we report on the alloying efficacy of rare earth elements (REEs) including erbium (Er), dysprosium (Dy), and holmium (Ho) on the microstructure, mechanical properties, corrosion and wear behavior, and in vitro biological properties of Zn-1Mg-0.1RE alloys. Microstructural characterization revealed that the addition of 0.1 wt.% REEs had a significant refining effect on the grain size of the α-Zn matrix and the second phases of the alloys. Alloying of the REEs and hot-rolling effectively improved the mechanical properties due to both precipitation strengthening of the second phases of ErZn 5 , DyZn 5 , and Ho 2 Zn 17 and grain-refinement strengthening. The highest ultimate tensile strength of 259.4 MPa and yield strength of 234.8 MPa with elongation of 16.8% were achieved in the hot-rolled Zn-1Mg-0.1Ho. Alloying of REEs also improved the wear and corrosion resistance, and slowed down the degradation rate in Hanks' solution. Zn-1Mg-0.1Er showed the highest cytocompatibility of MC3T3-E1 cells cultured directly on the alloy surface and of MG-63 cells cultured in the alloy extract. Zn-1Mg-0.1Dy showed the best anticoagulant property among all the alloys. Overall, these Zn-1Mg-0.1RE (Er, Dy, and Ho) alloys can be considered promising biodegradable metallic materials for orthopedic applications., Competing Interests: Declaration of competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020. Published by Elsevier Ltd.)

Biodegradable zinc (Zn) and its alloys have great potential to be used for orthopedic applications due to their suitable degradation rate and good biocompatibility. However, pure Zn has insufficient mechanical properties, such as low strength and hardness, and poor plasticity, which limits its clinical applications. Here, we report on a new series of ternary Zn-3Ge-0.5X (X=Cu, Mg, and Fe) alloys aiming to achieve good corrosion resistance and biocompatibility, and enhanced mechanical properties via micro-alloying with copper (Cu), magnesium (Mg), and iron (Fe). Hot-rolling has also been applied to the new ternary alloys to further enhance their mechanical properties. Mechanical testing results indicate that both the strength and hardness of hot-rolled Zn-3Ge are significantly improved with micro-alloying of Cu, Mg, and Fe; of which the hot-rolled Zn-3Ge-0.5Mg exhibits the highest ultimate tensile strength of 253.4 MPa and yield strength of 208.5 MPa among all the alloys, 25.9% and 44.7% higher than those of the hot-rolled Zn-3Ge. The degradation rate of the as-cast alloys is lower than that of the hot-rolled alloys in Hanks' solution for 1 month and the hot-rolled Zn-3Ge-0.5Mg alloy exhibits the highest degradation rate of 0.075 mm/y. CCK-8 assay using MG-63 cells indicates that the diluted extracts of Zn-3Ge-0.5X (X=Cu, Mg, and Fe) alloys with concentrations of 12.5% and 25% exhibit no or slight cytotoxicity, and the diluted extracts of Zn-3Ge-0.5Cu alloys show high cell viability of over 100%, showing the best cytocompatibility., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020. Published by Elsevier Ltd.)

Biodegradable metals (BMs) gradually degrade in vivo by releasing corrosion products once exposed to the physiological environment in the body. Complete dissolution of biodegradable implants assists tissue healing, with no implant residues in the surrounding tissues. In recent years, three classes of BMs have been extensively investigated, including magnesium (Mg)-based, iron (Fe)-based, and zinc (Zn)-based BMs. Among these three BMs, Mg-based materials have undergone the most clinical trials. However, Mg-based BMs generally exhibit faster degradation rates, which may not match the healing periods for bone tissue, whereas Fe-based BMs exhibit slower and less complete in vivo degradation. Zn-based BMs are now considered a new class of BMs due to their intermediate degradation rates, which fall between those of Mg-based BMs and Fe-based BMs, thus requiring extensive research to validate their suitability for biomedical applications. In the present study, recent research and development on Zn-based BMs are reviewed in conjunction with discussion of their advantages and limitations in relation to existing BMs. The underlying roles of alloy composition, microstructure, and processing technique on the mechanical and corrosion properties of Zn-based BMs are also discussed., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. SWCNT: Single-walled carbon nanotube; MWCNT: Multi-walled carbon nanotube., (© 2020 [The Author/The Authors].)

