The effect of selected alloying element additions on properties of Mg-based alloy as bioimplants: A literature review

This review investigates the current application limitations of Mg and Mg alloys. The key issues hindering the application of biodegradable Mg alloys as implants are their fast degradation rate and biological consideration. We have discussed the effect of some selected alloying element additions on the properties of the Mg-based alloy, especially the nutrient elements in human (Zn, Mn, Ca, Sr). Different grain sizes, phase constituents and distributions consequently influence the mechanical properties of the Mg alloys. Solution strengthening and precipitation strengthening are enhanced by the addition of alloying elements, generally improving the mechanical properties. Besides, the hot working process can also improve the mechanical properties. Combination of different processing steps is suggested to be adopted in the fabrication of Mg-based alloys. Corrosion properties of these Mg-based alloys have been measured in vitro and in vivo. The degradation mechanism is also discussed in terms of corrosion types, rates, by-products and response of the surrounding tissues. Moreover, the clinical response and requirements of degradable implants are presented, especially for the nutrient elements (Ca, Mn, Zn, Sr). This review provides information related to different Mg alloying elements and presents the promising candidates for an ideal implant.     

Enhanced biocorrosion resistance and biocompatibility of degradable Mg–Nd–Zn–Zr alloy by brushite coating

To further improve the corrosion resistance and biocompatibility of Mg–Nd–Zn–Zr alloy (JDBM), a biodegradable calcium phosphate coating (Ca–P coating) with high bonding strength was developed using a novel chemical deposition method. The main composition of the Ca–P coating was brushite (CaHPO₄·2H₂O). The bonding strength between the coating and the JDBM substrate was measured to be over 10 MPa, and the thickness of the coating layer was about 10–30 μm. The in vitro corrosion tests indicated that the Ca–P treatment improved the corrosion resistance of JDBM alloy in Hank's solution. Ca–P treatment significantly reduced the hemolysis rate of JDBM alloy from 48% to 0.68%, and induced no toxicity to MC3T3-E1 cells. The in vivo implantation experiment in New Zealand's rabbit tibia showed that the degradation rate was reduced obviously by the Ca–P treatment and less gas was produced from Ca–P treated JDBM bone plates and screws in early stage of the implantation, and at least 10 weeks degradation time can be prolonged by the present coating techniques. Both Ca–P treated and untreated JDBM Mg alloy induced bone growth. The primary results indicate that the present Ca–P treatment is a promising technique for the degradable Mg-based biomaterials for orthopedic applications.     

In vitro degradation of four magnesium–zinc–strontium alloys and their cytocompatibility with human embryonic stem cells

Magnesium alloys have attracted great interest for medical applications due to their unique biodegradable capability and desirable mechanical properties. When designed for medical applications, these alloys must have suitable degradation properties, i.e., their degradation rate should not exceed the rate at which the degradation products can be excreted from the body. Cellular responses and tissue integration around the Mg-based implants are critical for clinical success. Four magnesium–zinc–strontium (ZSr41) alloys were developed in this study. The degradation properties of the ZSr41 alloys and their cytocompatibility were studied using an in vitro human embryonic stem cell (hESC) model due to the greater sensitivity of hESCs to known toxicants which allows to potentially detect toxicological effects of new biomaterials at an early stage. Four distinct ZSr41 alloys with 4 wt% zinc and a series of strontium compositions (0.15, 0.5, 1, and 1.5 wt% Sr) were produced through metallurgical processing. Their degradation was characterized by measuring total mass loss of samples and pH change in the cell culture media. The concentration of Mg ions released from ZSr41 alloy into the cell culture media was analyzed using inductively coupled plasma atomic emission spectroscopy. Surface microstructure and composition before and after culturing with hESCs were characterized using field emission scanning electron microscopy and energy dispersive X-ray spectroscopy. Pure Mg was used as a control during cell culture studies. Results indicated that the Mg–Zn–Sr alloy with 0.15 wt% Sr provided slower degradation and improved cytocompatibility as compared with pure Mg control.     

