A biodegradable Zn-5Gd alloy with biomechanical compatibility, cytocompatibility, antibacterial ability, and in vitro and in vivo osteogenesis for orthopedic applications.

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.

Biodegradable Zn-5Dy Alloy with Enhanced Osteo/Angio-Genic Activity and Osteointegration Effect via Regulation of SIRT4-Dependent Mitochondrial Function.

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.

Enhanced Mechanical Properties, Corrosion Resistance, Cytocompatibility, Osteogenesis, and Antibacterial Performance of Biodegradable Mg-2Zn-0.5Ca-0.5Sr/Zr Alloys for Bone-Implant Application.

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.

Mechanical properties, corrosion behavior, and cytotoxicity of biodegradable Zn/Mg multilayered composites prepared by accumulative roll bonding process.

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.

Mechanical properties, corrosion and degradation behaviors, and in vitro cytocompatibility of a biodegradable Zn-5La alloy for bone-implant applications.

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.

An Optimized Method for Microcomputed Tomography Analysis of Trabecular Parameters of Metal Scaffolds for Bone Ingrowth.

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.

Microstructures, mechanical and corrosion properties of graphene nanoplatelet-reinforced zinc matrix composites for implant applications.

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.

Biodegradable Zn-Dy binary alloys with high strength, ductility, cytocompatibility, and antibacterial ability for bone-implant applications.

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.

Mechanical, corrosion, nanotribological, and biocompatibility properties of equal channel angular pressed Ti-28Nb-35.4Zr alloys for biomedical applications.

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 ß Ti-28Nb-35.4Zr (hereafter denoted TNZ) alloy. Results indicated that ECAP of the ß TNZ alloy refined its microstructure by forming ultrafine grains without causing stress-induced phase transformation, leading to formation of a single ß 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 ß Ti-28Nb-35.4Zr (TNZ) alloy processed via ECAP. Our findings indicated that ECAP of the ß 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.

A biodegradable Fe/Zn-3Cu composite with requisite properties for orthopedic applications.

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 CuZn5 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.

A biodegradable in situ Zn-Mg2Ge composite for bone-implant applications.

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-xMg2Ge (x = 1, 3, and 5 wt.%) composites for bone-implant applications. The mechanical properties of Zn-xMg2Ge composites were effectively improved by alloying and hot-rolling due to particle reinforcement of the Mg2Ge intermetallic phase and dynamic recrystallization. The hot-rolled (HR) Zn-3Mg2Ge 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 Mg2Ge content, the corrosion and degradation rates of the HR Zn-xMg2Ge composites gradually increased, while their wear rate decreased and then increased in Hanks' solution. The diluted extract (12.5% concentration) of the HR Zn-3Mg2Ge composite showed the highest cell viability compared to the other HR composites and their as-cast pure Zn counterparts. Overall, the HR Zn-3Mg2Ge 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-xMg2Ge (x = 1, 3, and 5 wt.%) composites for bone-implant applications. Our findings demonstrated that the mechanical properties of Zn-xMg2Ge composites were effectively improved by alloying and hot-rolling due to Mg2Ge particle reinforcement and dynamic recrystallization. The hot-rolled Zn-3Mg2Ge 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%.

Impact of gadolinium on mechanical properties, corrosion resistance, and biocompatibility of Zn-1Mg-xGd alloys for biodegradable bone-implant applications.

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%.

In vitro and in vivo assessment of the effect of biodegradable magnesium alloys on osteogenesis.

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.

Impact of scandium on mechanical properties, corrosion behavior, friction and wear performance, and cytotoxicity of a ß-type Ti-24Nb-38Zr-2Mo alloy for orthopedic applications.

ß-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 ß-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/cm2, 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 ß-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.

A review of the physiological impact of rare earth elements and their uses in biomedical Mg alloys.

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.

Surface Characterization and Biocompatibility of Hydroxyapatite Coating on Anodized TiO2 Nanotubes via PVD Magnetron Sputtering.

Hydroxyapatite (HA) coating has received significant attention in the scientific community for the development of implants, and HA coating on titanium oxide (TiO2) nanotubes has shown potential benefits in the improvement of cell proliferation, adhesion, and differentiation. In this study, a HA coating on a TiO2 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 TiO2 nanotubes influenced the surface roughness (Ra) and hydrophilicity. The XRD and FTIR peaks indicated the presence of crystalline phases of TiO2 (anatase) and HA-coated TiO2 nanotubes after annealing at 500 °C for 120 min. The HA-coated TiO2 nanotubes showed significantly increased Ra and decreased water contact angle (θ) compared to the as-anodized TiO2 nanotubular and bare CP-Ti surfaces. MTS assay using osteoblast-like cells confirmed that the HA-coated TiO2 nanotubular surface provided an enhanced cell attachment and growth when compared to as-anodized TiO2 nanotubular and pure CP-Ti surfaces.

Biodegradable Zn-3Mg-0.7Mg2Si composite fabricated by high-pressure solidification for bone implant applications.

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-0.7Mg2Si composite fabricated by high-pressure solidification. Microstructural characterization revealed that the high-pressure solidified (HPS) composite exhibited uniformly distributed fine MgZn2 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/cm2, 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-0.7Mg2Si composite can be anticipated as a promising biodegradable material for orthopedic applications.

Recent research and progress of biodegradable zinc alloys and composites for biomedical applications: Biomechanical and biocorrosion perspectives.

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.

Development of biodegradable Zn-1Mg-0.1RE (RE = Er, Dy, and Ho) alloys for biomedical applications.

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 ErZn5, DyZn5, and Ho2Zn17 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.

Biodegradable ternary Zn-3Ge-0.5X (X=Cu, Mg, and Fe) alloys for orthopedic applications.

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.