In this study, porous iron (Fe)-manganese (Mn) alloys with high porosity were successfully prepared by sponge impregnation and sintering (SIS). The compositions of the porous Fe-Mn alloys were strongly dependent on the sintering temperature, and the Mn content was ~44, 30, and 12 wt.% for alloys sintered at 1100, 1150, and 1200 °C, respectively. The porous Fe-Mn alloys exhibited a well-interconnected porous structure with ~85% porosity and average pore size ranging from 375 to 500 um. The porous Fe-44Mn and Fe-30Mn alloys were mainly composed of a γ-austenite phase, while the porous Fe-12Mn was composed of an α-ferrite phase. The yield strength and elastic modulus of the porous Fe-Mn alloys ranged from 6 to 10 MPa and from 0.12 to 0.37 GPa, respectively, similar to those of cancellous bone. The degradation rate of the porous Fe-Mn alloys decreased over time during immersion in simulated body fluid (SBF), and was 1.0 mm/year for Fe-44Mn, 0.81 mm/year for Fe-30Mn, 0.41 mm/year for Fe-12Mn, and 0.33 mm/year for pure Fe after 14 d SBF immersion. Moreover, the porous Fe-Mn alloys exhibited good biocompatibility with clearly enhanced cell proliferation after direct culturing of osteoblastic MC3T3-E1 cells for 7 d. Thus, these porous Fe-Mn alloys can be anticipated to be promising biodegradable implant materials. STATEMENT OF SIGNIFICANCE: This work reports on porous Fe-Mn alloys with high porosity, suitable mechanical properties and degradation rate, and good biocompatibility. The porous alloys prepared by sponge impregnation and sintering exhibited a well-interconnected porous structure with ~85% porosity and average pore size ranging from 375 to 500 um. The yield strength and elastic modulus of the porous alloys ranged from 6 to 10 MPa and from 0.12 to 0.37 GPa, respectively, similar to those of cancellous bone. The degradation rates in simulated body fluid (SBF) were ~1.0 mm/year for Fe-44Mn, 0.81 mm/year for Fe-30Mn, and 0.41 mm/year for Fe-12Mn, respectively. Moreover, the porous Fe-Mn alloys exhibited good biocompatibility with enhanced cell proliferation after direct culturing of osteoblastic MC3T3-E1 cells., Competing Interests: Declaration of Competing Interest We declare that we have no financial and personal relationships with other people or organizations that can inappropriately influence our work, there is no professional or other personal interest of any nature or kind in any product, service and/or company that could be construed as influencing the position presented in, or the review of, the manuscript entitled., (Copyright © 2020. Published by Elsevier Ltd.)

Rare earth elements (REEs) have found application in metallurgical processes for nearly a century due to their unique chemical and physical properties but have gained increased attention in recent decades. Notably, the use of these elements may assist in the development of advanced magnesium and titanium products for applications spanning biomedicine, aerospace, and the automotive industry. To this end, current progress in this area, highlighting work done in Australian research organizations with particular academic expertise, is reviewed. Two areas that require further research are identified: the application of Sc and the heavy lanthanides to the development of novel magnesium alloys and the use of REEs as additives in the development of additive manufacturing of titanium parts., (© 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Determining the equilibrium wetting states and exploring the conditions and mechanisms of the wetting state transition from the Cassie-Baxter (CB) state to the Wenzel (W) state (CB-W transition) have been a central topic in the study of superhydrophobic behavior on rough or textured surfaces. Although considerable progress has been made, some issues regarding this topic are still not completely understood. In this study, a systematic thermodynamic analysis has been performed to address several key issues related to this topic. Generalized theoretical expressions for determining the equilibrium wetting states (the threshold Young contact angle of the CB region) and evaluating the stability of the CB state (the energy barrier separating the CB and W states and the critical pressure for the CB-W transition) have been derived. Applying these expressions to four types of surfaces built with protrusions in paraboloid, truncated cone, inverted truncated cone and flat-top pillar shapes, the wetting equilibrium and resultant wetting states have been studied. The physical meanings of the threshold Young contact angle, the roles and mechanisms of the energy barrier and critical pressure in stabilizing the CB state have been discussed. Finally, a general guidance for achieving robust superhydrophobicity on the studied surfaces has been given., Competing Interests: Declaration of Competing Interest All authors of this work have seen and approved the final version of the manuscript being submitted. The article is the authors' original work, has not received prior publication and is not under consideration for publication elsewhere. The authors have declared that no conflict of interest exists., (Copyright © 2020 Elsevier B.V. All rights reserved.)

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-CuZn 5 phase, and an intermetallic phase of TiZn 16 . 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., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020. Published by Elsevier Ltd.)

Some important factors in the design of biomaterials are surface characteristics such as surface chemistry and topography, which significantly influence the relationship between the biomaterial and host cells. Therefore, nanotubular oxide layers have received substantial attention for biomedical applications due to their potential benefits in the improvement of the biocompatibility of the substrate. In this study, a nanotubular layer of titania-niobium pentoxide-zirconia (TiO 2 -Nb 2 O 5 -ZrO 2 ) was developed via anodization on a β-type Ti35Zr28Nb alloy surface with enhanced biocompatibility. Scanning electron microscopy (SEM) and surface profilometry analysis of the anodized nanotubes indicated that the inner diameter ( D i ) and wall thicknesses ( W t ) increased with an increase in the water content of electrolyte and the applied voltage during anodization, while the nanotube length ( L n ) increased with increasing the anodization time. TiO 2 -Nb 2 O 5 -ZrO 2 nanotubes with different D i , W t , and L n showed different surface roughnesses ( R a ) and surface energies (γ), which affected the biocompatibility of the base alloy. MTS assay results showed that the TiO 2 -Nb 2 O 5 -ZrO 2 nanotubes with the largest inner diameter ( D i ) of 75.9 nm exhibited the highest cell viability of 108.55% due to the high γ of the surface, which led to high adsorption of proteins on the top surface of the nanotubes. The second highest cell viability was observed on the nanotubular surface with D i of 33.3 nm, which is believed to result from its high γ as well as the optimum spacing between nanotubes. R a did not appear to be clearly linked to cellular response; however, there may exist a threshold value of surface energy of ∼70 mJ/m 2 , below which the cell response is less sensitive and above which the cell viability increases with increasing γ. This indicates that the TiO 2 -Nb 2 O 5 -ZrO 2 nanotubes provided a suitable environment for enhanced attachment and growth of osteoblast-like cells as compared to the bare Ti35Zr28Nb alloy surface.

