Novel Magnesium Alloys Developed for Biomedical Application: A Review

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There is an increasing interest in the development of magnesium alloys both for industrial and biomedical applications. Industrial interest in magnesium alloys is based on strong demand of weight reduction of transportation vehicles for better fuel efficiency, so higher strength, and better ductility and corrosion resistance are required. Nevertheless, biomedical magnesium alloys require appropriate mechanical properties, suitable degradation rate in physiological environment, and what is most important, biosafety to human body. Rather than simply apply commercial magnesium alloys to biomedical field, new alloys should be designed from the point of view of nutriology and toxicology. This article provides a review of state-of-the-art of magnesium alloy implants and devices for orthopedic, cardiovascular and tissue engineering applications. Advances in new alloy design, novel structure design and surface modification are overviewed. The factors that influence the corrosion behavior of magnesium alloys are discussed and the strategy in the future development of biomedical magnesium alloys is proposed.

Introduction

Magnesium alloys for biomedical applications are in spotlight recently. They have advantages over traditional metallic materials, ceramics and biodegradable polymers. For mechanical properties, metals are more suitable for load-bearing applications compared with ceramics or polymer because of their high mechanical strength as well as high fracture toughness. The densities of magnesium (1.738 g/cm3) and magnesium alloys (1.75–1.85 g/cm3) are very similar to that of human cortical bone (1.75 g/cm3), while the density of biomedical titanium alloy Ti6Al4V is 4.47 g/cm3[1]. For biocompatibility, magnesium ions are present in large amount in the human body and involved in many metabolic reactions and biological mechanisms. The human body usually contains magnesium approximately 35 g per 70 kg body weight and the daily demand for magnesium is about 375 mg[2]. Magnesium alloys are promising candidates for orthopedic and cardiovascular implants and have attracted increasing attention since there is no requirement for a secondary removal surgery.

Potential of commercial magnesium alloys as biodegradable implant materials were evaluated. Witte et al.[3] investigated in vivo corrosion of 4 magnesium alloys and found that the corrosion layer of all the alloys displayed an accumulation of biological calcium phosphates and all alloys increased the newly formed bone compared to the polymer. According to this study, LAE442 exhibited the lowest corrosion rate, while AZ31, AZ91 and WE43 were found to degrade at similar rates[3]. Gao et al.[4] reported that ZK60 alloy lost 3.1% of its original mass after soaking in a simulated body fluid (SBF) for 242 h, while the mass loss of Mg–5.6Zn–0.55Zr–0.9Y alloy was merely 1.7%, indicating that the addition of the alloying element Y improves the corrosion resistance of ZK60 alloy. Heublein et al.[5] implanted 20 AE21 stents into coronary arteries of 11 domestic pigs. The main limit of the AE21 stents was that their degradation occurred faster than expected as the loss of mechanical integrity occurred between 35 and 56 days after implantation. Then Mario et al.[6] and Peeters et al.[7] reported the results of animal experiment and first clinical study of Lekton Magic coronary stent (Biotronik, Bulach, Switzerland) made from WE43 magnesium alloy, respectively. Based on this Lekton Magic coronary stent, Biotronik Company developed 3 generations of absorbable metal stent (AMS): (1) Studies on clinical implantation of 71 AMS-1 magnesium stents in the coronary arteries of 63 patients showed that the AMS stents can achieve an immediate angiographic result similar to that of other metal stents, and can be safely degraded after 4 months[8]; (2) AMS-2 with new alloy design and stent design maintains longer stent integrity in animal; (3) AMS-3 stent is a Mg alloy stent coated with a fast-degradable polymer carrier with an anti-proliferative drug. The first animal trial in porcine model showed promising results in terms of safety and efficacy compared to bare AMS Mg stent[9].

Although commercial magnesium alloys containing aluminum and/or rare earth elements exhibit good mechanical properties and corrosion resistance, they are not suitable for biomedical applications in consideration of toxicity. Aluminum is well known as a neurotoxicant. The accumulation of Al has been suggested to be associated with various neurological disorders[10]. Severe hepatotoxicity has been detected after the administration of cerium, praseodymium and yttrium[11]. To guarantee the biosafety of biodegradable materials, researchers have developed new type of magnesium alloys, choosing element with no toxicity or low toxicity as alloying elements.

This article reviews the progress and development on biomedical magnesium alloys, mainly on pure Mg, Mg–Ca-based, Mg–Zn-based, Mg–Si-based, Mg–Sr-based and Mg–RE-based alloys. We also discussed novel structure design and surface modification, and proposed the unsolved scientific problems for the future development of biodegradable magnesium alloys.

Section snippets

Purification and Alloying Design of Magnesium for Biomedical Application

Purification and alloying are two strategies to obtain magnesium-based biomaterials with proper properties. Mechanical properties of currently investigated biodegradable magnesium and magnesium alloys are shown in Fig. 1. