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.     

Surface Engineering of Biodegradable Magnesium Alloys for Enhanced Orthopedic Implants

Magnesium (Mg) alloys have been promised for biomedical implants in orthopedic field, however, the fast corrosion rate and mode challenge their clinical application. To push Mg alloys materials into practice, a composite coating with biodegradable and high compatible components to improve anticorrosion property of an Mg alloy (i.e., AZ31) is designed and fabricated. The inner layer is micro‐nano structured Mg(OH)₂ through hydrothermal treatment. Then stearic acid (SA) is introduced to modify Mg(OH)₂ for better reducing the gap below a surface‐degradation polymer layer of poly(1,3‐trimethylene carbonate). Benefited by the SA modification effect, this sandwiched coating avoids corrosive medium penetration via enhancing the adhesion strength at the interface between outer and inner layers. Both in vitro and in vivo tests indicate that the composite coating modified AZ31 perform a better anticorrosion behavior and biocompatibility compared to bare AZ31. Strikingly, a 1.7‐fold improvement in volume of newly formed bone is observed surrounding the composite coating modified implant after 12 week implantation. The sandwiched biocompatible coating strategy paves a hopeful way for future translational application of Mg alloys orthopedic materials in clinics.     

Challenges and Solutions for the Additive Manufacturing of Biodegradable Magnesium Implants

Due to their capability of fabricating geometrically complex structures, additive manufacturing (AM) techniques have provided unprecedented opportunities to produce biodegradable metallic implants—especially using Mg alloys, which exhibit appropriate mechanical properties and outstanding biocompatibility. However, many challenges hinder the fabrication of AM-processed biodegradable Mg-based implants, such as the difficulty of Mg powder preparation, powder splash, and crack formation during the AM process. In the present work, the challenges of AM-processed Mg components are analyzed and solutions to these challenges are proposed. A novel Mg-based alloy (Mg–Nd–Zn–Zr alloy, JDBM) powder with a smooth surface and good roundness was first synthesized successfully, and the AM parameters for Mg-based alloys were optimized. Based on the optimized parameters, porous JDBM scaffolds with three different architectures (biomimetic, diamond, and gyroid) were then fabricated by selective laser melting (SLM), and their mechanical properties and degradation behavior were evaluated. Finally, the gyroid scaffolds with the best performance were selected for dicalcium phosphate dihydrate (DCPD) coating treatment, which greatly suppressed the degradation rate and increased the cytocompatibility, indicating a promising prospect for clinical application as bone tissue engineering scaffolds.     

生物医用可降解锌基合金的研究进展

锌基合金是近几年新兴的一种医用可降解材料,有望应用于心血管支架及骨植入等医疗器械。锌是人体必需的营养元素,具有良好的生物相容性及适宜的体内降解速率,作为可降解合金的基体有很广的应用前景。然而,生物可降解锌基合金的设计、加工、强化及降解机理等研究尚处于起步阶段,还需要做大量的基础研究工作。本文以最终医疗器械产品的理想标准要求为切入点,从生物相容性、力学性能及抗腐蚀性能等方面对近几年医用锌基合金的研究成果进行了综述分析,并展望了其未来的发展方向。     

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.     

Cytocompatibility evaluation of different biodegradable magnesium alloys with human mesenchymal stem cells

In the last few years, the use of biodegradable magnesium (Mg) alloys has evoked great interest in the orthopedic field due to great advantages over long-term implant materials associated with various side effects like allergy and sensitization and consequent implant removal surgeries. However, degradation of these Mg alloys results in ion release, which may cause severe cytotoxicity and undesirable complications after implantation. In this study, we investigated the cytological effects of various Mg alloys on cells that play an important role in bone repair. Eight different magnesium alloys containing varying amounts of Al, Zn, Nd and Y were either incubated directly or indirectly with the osteosarcoma cell line Saos-2 or with uninduced and osteogenically-induced human mesenchymal stem cells (MSCs) isolated from bone marrow specimens obtained from the femoral shaft of patients undergoing total hip replacement. Cell viability, cell attachment and the release of ions were investigated at different time points in vitro. During direct or indirect incubation different cytotoxic effects of the Mg alloys on Saos-2 cells and osteogenically-induced or uninduced MSCs were observed. Furthermore, the concentration of degradation products released from the Mg alloys differed. Overall, Mg alloys MgNd2, MgY4, MgAl9Zn1 and MgY4Nd2 exhibit good cytocompatibility. In conclusion, this study reveals the necessity of cytocompatibility evaluation of new biodegradable magnesium alloys with cells that will get in direct contact to the implant material. Furthermore, the use of standardized experimental in vitro assays is necessary in order to reliably and effectively characterize new Mg alloys before performing in vivo experiments.     