As a biodegradable metal (BM), alloys of magnesium (Mg) offer great potential as an alternative to the permanent metallic implants currently being used for fracture repairs and tissue-healing processes. These alloys exhibit superior biocompatibility and appropriate mechanical strength and dissolution behavior in the physiological environment, essential prerequisites for a BM. However, rapid and generally non-uniform corrosion has been the major drawback of Mg alloys. Abrupt deterioration in mechanical strength is experienced due to the inhomogeneous corrosion, which is also considered detrimental to the surface passivation process. This review has analyzed a variety of strategies that can be adopted to address the core challenges with Mg alloy biomaterials. In addition, the review provides fundamental understanding of the mechanisms associated with these challenging problems, including discussion of crystalline and bulk metallic glasses (BMGs) and composites. Comparison among the properties and mechanisms observed in other metal alloy systems, including zinc (Zn) and iron (Fe) alloys and prominent BMGs, are also presented for analysis in order to provide new approaches to resolving the critical issues of Mg alloys. STATEMENT OF SIGNIFICANCE: The effects of alloying elements, microstructure, heat treatment and deformation on the mechanical and corrosion properties of biodegradable metals such as Mg-based alloys and bulk metal glasses (BMGs) are identified. Theoretical models and experimental findings are comprehensively analyzed to corroborate the actual corrosion and deformation mechanisms observed in biodegradable metals (BMs). This work also provides an in-depth comparison of mechanical and corrosion properties among the prominent biodegradable metal alloy systems, illustrating a clear outlook on their potentials. The proposed strategies to address the current challenges in BMs are substantiated with fundamental theories and experimental evidence., (Copyright © 2019 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

Zinc (Zn) alloys have attracted much attention for biomedical applications due to their biodegradability, biocompatibility, and biological functionalities. Zn alloy foams have high potential to be used as regenerative medical implants by virtue of their porous structure, which allows new bone tissue ingrowth, their low elastic modulus approximating that of natural bone, and their biodegradation, which eliminates the need for follow-up surgery to remove the implants after bone tissue healing. In this context, a biodegradable Zn-Cu foam was fabricated by electrochemical deposition on a foamed Cu template and given a subsequent diffusion heat treatment. The microstructure, mechanical properties, degradation behavior, toxicity, hemolysis percentages, and antibacterial effects of the Zn-Cu foams were assessed for biomedical applications. The Zn-Cu foams exhibited a yield strength of ~12.1 MPa, a plateau strength of 16.8 MPa, and a strain over 50% under compression tests. The corrosion rate of the Zn-Cu foams measured by electrochemical polarization testing was 0.18 mm/y. The Zn-Cu foams showed good blood compatibility with a hemolysis percentage of less than 5%. Cytotoxicity assessment indicated that a 100% concentration of the Zn-Cu foam extract showed clear cytotoxicity against MC3T3-E1 osteoblast cells, but a 12.5% concentration of the extract showed > 90% cell viability. Moreover, the Zn-Cu foams showed good antibacterial effects. STATEMENT OF SIGNIFICANCE: This work reportsa biodegradable Zn-Cu foam with high mechanical strength and ductility, suitable degradation rate, good antibacterial capacity, and good hemolysis property and biocompatibility. The Zn-Cu foam exhibited a yield strength of ~12.1 MPa, a plateau strength of 16.8 MPa, and a strain over 50% under compression tests. The corrosion rate of the Zn-Cu foam measured by electrochemical polarization testing was 0.18 mm/y in Hanks' Solutions. The Zn-Cu foam showed good blood compatibility with a hemolysis percentage of less than 5%. Cytotoxicity assessment indicated that a 12.5% concentration of the foam extract showed > 90% cell viability. Moreover, the Zn-Cu foam showed good antibacterial effects against S. aureus., (Copyright © 2019. Published by Elsevier Ltd.)

Magnesium (Mg) and its alloys are considered promising biodegradable implant materials because of their strength and natural degradation in the human body. However, the high corrosion rate of pure Mg in the physiological environment leads to rapid degradation before adequate bone healing. This mismatch between bone healing and the degradation of Mg implants supports the development of new Mg alloys with the addition of other suitable alloying elements in order to achieve simultaneously high corrosion resistance and desirable mechanical properties. This study systematically investigates the microstructure, mechanical properties, corrosion behavior, and biocompatibility of Mg-based alloys with the addition of different concentrations of scandium (Sc), i.e., Mg-0.6Zr-0.5Sr-xSc (x = 0.5, 1, 2, 3 wt.%). Results indicated that high concentration of Sc in strontium (Sr)-containing Mg alloys can alter their microstructures by suppressing the intermetallic phases along the grain boundaries and improve the corrosion resistance by forming chemically stable Sc oxide layers on the surfaces of the Mg alloys. Cytotoxicity assessment revealed that the Sc containing Mg alloys did not significantly alter the viability of human osteoblast-like SaOS2 cells. This study highlights the advantages of using Sc as an alloying element to simultaneously tune Mg alloys with higher strength and slower degradation. STATEMENT OF SIGNIFICANCE: Rare earth elements such as scandium (Sc) with both a high solid-solubility and strong affinity towards oxygen can improve the mechanical and corrosion properties of magnesium (Mg) alloys. However, the feasibility of Sc-containing Mg alloys as biodegradable implant materials is scarcely reported. This study investigates the effects of different Sc concentrations on the mechanical, corrosion, and biocompatibility properties of Mg-Zr-Sr-Sc alloys. Our findings indicated that the addition of Sc significantly improves the mechanical and corrosion properties of Mg-Zr-Sr alloys. Moreover, in vitro cytotoxicity assessment of the Mg-Zr-Sr-Sc alloys did not show any adverse effects on the viability of osteoblast-like cells., (Copyright © 2019 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