Biocorrosion properties of as-extruded Mg-Nd-Zn-Zr alloy compared with commercial AZ31 and WE43 alloys

A new type of patented biodegradable biomedical magnesium alloy Mg-Nd-Zn-Zr (hereafter, denoted as JDBM) was prepared in this study. The biocorrosion properties of the as-extruded JDBM alloy were investigated in simulated body fluid (SBF) by hydrogen evolution, mass loss and electrochemical tests. The biocorrosion properties of as-extruded AZ31 and as-extruded WE43 alloys as well as the mechanical properties at room temperature were also studied in order to compare with the novel JDBM biodegradable biomedical magnesium alloy. The results show that the as-extruded JDBM alloy not only owns much better mechanical properties at room temperature but also exhibits much better biocorrosion properties in SBF.     

Comparison of biodegradable behaviors of AZ31 and Mg–Nd–Zn–Zr alloys in Hank's physiological solution

The main challenge for the application of magnesium and its alloy as degradable biomaterials lies in their high degradation rates in physiological environment. In the present work, the biodegradable behavior of a patent magnesium alloy Mg–Nd–Zn–Zr (JDBM) and a reference alloy AZ31 was systematically investigated in Hank's physiological solution. The corrosion rate of JDBM (0.28 mm/year) was much slower than that of AZ31 (1.02 mm/year) in Hank's solution for 240 h. After corrosion products were removed, smooth surface of the JDBM was observed by SEM observation compared to many deep pits on the surface of AZ31. Open-circuit potential and potentiodynamic polarization results manifested that pitting corrosion did not occurred on the surface of JDBM at the early period of immersion time due to the formation of a more protective and compact film layer suggested by electrochemical impedance spectroscopy study. The corrosion rate of magnesium alloys was found to slow down in dynamic corrosion in comparison with that in the static corrosion. This provided the basis for scientific evaluation of in vitro and in vivo corrosion behavior for degradable biomagnesium alloy. The present results suggest that the new patent magnesium alloy JDBM is a promising candidate as degradable biomaterials and is worthwhile for further investigation in vivo corrosive environment.     

Bio-corrosion characterization of Mg–Zn–X (X = Ca, Mn, Si) alloys for biomedical applications

The successful applications of magnesium-based alloys as biodegradable orthopedic implants are mainly inhibited due to their high degradation rates in physiological environment. This study examines the bio-corrosion behaviour of Mg–2Zn–0.2X (X = Ca, Mn, Si) alloys in Ringer’s physiological solution that simulates bodily fluids, and compares it with that of AZ91 magnesium alloy. Potentiodynamic polarization and electrochemical impedance spectroscopy results showed a better corrosion behaviour of AZ91 alloy with respect to Mg–2Zn–0.2Ca and Mg–2Zn–0.2Si alloys. On the contrary, enhanced corrosion resistance was observed for Mg–2Zn–0.2Mn alloy compared to the AZ91 one: Mg–2Zn–0.2Mn alloy exhibited a four-fold increase in the polarization resistance than AZ91 alloy after 168 h exposure to the Ringer’s physiological solution. The improved corrosion behaviour of the Mg–2Zn–0.2Mn alloy with respect to the AZ91 one can be ascribed to enhanced protective properties of the Mg(OH)₂ surface layer. The present study suggests the Mg–2Zn–0.2Mn alloy as a promising candidate for its applications in degradable orthopedic implants, and is worthwhile to further investigate the in vivo corrosion behaviour as well as assessed the mechanical properties of this alloy.     

Surface treatments for controlling corrosion rate of biodegradable Mg and Mg-based alloy implants