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.     

A preliminary study for novel use of two Mg alloys (WE43 and Mg3Gd)

In this study, two types of magnesium alloys (WE43 and Mg3Gd) were compared with Heal-All membrane (a biodegradable membrane used in guided bone regeneration) in vitro to determine whether the alloys could be used as biodegradable membranes. Degradation behavior was assessed using immersion testing with simulated body fluid (SBF). Microstructural characteristics before and after immersion were evaluated through scanning electron microscopy, and degradation products were analyzed with energy dispersive spectrometry (EDS). To evaluate the biocompatibility of the three types of materials, we performed cytotoxicity, adhesion, and mineralization tests using human osteoblast-like MG63 cells. Immersion testing results showed no significant difference in degradation rate between WE43 and Mg3Gd alloys. However, both Mg alloys corroded faster than the Heal-All membrane, with pitting corrosion as the main corrosion mode for the alloys. Degradation products mainly included P- and Ca-containing apatites on the surface of WE43 and Mg3Gd, whereas these apatites were rarely detected on the surface of the Heal-All membrane. All three type of materials exhibited good biocompatibility. In the mineralization experiment, the alkaline phosphatase (ALP) activity of 10 % Mg3Gd extract was significantly higher than the extracts of the two other materials and the negative control. This study highlighted the potential of these Mg-REE alloys for uses in bone regeneration and further studies and refinements are obviously required.     

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.     

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.     

Fundamentals and advances in magnesium alloy corrosion

There remains growing interest in magnesium (Mg) and its alloys, as they are the lightest structural metallic materials. Mg alloys have the potential to enable design of lighter engineered systems, including positive implications for reduced energy consumption. Furthermore, Mg alloys are also emerging as viable biodegradable materials and battery electrodes. In spite of the greatest historical Mg usage at present, the wider use of Mg alloys remains restricted by a number of inherent limitations, including vulnerability to corrosion, poor formability and low creep resistance. This review covers recent research that has led to advances in Mg-alloy corrosion; including the application of contemporary methods for understanding Mg corrosion, the establishment of an electrochemical framework for Mg corrosion, illumination of alloying effects, and attempts at corrosion resistant Mg alloys. A discussion drawing from many sources provides an unbiased focus on new achievements, as well as some contentious issues in the field. The electrochemistry of Mg is reviewed in detail, including so-called anodic hydrogen evolution and cathodic activation. This review also covers atmospheric corrosion, and biodegradable Mg alloys. Finally, past and present trends in the field of Mg corrosion are reviewed, identifying knowledge gaps, whilst attempting to also identify future developments and directions.     

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.     

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.     

Effects of Li addition on the corrosion behaviour and biocompatibility of Mg(Li)–Zn–Ca metallic glasses

Magnesium alloys with suitable corrosion behaviour and good mechanical properties are desired for biodegradable materials. In the current study, novel Mg–Li-based metallic glasses (MGs) demonstrate potential clinical applications as implantable biodegradable materials. The amorphous structure of MGs provides suitable elastic modulus with human bone. The enhanced corrosion resistance of MGs realises a uniform corrosion process, as well as maintains a stable acid-based environment, and increases cell proliferation. A schematic model is proposed to illustrate the corrosion mechanisms of MGs. Adding Li significantly improves the corrosion resistance of MGs. Both the indirect cytotoxicity and direct cell culture assays are conducted using transfected osteoblasts (hFOB) cells. Results show that the novel Mg–Li–Zn–Ca MGs have good biocompatibility.     