In this study, the microstructural evolution and mechanical properties of a newly developed Ti-40.7Zr-24.8Nb (TZN) alloy after different thermomechanical processes were examined. As-cast TZN alloy plates were solution-treated at 890 °C for 1 h, after which the thickness of the alloy plates was reduced by cold rolling at reduction ratios of 20%, 56%, 76%, and 86%. Stress-induced α" formation, {332} <113> β mechanical twinning, and kink band formation were observed in the cold-rolled TZN alloy samples. In the TZN sample after cold rolling at the 86% reduction ratio plus a recrystallization annealing at 890 °C for 1 h, the deformation products of a stress-induced α" phase, {332}<113> β mechanical twinning, and kink bands disappeared, resulting in a fine, equiaxed single β phase. The alloy samples exhibited elongation at rupture ranging from 7% to 20%, Young's modulus ranging from 63 to 72 GPa and tensile strength ranging from 753 to 1158 MPa. The TZN alloy sample after cold rolling and recrystallization annealing showed a yield strength of 803 MPa, a tensile strength of 848 MPa, an elongation at rupture of 20%, and an elastic admissible strain of 1.22%, along with the most ductile fractures during tensile testing., Competing Interests: The authors declare that there are no conflicts of interest., (© Trade Vocational College, Wenzhou, Zhejiang, 325003, China.)

The present study investigates the nanoindentation behavior, wear resistance and in vitro biocompatibility of SLM manufactured CP-Ti and EBM manufactured Ti64 gyroid scaffolds and the results were compared to those of casting CP-Ti. Both the SLM- and EBM manufactured scaffolds exhibited anisotropic properties with higher reduced modulus (up to 10%) and nanohardness (up to 30%) in the transverse direction than those in building direction. The wear resistance of scaffolds in transverse direction was higher than those of in building direction by up to ∼25% and ∼82% for SLM manufactured CP-Ti and EBM manufactured Ti64 scaffolds, respectively. The SLM manufactured CP-Ti scaffolds displayed significant enhancement in wear resistance over cast dense CP-Ti with 75% lower mean worn height during a nanowear test. The coefficient of friction was varied between 0.11 and 0.24 and exhibited a steady mean value of 0.15-0.18 for CP-Ti and Ti64 scaffolds, respectively. During in vitro cell culture study, CP-Ti scaffolds showed higher cell viability and cell adhesion density in comparison to Ti64 scaffolds for all unit cell sizes. Moreover, cell adhesion density of scaffolds with smaller unit cell sizes (G2) are lower than those of larger unit cells (G3). SEM observations confirmed that both the inner space and surfaces of gyroid scaffolds provided a suitable environment for cell migration, attachment and proliferation after cell culture for 7 d. STATEMENT OF SIGNIFICANCE: It is essential to evaluate the properties of EBM/SLM manufactured scaffolds and to determine whether they can meet the tough performance requirements of the biomedical industry. In this study, nanoindentation and nanowear properties of SLM manufactured CP-Ti and EBM manufactured Ti64 gyroid scaffolds with different unit cell sizes and sample orientations were evaluated and compared to cast dense CP-Ti samples. Moreover, the in vitro biocompatibility of the scaffolds was assessed and compared to each other. To our best of knowledge, this type of study on EBM/SLM manufactured CP-Ti and Ti64 scaffolds have not been reported, to date., (Copyright © 2019 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

Magnesium (Mg) and some of its alloys have attracted extensive interests for biomedical applications as they exhibit biodegradability and low elastic modulus that is closer to natural bones than the currently used metallic implant materials such as titanium (Ti) and its alloys, stainless steels, and cobalt-chromium (Co-Cr) alloys. However, the rapid degradation of Mg alloys and loss of their mechanical integrity before sufficient bone healing impede their clinical application. Our literature review shows that magnesium matrix nanocomposites (MMNCs) reinforced with nanoparticles possess enhanced strength, high corrosion resistance, and good biocompatibility. This article provides a detailed analysis of the effects of nanoparticle reinforcements on the mechanical properties, corrosion behavior, and biocompatibility of MMNCs as promising biodegradable implant materials. The governing equations to quantitatively predict the mechanical properties and underlying synergistic strengthening mechanisms in MMNCs are elucidated. The potential, recent advances, challenges and future research directions in relation to nanoparticles reinforced MMNCs are highlighted. STATEMENT OF SIGNIFICANCE: Critically reviewing magnesium metal matrix nanocomposites (MMNCs) for the biomedical application. Clear definitions of strengthening mechanisms using reinforcement particle in the magnesium matrix, as there were controversial in governing equations of strengthening parameters. Providing better understanding of the effect of particle size, volume fraction, interfacial bonding, and uniform dispersion of reinforcement particles on MMNCs., (Copyright © 2019 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