Due to their excellent biodegradability characteristics, Mg and Mg-based alloys have become an emerging material in biomedical implants, notably for repair of bone as well as coronary arterial stents. However, the main problem with Mg-based alloys is their rapid corrosion in aggressive environments such as human bodily fluids. Previously, many approaches such as control of alloying materials, composition and surface treatments, have been attempted to regulate the corrosion rate. This article presents a comprehensive review of recent research focusing on surface treatment techniques utilised to control the corrosion rate and surface integrity of Mg-based alloys in both in vitro and in vivo environments. Surface treatments generally involve the controlled deposition of thin film coatings using various coating processes, and mechanical surfacing such as machining, deep rolling or low plasticity burnishing. The aim is to either make a protective thin layer of a material or to change the micro-structure and mechanical properties at the surface and sub-surface levels, which will prevent rapid corrosion and thus delay the degradation of the alloys. We have organised the review of past works on coatings by categorising the coatings into two classes—conversion and deposition coatings—while works on mechanical treatments are reviewed based on the tool-based processes which affect the sub-surface microstructure and mechanical properties of the material. Various types of coatings and their processing techniques under two classes of coating and mechanical treatment approaches have been analysed and discussed to investigate their impact on the corrosion performance, biomechanical integrity, biocompatibility and cell viability. Potential challenges and future directions in designing and developing the improved biodegradable Mg/Mg-based alloy implants were addressed and discussed. The literature reveals that no solutions are yet complete and hence new and innovative approaches are required to leverage the benefit of Mg-based alloys. Hybrid treatments combining innovative biomimetic coating and mechanical processing would be regarded as a potentially promising way to tackle the corrosion problem. Synergetic cutting-burnishing integrated with cryogenic cooling may be another encouraging approach in this regard. More studies focusing on rigorous testing, evaluation and characterisation are needed to assess the efficacy of the methods.     

Surface treatments for controlling corrosion rate of biodegradable Mg and Mg-based alloy implants

Abstract

Due to their excellent biodegradability characteristics, Mg and Mg-based alloys have become an emerging material in biomedical implants, notably for repair of bone as well as coronary arterial stents. However, the main problem with Mg-based alloys is their rapid corrosion in aggressive environments such as human bodily fluids. Previously, many approaches such as control of alloying materials, composition and surface treatments, have been attempted to regulate the corrosion rate. This article presents a comprehensive review of recent research focusing on surface treatment techniques utilised to control the corrosion rate and surface integrity of Mg-based alloys in both in vitro and in vivo environments. Surface treatments generally involve the controlled deposition of thin film coatings using various coating processes, and mechanical surfacing such as machining, deep rolling or low plasticity burnishing. The aim is to either make a protective thin layer of a material or to change the micro-structure and mechanical properties at the surface and sub-surface levels, which will prevent rapid corrosion and thus delay the degradation of the alloys. We have organised the review of past works on coatings by categorising the coatings into two classes—conversion and deposition coatings—while works on mechanical treatments are reviewed based on the tool-based processes which affect the sub-surface microstructure and mechanical properties of the material. Various types of coatings and their processing techniques under two classes of coating and mechanical treatment approaches have been analysed and discussed to investigate their impact on the corrosion performance, biomechanical integrity, biocompatibility and cell viability. Potential challenges and future directions in designing and developing the improved biodegradable Mg/Mg-based alloy implants were addressed and discussed. The literature reveals that no solutions are yet complete and hence new and innovative approaches are required to leverage the benefit of Mg-based alloys. Hybrid treatments combining innovative biomimetic coating and mechanical processing would be regarded as a potentially promising way to tackle the corrosion problem. Synergetic cutting-burnishing integrated with cryogenic cooling may be another encouraging approach in this regard. More studies focusing on rigorous testing, evaluation and characterisation are needed to assess the efficacy of the methods.     

Recent advances in biodegradation controls over Mg alloys for bone fracture management: A review

Magnesium (Mg) alloys possess comparable physical and mechanical properties to bone, making them an outstanding candidate of implant materials for bone fracture treatment. In addition to the excellent biocompatibility, and bioactivity, the engagement of Mg alloys is key for a number of biological functionalities in the human body. The unique biodegradation nature of Mg alloy implants implies that it may not require a secondary removal procedure when the expected supporting tasks accomplish, as they may simply and safely “disappear” over time. Nonetheless, the demonstrated drawback of potentially rapid degradation, is an issue that must be addressed appropriately for Mg implants and is consequently given unique attention in this review article. Herein, the critical criteria and the state-of-the-art strategies for controlling the degradation process of Mg alloys are reported. Furthermore, future developments of biodegradable Mg and its alloys systems with satisfactory specifications for clinical trials and deployment, are discussed. This review aims to provide information to materials scientists and clinical practitioners in the context of developing practical biodegradable Mg alloys.     