Monetite and brushite coated magnesium: in vivo and in vitro models for degradation analysis

The use of magnesium (Mg) as a biodegradable metallic replacement of permanent orthopaedic materials is a current topic of interest and investigation. The appropriate biocompatibility, elastic modulus and mechanical properties of Mg recommend its suitability for bone fracture fixation. However, the degradation rates of Mg can be rapid and unpredictable resulting in mass hydrogen production and potential loss of mechanical integrity. Thus the application of calcium phosphate coatings has been considered as a means of improving the degradation properties of Mg. Brushite and monetite are utilized and their degradation properties (alongside uncoated Mg controls) are assessed in an in vivo subcutaneous environment and the findings compared to their in vitro degradation behaviour in immersion tests. The current findings suggest monetite coatings have significant degradation protective effects compared to brushite coatings in vivo. Furthermore, it is postulated that an in vitro immersion test may be used as a tentative predictor of in vivo subcutaneous degradation behavior of calcium phosphate coated and uncoated Mg.     

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.     

A review on biodegradable materials for cardiovascular stent application

A stent is a medical device designed to serve as a temporary or permanent internal scaffold to maintain or increase the lumen of a body conduit. The researchers and engineers diverted to investigate biodegradable materials due to the limitation of metallic materials in stent application such as stent restenosis which requires prolonged anti platelet therapy, often result in smaller lumen after implantation and obstruct re-stenting treatments. Biomedical implants with temporary function for the vascular intervention are extensively studied in recent years. The rationale for biodegradable stent is to provide the support for the vessel in predicted period of time and then degrading into biocompatible constituent. The degradation of stent makes the re-stenting possible after several months and also ameliorates the vessel wall quality. The present article focuses on the biodegradable materials for the cardiovascular stent. The objective of this review is to describe the possible biodegradable materials for stent and their properties such as design criteria, degradation behavior, drawbacks and advantages with their recent clinical and preclinical trials.     

Gas formation and biological effects of biodegradable magnesium in a preclinical and clinical observation

Magnesium alloys are biodegradable metals receiving increasing attention, but the clinical applications of these materials are delayed by concerns over the rapid corrosion rate and gas formation. Unlike corrosion, which weakens mechanical properties, the gas formation issue has received little attention. Therefore, we evaluated the gas formation and biological effects for Mg implants through preclinical (immersed in Earle’s balanced salt solution and in vivo) and clinical studies. The immersion test examined the gas volume and composition. The in vivo study also examined gas volume and histological analysis. The clinical study examined the gas volume and safety after Mg screw metatarsal fixation. Gas was mainly composed of H₂, CO and CO₂. Maximum volumes of gas formed after 5 days for in vivo and 7 days in clinical study. Within the clinical examination, two superficial wound complications healed with local wound care. Osteolytic lesions in the surrounding metaphysis of the Mg screw insertion developed in all cases and union occurred at 3 months. Mg implants released gas with variable volumes and composition (H₂, CO, and CO₂), with no long-term toxic effects on the surrounding tissue. The implants enabled bone healing, although complications of wound breakdown and osteolytic lesions developed.     

PHB,crystalline and amorphous magnesium alloys: Promising candidates for bioresorbable osteosynthesis implants?

In this study various biodegradable materials were tested for their suitability for use in osteosynthesis implants, in particular as elastically stable intramedullary nails for fracture treatment in paediatric orthopaedics. The materials investigated comprise polyhydroxybutyrate (PHB), which belongs to the polyester family and is produced by microorganisms, with additions of ZrO₂ and a bone graft substitute; two crystalline magnesium alloys with significantly different degradation rates ZX50 (MgZnCa, fast) and WZ21 (MgYZnCa, slow); and MgZnCa bulk metallic glasses (BMG). Push-out tests were conducted after various implantation times in rat femur meta-diaphysis to evaluate the shear forces between the implant material and the bone. The most promising materials are WZ21 and BMG, which exhibit high shear forces and push-out energies. The degradation rate of ZX50 is too fast and thus the alloy does not maintain its mechanical stability long enough during the fracture-healing period. PHB exhibits insufficient mechanical properties: it degrades very slowly and the respective low shear forces and push-out energy levels are unsatisfactory.