The nanostructured surface modification of metallic implants is increasingly gaining attention for biomedical applications. Among such nanostructured surfaces, oxide nanotube (NT) structures have received significant consideration in the biomedical and clinical fields, particularly because of their unique biological characteristics. This experimental study is based on the optimization and characterization of TiO 2 -Nb 2 O 5 -ZrO 2 nanotubes (NTs) on newly developed β phase TiZr 35 Nb 28 alloy. The effects of the anodization process parameters on the inner diameter ( D i ) of the NTs were investigated. The experiment was conducted using the Taguchi experimental design with an L 9 (3 3 ) orthogonal array, with three control factors targeted for optimization: (i) applied voltage, (ii) water content of the electrolyte solution, and (iii) anodization time. The chemical composition, morphology, and hydrophilic properties of TiO 2 -Nb 2 O 5 -ZrO 2 NTs after optimization were characterized by energy-dispersive X-ray spectroscopy (EDX), scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS), and water contact angle measurement. The results showed that a large D i of NTs was achieved using an applied voltage of 40 V, water content of 5%, and anodization time of 120 min, with the applied voltage identified as the most effective parameter for the growth of TiO 2 -Nb 2 O 5 -ZrO 2 NTs based on signal-to-noise (S/N) ratio analysis. The Pareto ANOVA and confirmation test results showed that the Taguchi method was successful in optimizing the larger D i for NTs; moreover, the optimized nanotubular surface exhibited the highest surface roughness and an increased hydrophilic nature. The above findings may contribute to the development of high-performance nanostructured coatings for biomedical applications.

Coatings based on ion-substituted calcium phosphate (Ca-P) have attracted great attention in the scientific community over the past decade for the development of biomedical applications. Among such Ca-P based structures, hydroxyapatite (HA) has shown significant influence on cell behaviors including cell proliferation, adhesion, and differentiation. These cell behaviors determine the osseointegration between the implant and host bone and the biocompatibility of implants. This review presents a critical analysis on the physical vapor deposition magnetron sputtering (PVDMS) technique that has been used for ion-substituted Ca-P based coatings on implants materials. The effect of PVDMS processing parameters such as discharge power, bias voltage, deposition time, substrate temperature, and post-heat treatment on the surface properties of ion-substituted Ca-P coatings is elucidated. Moreover, the advantages, short comings and future research directions of Ca-P coatings by PVDMS have been comprehensively analyzed. It is revealed that the topography and surface chemistry of amorphous HA coatings influence the cell behavior, and ion-substituted HA coatings significantly increase cell attachment but may result in a cytotoxic effect that reduces the growth of the cells attached to the coating surface areas. Meanwhile, low-crystalline HA coatings exhibit lower rates of osteogenic cell proliferation as compared to highly crystalline HA coatings developed on Ti based surfaces. PVDMS allows a close reproduction of bioapatite characteristics with high adhesion strength and substitution of therapeutic ions. It can also be used for processing nanostructured Ca-P coatings on polymeric biomaterials and biodegradable metals and alloys with enhanced corrosion resistance and biocompatibility. STATEMENT OF SIGNIFICANCE: Recent studies have utilized the physical vapor deposition magnetron sputtering (PVDMS) for the deposition of Ca-P and ion-substituted Ca-P thin film coatings on orthopedic and dental implants. This review explains the effect of PVDMS processing parameters, such as discharge power, bias voltage, deposition time, substrate temperature, and post-heat treatment, on the surface morphology and crystal structure of ion-substituted Ca-P and ion-substituted Ca-P thin coatings. It is revealed that coating thickness, surface morphology and crystal structure of ion-substituted Ca-P coatings via PVDMS directly affect the biocompatibility and cell responses of such structures. The cell responses determine the osseointegration between the implant and host bone and eventually the success of the implants., (Copyright © 2019 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

Titanium (Ti) based tissue engineering scaffolds can be used to repair damaged bone. However, successful orthopedic applications of these scaffolds rely on their ability to mimic the mechanical properties of trabecular bone. Selective laser melting (SLM) was used to manufacture scaffolds of a new β-Ti35Zr28Nb alloy for biomedical applications. Porosity values of the scaffolds were 83% for the FCCZ structure (face centered cubic unit cell with longitudinal struts) and 50% for the FBCCZ structure (face and body centered cubic unit cell with longitudinal struts). The scaffolds had an elastic modulus of ∼1 GPa and a plateau strength of 8-58 MPa, which fall within the values of trabecular bone (0.2-5 GPa for elastic modulus and 4-70 MPa for compressive strength). The SLM-manufactured β-Ti35Zr28Nb alloy showed good corrosion properties. MTS assay revealed that both the FCCZ and FBCCZ scaffolds had a cell viability similar to the control. SEM observation indicated that the osteoblast-like cells adhered, spread and grew healthily on the surface of both scaffolds after culture for 7, 14 and 28 d, demonstrating good biocompatibility. Overall, the SLM-manufactured Ti35Zr28Nb scaffolds possess promising potential as hard-tissue implant materials due to their appropriate mechanical properties, good corrosion behavior and biocompatibility. STATEMENT OF SIGNIFICANCE: Novel β Ti35Zr28Nb alloy scaffolds with FCCZ and FBCCZ structures were successfully fabricated by selective laser melting (SLM) for biomedical applications. The scaffolds showed values of elastic modulus of ∼1 GPa and plateau strength of 8-58 MPa, which fall within the ranges of the mechanical properties of trabecular bone. The SLM-manufactured β Ti35Zr28Nb alloy showed good corrosion properties. Both SLM-manufactured FCCZ and FBCCZ scaffolds exhibited good biocompatibility, with osteoblast-like cells attaching, growing, and spreading in a healthy way on their surfaces after culturing for different periods up to 28 d., (Copyright © 2019 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