In vitro degradation behavior and biocompatibility of Mg–Nd–Zn–Zr alloy by hydrofluoric acid treatment

In this paper, Mg–Nd–Zn–Zr alloy (denoted as JDBM) coated with hydrofluoric acid (HF) chemical conversion film (MgF₂) was researched as a potential biodegradable cardiovascular stent material. The microstructures, in vitro degradation and biocompatibility were investigated. The field emission scanning electron microscopy (FE-SEM) and X-ray photoelectron spectroscopy (XPS) showed that a compact MgF₂ film was formed on the surface of JDBM. The corrosion rate decreased in artificial plasma from 0.337 to 0.253 mm·y^? 1 and the electrochemical measurement demonstrated that the corrosion resistance of JDBM alloy could be obviously improved due to the protective MgF₂ film on the surface of the substrate. Meanwhile, the hemolysis ratio of JDBM decreased from 52.0% to 10.1% and the cytotoxicity met the requirement of cellular application after HF treatment. In addition, JDBM and MgF₂ film showed good anti-platelet adhesion, which is a very favorable property for implant material in contact with blood directly.     

Effect of minor content of Gd on the mechanical and degradable properties of as-cast Mg-2Zn-xGd-0.5Zr alloys

RE-containing Mg alloys used as biodegradable medical implants exhibit good promising application due to their good mechanical properties and degradation resistance. In this work, effect of Gd on the microstructure, mechanical properties and biodegradation of as-cast Mg-2Zn-xGd-0.5Zr alloys was investigated. The results showed that there were mainly α-Mg, I-phase, W-phase and MgZn2 phase in Mg-Zn-Gd-Zr alloys. With increase of the Gd content, the strength of the alloys was enhanced due to the second phase strengthening and grain refinement. The degradation resistance of Mg-2Zn-0.5Zr alloy was increased by adding 0.5%–1% Gd due to the uniformly distributed second phases which acted as a barrier to prevent the pitting corrosion. However, increasing Gd content to 2% reduced the degradation resistance of the alloy due to the galvanic corrosion between the matrix and the second phases.The good degradation resistance and mechanical properties of as-cast Mg-2Zn-1Gd-0.5Zr alloy makes it outstanding for biomaterial application.     

Mechanical and bio-corrosion properties of quaternary Mg–Ca–Mn–Zn alloys compared with binary Mg–Ca alloys

Binary Mg–xCa alloys and the quaternary Mg–Ca–Mn–xZn were studied to investigate their bio-corrosion and mechanical properties. The surface morphology of specimens was characterized by X-ray diffraction (XRD), Fourier-transformed infrared spectroscopy (FTIR), scanning electron microscopy (SEM) and energy dispersive X-ray spectroscopy (EDS). The results of mechanical properties show that the yield strength (YS), ultimate tensile strength (UTS) and elongation of quaternary alloy increased significantly with the addition of zinc (Zn) up to 4 wt.%. However, further addition of Zn content beyond 4 wt.% did not improve yield strength and ultimate tensile strength. In contrast, increasing calcium (Ca) content has a deleterious effect on binary Mg–Ca alloys. Compression tests of the magnesium (Mg) alloys revealed that the compression strength of quaternary alloy was higher than that of binary alloy. However, binary Mg–Ca alloy showed higher reduction in compression strength after immersion in simulated body fluid. The bio-corrosion behaviour of the binary and quaternary Mg alloys were investigated using immersion tests and electrochemical tests. Electrochemical tests shows that the corrosion potential (E_corr) of binary Mg–2Ca significantly shifted toward nobeler direction from −1996.8 to −1616.6 mV_SCE with the addition of 0.5 wt.% manganese (Mn) and 2 wt.% Zn content. However, further addition of Zn to 7 wt.% into quaternary alloy has the reverse effect. Immersion tests show that the quaternary alloy accompanied by two secondary phases presented higher corrosion resistance compared to binary alloys with single secondary phase. The degradation behaviour demonstrates that Mg–2Ca–0.5Mn–2Zn alloy had the lowest degradation rate among quaternary alloys. In contrast, the binary Mg–2Ca alloy demonstrated higher corrosion rates, with Mg–4Ca alloy having the highest rating. Our analysis showed the Mg–2Ca–0.5Mn–2Zn alloy with suitable mechanical properties and excellent corrosion resistance can be used as biodegradable implants.     