Current challenges in existing metallic biomaterials encourage undertaking research in the development of novel materials for biomedical applications. This paper critically reviews the potential of carbon nanotubes (CNT) and graphene as nanoreinforcements in metallic biomaterials for bone tissue engineering. Unique and remarkable mechanical, electrical, and biological properties of these carbon nanomaterials allow their use as secondary-phase reinforcements in monolithic biomaterials. The nanoscale dimensions and extraordinarily large surface areas of CNT and graphene make them suitable materials for purposeful reaction with living organisms. However, the cytocompatibility of CNT and graphene is still a controversial issue that impedes advances in utilizing these promising materials in clinical orthopedic applications. The interaction of CNT and graphene with biological systems including proteins, nucleic acids, and human cells is critically reviewed to assess their cytocompatibity in vitro and in vivo. It is revealed that composites reinforced with CNT and graphene show enhanced adhesion of osteoblast cells, which subsequently promotes bone tissue formation in vivo. This potential is expected to pave the way for developing ground-breaking technologies in regenerative medicine and bone tissue engineering. In addition, current progress and future research directions are highlighted for the development of CNT and graphene reinforced implants for bone tissue engineering., (© 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Zinc (Zn)-based alloys are considered a new class of biodegradable implant materials due to their superior chemical stability and processability compared to biodegradable magnesium (Mg) alloys. In this study, we report a new biodegradable Zn-5Ge alloy with highly desirable mechanical, corrosion, and biological properties. Microstructural characterization revealed the effective grain-refining effect of germanium (Ge) on the Zn alloy. Tensile test results indicated that the hot-rolled Zn-5Ge alloy showed an ultimate tensile strength of 237.0 MPa, a yield strength of 175.1 MPa, and an elongation of 21.6%; while as-cast pure Zn showed an ultimate tensile strength of 33.6 MPa, a yield strength of 29.3 MPa, and an elongation of 1.2%. The corrosion rates measured by potentiodynamic polarization tests in Hank's solution in ascending order are: as-cast Zn-5Ge (0.1272 mm/y) < as-cast pure Zn (0.1567 mm/y) < hot-rolled Zn-5Ge (0.2255 mm/y) < hot-rolled pure Zn (0.3057 mm/y). Immersion tests revealed that the degradation rate of as-cast Zn-5Ge is 0.042 mm/y, less than half of that of hot-rolled pure Zn and ∼62% of that of as-cast pure Zn. Moreover, the Zn-5Ge alloy showed excellent in vitro hemocompatibility and the addition of 5% Ge effectively enhanced the hemocompatibility of pure Zn. CCK-8 assay using murine preosteoblast MC3T3-E1 cells indicated that the diluted extracts at a concentration <12.5% of both the as-cast Zn-5Ge alloy and pure Zn showed grade 0 cytotoxicity; the diluted extracts at the concentrations of 50% and 25% of Zn-5Ge alloy showed a significantly higher cell viability than those of pure Zn. STATEMENT OF SIGNIFICANCE: Zinc (Zn)-based alloys are currently considered a new class of biodegradable implant materials due to their excellent processability. Here, we report a novel Zn-5Ge alloy with highly desirable mechanical, corrosion and biological properties. The tensile test results indicated that the hot-rolled Zn-5Ge alloy showed an ultimate tensile strength of 237.0 MPa, a yield strength of 175.1 MPa and an elongation of 21.6%; while as-cast pure Zn showed an ultimate tensile strength of 33.6 MPa, a yield strength of 29.3 MPa and an elongation of 1.2%. The corrosion rate measured by potentiodynamic polarization tests in Hank's solution in the ascending order is: as-cast Zn-5Ge (0.1272 mm/y) < as-cast pure Zn (0.1567 mm/y) < hot-rolled Zn-5Ge (0.2255 mm/y) < hot-rolled pure Zn (0.3057 mm/y). Immersion tests revealed that the degradation rate of the as-cast Zn-5Ge is 0.042 mm/y, less than half of that of the hot-rolled pure Zn, ∼62% of that of as-cast pure Zn. Moreover, the Zn-5Ge alloy showed excellent in vitro biocompatibility., (Copyright © 2018 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

The application of various materials in biomedical procedures has recently experienced rapid growth. One area that is currently receiving significant attention from the scientific community is the treatment of a number of different types of bone-related diseases and disorders by using biodegradable polymer-ceramic composites. Biomaterials, the most common materials used to repair or replace damaged parts of the human body, can be categorized into three major groups: metals, ceramics, and polymers. Composites can be manufactured by combining two or more materials to achieve enhanced biocompatibility and biomechanical properties for specific applications. Biomaterials must display suitable properties for their applications, about strength, durability, and biological influence. Metals and their alloys such as titanium, stainless steel, and cobalt-based alloys have been widely investigated for implant-device applications because of their excellent mechanical properties. However, these materials may also manifest biological issues such as toxicity, poor tissue adhesion and stress shielding effect due to their high elastic modulus. To mitigate these issues, hydroxyapatite (HA) coatings have been used on metals because their chemical composition is similar to that of bone and teeth. Recently, a wide range of synthetic polymers such as poly (l-lactic acid) and poly (l-lactide- co -glycolide) have been studied for different biomedical applications, owing to their promising biocompatibility and biodegradability. This article gives an overview of synthetic polymer-ceramic composites with a particular emphasis on calcium phosphate group and their potential applications in tissue engineering. It is hoped that synthetic polymer-ceramic composites such as PLLA/HA and PCL/HA will provide advantages such as eliminating the stress shielding effect and the consequent need for revision surgery.

This study investigates the microstructure, mechanical properties, corrosion behavior, and biocompatibility of magnesium (Mg)-based Mg1Zr2SrxDy (x = 0, 1, 1.63, 2.08 wt %) alloys for biodegradable implant applications. The corrosion behavior of the Mg-based alloys has been evaluated in simulated body fluid using an electrochemical technique and hydrogen evolution. The biocompatibility of the Mg-based alloys has been assessed using SaSO2 cells. Results indicate that the addition of Dy to Mg-Zr-Sr alloy showed a positive impact on the corrosion behavior and significantly decreased the degradation rates of the alloys. The degradation rate of Mg1Zr2Sr1.0Dy decreased from 17.61 to 12.50 mm year -1 of Mg1Zr2Sr2.08Dy based on the hydrogen evolution. The ultimate compressive strength decreased from 270.90 MPa for Mg1Zr2Sr1Dy to 236.71 MPa for Mg1Zr2Sr2.08Dy. An increase in the addition of Dy to the Mg-based alloys resulted in an increase in the volume fraction of the Mg 2 Dy phase, which mitigated the galvanic effect between the Mg 17 Sr 2 phase and the Mg matrix, and led to an increase in the corrosion resistance of the base alloy. The biocompatibility of the Mg-based alloys was enhanced with decreasing corrosion rates. Mg1Zr2Sr2.08Dy exhibited the lowest corrosion rate and the highest biocompatibility compared with the other Mg-based alloys. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 2425-2434, 2018., (© 2017 Wiley Periodicals, Inc.)

Alloys comprised of the highly biocompatible elements titanium, niobium and zirconium have been a major focus in recent years in the field of metallic biomaterials. To contribute to the corpus of data in this field, the current paper presents results from a thorough microstructural and mechanical investigation of Ti-32Nb-6Zr subjected to a variety of ageing treatments. The presented alloy was stabilized to the higher temperature, body-centred cubic phase, showing only minimal precipitation on prolonged ageing, despite the presence of nanoscaled spinodal segregation arising from the Nb-Zr interaction. It further showed excellent mechanical properties, with tensile yield stresses as high as 820 MPa and Young's moduli as low as 53 GPa. This leads to the ratio of strength to modulus, also known as the admissible strain, reaching a maximum of 1.3% after 6 hours ageing. These results are further supported by similar measurements from nanoindentation analysis.

The effects of thermomechanical treatment on the microstructure and mechanical properties of a newly developed β titanium alloy, i.e., Ti-28Nb-35.4Zr (wt%, hereafter denoted Ti-Nb-Zr) were investigated. The as-cast Ti-Nb-Zr alloy was subjected to solution treatment at 890°C for 1h, after which its thickness was reduced by 20%, 56%, 76%, and 86% via cold rolling. Results indicated that annealing at 890°C for 1h after cold rolling at a thickness reduction ratio of 86% resulted in a phase transformation from the stress-induced α" and ω into β, leading to a recrystallization of a uniform single β phase. The recrystallized Ti-Nb-Zr alloy exhibited a tensile strength of 633MPa, Young's modulus of 63GPa, and elongation at rupture of 13%, respectively. The cold rolled specimens showed a higher Young's modulus than that of the recrystallized specimen due to the stress-induced ω phase. Transmission electron microscopy (TEM) analysis revealed that ω, α" and β phases co-existed in the microstructure of the cold-rolled specimens. Electron backscatter diffraction analysis revealed that the deformation mechanisms during thermomechanical processing included kink bands, {332}<113> twins and shear bands; and the predominant deformation mechanism depended on the extent of CR deformation., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

The conveniently obtained water-soluble small-molecule L1-5 were selective for RNA with remarkable "off-on" two-photon fluorescence responses in vitro and in vivo, showing that L1-5 can surprisingly stain mitochondria or nucleoli individually with orange fluorescence under different focal lengths. Compounds L6-8 were prepared, for comparison, to further explore the mechanism of the binding of L1-5 with RNA, which revealed that the synergistic effect of the amino group and the pyridinium cation played a significant role in distinct cell imaging.