Towards biodegradable wireless implants

A new generation of partially or even fully biodegradable implants is emerging. The idea of using temporary devices is to avoid a second surgery to remove the implant after its period of use, thereby improving considerably the patient's comfort and safety. This paper provides a state-of-the-art overview and an experimental section that describes the key technological challenges for making biodegradable devices. The general considerations for the design and synthesis of biodegradable components are illustrated with radiofrequency-driven resistor-inductor-capacitor (RLC) resonators made of biodegradable metals (Mg, Mg alloy, Fe, Fe alloys) and biodegradable conductive polymer composites (polycaprolactone-polypyrrole, polylactide-polypyrrole). Two concepts for partially/fully biodegradable wireless implants are discussed, the ultimate goal being to obtain a fully biodegradable sensor for in vivo sensing.     

Surface Modification on Biodegradable Magnesium Alloys as Orthopedic Implant Materials to Improve the Bio-adaptability:A Review

Magnesium(Mg) and its alloys as a novel kind of biodegradable material have attracted much fundamental research and valuable exploration to develop its clinical application. Mg alloys degrade too fast at the early stage after implantation, thus commonly leading to some problems such as osteolysis, early fast mechanical loss, hydric bubble aggregation, gap formation between the implants and the tissue. Surface modification is one of the effective methods to control the degradation property of Mg alloys to adapt to the need of organism. Some coatings with bioactive elements have been developed, especially for the micro-arc oxidation coating, which has high adhesion strength and can be added with Ca, P, and Sr elements. Chemical deposition coating including bio-mimetic deposition coating, electro-deposition coating and chemical conversion coating can provide good anticorrosion property as well as better bioactivity with higher Ca and P content in the coating. From the biodegradation study, it can be seen that surface coating protected the Mg alloys at the early stage providing the Mg alloy substrate with lower degradation rate. The biocompatibility study showed that the surface modification could provide the cell and tissue stable and weak alkaline surface micro-environment adapting to the cell adhesion and tissue growth.The surface modification also decreased the mechanical loss at the early stage adapting to the loadbearing requirement at this stage. From the interface strength between Mg alloys implants and the surrounding tissue study, it can be seen that the surface modification improved the bio-adhesion of Mg alloys with the surrounding tissue, which is believed to be contributed to the tissue adaptability of the surface modification. Therefore, the surface modification adapts the biodegradable magnesium alloys to the need of biodegradation, biocompatibility and mechanical loss property. For the different clinical application, different surface modification methods can be provided to adapt to the clinical requirements for the Mg alloy implants.     

Corrosion studies of modified organosilane coated magnesium–yttrium alloy in different environments

Magnesium (Mg) and its alloys have numerous potential applications as biodegradable implants, but the fast degradation rate of Mg alloys at the initial implanted stage could be a problem. This paper describes the modification of the water-based bis-[triethoxysilyl] ethane (BTSE) silane applied to the surface of magnesium–yttrium (Mg–4Y) to increase its corrosion resistance. Surface characterization by SEM, FTIR, and EDX showed that the hydrolysis and condensation of the silane resulted in a covalent bonding to the Mg–4Y surface. Corrosion behavior of the uncoated and coated Mg–4Y alloy was evaluated in different environments by using a novel self-developed corrosion probe. Based on the electrochemical results of DC polarization and electrochemical impedance spectroscopy (EIS), we conclude that the epoxy-modified BTSE silane coating successfully increases the corrosion resistance at the initial stage of implantation. The corrosion rates in the flesh of dead mice environments such as body cavity and subcutaneous tissue of the mice were lower than the corrosion rates in in vitro environments.     

Improvement of <Emphasis Type="Italic">in vitro</Emphasis> behavior of an Mg alloy using a nanostructured composite bioceramic coating