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 (Mo eq ). X-ray diffraction analysis has revealed that all the TTZN alloys are comprised of a single β phase, however, transmission electron microscopy observations revealed that ω and β 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., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

While titanium alloys represent the current state-of-the-art for orthopedic biomaterials, concerns still remain over their modulus. Circumventing this via increased porosity requires high elastic admissible strains, yet also limits traditional thermomechanical strengthening techniques. To this end, a novel β-type Ti-Zr-Ta alloy system, comprised of Ti-45Zr-10Ta, Ti-40Zr-14Ta, Ti-35Zr-18Ta and Ti-30Zr-22Ta, was designed and characterized mechanically and microstructurally. As-cast, this system displayed extremely high yield strengths and elastic admissible strains, up to 1.4GPa and potentially 1.48%, respectively. This strength was attributed to a nanoscaled, cuboidal structure of semi-coherent, dual body-centered cubic (BCC) phases, arising from the thermodynamics of interaction between Ta and Zr; this morphology occurring with dual BCC-phases is heretofore unreported in Ti-based alloys. Further, cell proliferation investigated by MTS assay suggests this was achieved without sacrificing biocompatibility, with no significant difference to either empty-well or commercially-pure Ti controls noted., Statement of Significance: The current research details microstructural, mechanical, and biological investigations into four novel biomedical alloys in a hitherto uninvestigated region of the Ti-Zr-Ta alloy system; Ti-45Zr-10Ta, Ti-40Zr-14Ta, Ti-35Zr-18Ta and Ti-30Zr-22Ta. We find that the investigated alloys display 0.2% yield strengths of up to 1.40GPa and elastic admissible strains of up to 1.48%, along with biological properties comparable to that seen in the conventional metallic biomaterial ASTM Grade-2 CP-Ti, achieved in the complete absence of traditional thermomechanical processing techniques. This is attributed to the presence of a dual-BCC cuboidal nanostructure, achieved via spinodal decomposition; while similar structures have been reported in e.g. Ni-based superalloys, we believe this is the first such structure investigated in a Ti-based material. As such, this work is felt to be of great interest in aiding the design and manufacture of highly-biocompatible, porous, metallic biomaterials for orthopedic application., (Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

In this paper, we present further work on the influence of minor additions of Ru to the Ti-20Nb alloy system, with a primary focus on mechanical properties of the as-cast material, along with microstructural response to elevated temperatures. Findings include high as-cast strengths and admissible strain values, up to 920MPa and 1.5% respectively, along with moduli down to approximately 65GPa in the as-cast state. Together with a significant increase in cell proliferation under MTS assay relative to controls, this indicates the chosen alloy system has significant promise for application in porous orthopaedic biomaterials, in particular those alloys with 0.5-1.0% Ru are deemed most suitable. Given their promise, preliminary investigation of the alloy system's response to thermal treatment was also undertaken., Statement of Significance: The presented research, an investigation into the mechanical properties and response to thermal treatments of Ru-containing Ti-20Nb-base alloys, holds significance in the field of metallic biomaterials due to the heretofore limited investigation into the impact of Ru on the properties of biomedical, β-phase, Ti-based alloys. Given Ru's known beneficial impact on corrosion resistance, experimental confirmation of the impact of addition on mechanical properties was needed; that suitable mechanical properties, including yield strengths up to ∼930MPa along with elastic admissible strains approaching 1.5%, were achieved is both promising in and of itself, and of significant note for further research into the field. Preliminary thermal and cell-proliferation studies are additionally provided to inform further studies., (Copyright © 2016 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

Elemental metals have been widely used to alloy metallic orthopedic implants. However, there is still insufficient research data elucidating the cell responses of osteoblastic cells to alloying elemental metals, which impedes the development of new metallic implant materials. In this study, the cellular responses of osteoblast-like cells (SaOS2) to 17 pure alloying elemental metals, that is, titanium (Ti), zirconium (Zr), hafnium (Hf), vanadium (V), niobium (Nb), tantalum (Ta), chromium (Cr), molybdenum (Mo), manganese (Mn), iron (Fe), ruthenium (Ru), cobalt (Co), nickel (Ni), copper (Cu), zinc (Zn), silicon (Si), and tin (Sn) were comparatively investigated in vitro. Cellular responses including intracellular total protein synthesis and collagen content, cell adhesion, cell proliferation, and alkaline phosphatase (ALP) activity on these elemental metals were systematically assessed and compared. It was found that these elemental metals could be categorized into three groups based on the cellular functions on them. Group 1, including Ti, Zr, Hf, Nb, Ta, Cr, Ru, and Si, showed excellent cell proliferation and varied ALP activity for SaOS2 cells. Cells exposed to Group 2, including Mo and Sn, although initially attached and grew, did not proliferate over time. In contrast, Group 3, including V, Mn, Fe, Co, Ni, Cu, and Zn, showed severe cytotoxicity toward SaOS2 cells. It is vital to consider the cell responses to the elemental metals when designing a new metallic implant material and the findings of this study provide insights into the biological performance of the elemental metals. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 148-158, 2017., (© 2016 Wiley Periodicals, Inc.)