Magnesium (Mg) alloys as a new group of biodegradable metal implants are being extensively investigated as a promising selection for biomaterials applications due to their apt mechanical and biological performance. However, as a foremost drawback of Mg alloys, the high degradation in body fluid prevents its clinical applications. In this work, a bioceramic composite coating is developed composed of diopside, bredigite, and fluoridated hydroxyapatite on the AZ91 Mg alloy in order to moderate the degradation rate, while improving its bioactivity, cell compatibility, and mechanical integrity. Microstructural studies were performed using a transmission electron microscope (TEM), scanning electron microscope (SEM), X-ray diffraction (XRD) analysis, and energy dispersive spectroscopy (EDS). The degradation properties of samples were carried out under two steps, including electrochemical corrosion test and immersion test in simulated body fluid (SBF). Additionally, compression test was performed to evaluate the mechanical integrity of the specimens. L-929 fibroblast cells were cultured on the samples to determine the cell compatibility of the samples, including the cell viability and attachment. The degradation results suggest that the composite coating decreases the degradation and improves the bioactivity of AZ91 Mg alloy substrate. No considerable deterioration in the compression strength was observed for the coated samples compared to the uncoated sample after 4 weeks immersion. Cytotoxicity test indicated that the coatings improve the cell compatibility of AZ91 alloy for L-929 cells.     

Fabrication of Mg alloy tubes for biodegradable stent application

Though Mg alloys are promising candidates for biodegradable stents, it is very difficult to fabricate stent tubes with high dimensional accuracy using Mg alloys because of their low deformability. This study aimed to develop thin-walled, high-quality Mg alloy tubes with good performance in stent applications. Cold drawing with a fixed mandrel was carried out for extruded Mg-0.8%Ca and AZ61 alloy tubes using optimized drawing parameters and lubrication, and stent tubes with 1.5–1.8 mm outer diameter and 150 μm thickness were fabricated. A dimensional evaluation showed that the tube dimensional errors were within 0.02–2.5%. Also, an immersion test of pure Mg with different crystal orientations showed that the crystal orientation affected the corrosion properties, results that are the same with other Mg alloys. The crystal orientation of the stent tube could be controlled by changing the deformation amount and direction in the drawing, showing that it is possible to further improve the biodegradability of stents by approaching their fabrication from a processing aspect.     

Preparation and characterization of as-extruded Mg–Sn alloys for orthopedic applications

In this study, as-extruded Mg–Sn alloys with various Sn content were prepared and characterized for orthopedic applications. The results of microstructure observations and X-ray diffraction analysis showed that as-extruded Mg–Sn alloys were composed of α-Mg and Mg₂Sn phases, and the content of Mg₂Sn phase increased with increasing Sn content. The microstructure of as-extruded Mg–Sn alloy with 1 wt.% Sn was equiaxed grain, while the one with a higher Sn content was inhomogeneous microstructure and the grain size of the long elongated grains decreased with increasing Sn content. Tensile test revealed that the yield strength and ultimate tensile strength of as-extruded Mg–Sn alloys increased while the elongation decreased with increasing Sn content. Immersion and electrochemical tests indicated that the microstructure of as-extruded Mg–Sn alloys affected their corrosion properties, and the increase of Mg₂Sn phase resulted from the increase of the Sn content led to a higher corrosion rate. The cytotoxicity test showed that as-extruded Mg–1Sn and Mg–3Sn alloys met the requirement of cell toxicity for orthopedic applications. Our analyses showed that as-extruded Mg–1Sn and Mg–3Sn alloys were promising to be used as biodegradable orthopedic implants.     

Design and characterizations of novel biodegradable ternary Zn-based alloys with IIA nutrient alloying elements Mg,Ca and Sr

Apart from the industrial and automotive applications, Zn and Zn-based alloys are considered as a new kind of potential biodegradable material quite recently. However, one drawback of pure Zn as potential biodegradable metal lies in that pure Zn has quite low strength and plasticity. In the present study, three important IIA essential nutrient elements Mg, Ca and Sr and hot-rolling and hot-extrusion thermal deformations have been applied to overcome the drawback of pure Zn and benefit the biocompatibility of Zn-based potential implants. The microstructure, mechanical properties, corrosion behavior, hemocompatibility, in vitro cytocompatibility were studied systematically to investigate their feasibility as bioabsorbable implants. The results showed that the mechanical properties of the ternary Zn–1Mg–1Ca, Zn–1Mg–1Sr and Zn–1Ca–1Sr alloys are much higher than that of pure Zn, owing to both the alloying effects and thermal deformation effects. In vitro hemolytic rate test and cell viability test indicated that the addition of the IIA nutrient alloying elements Mg, Ca and Sr into Zn can benefit their hemocompatibility and cytocompatibility, which would further guarantee the biosafety of these new kind of biodegradable Zn-based implants for future clinical applications.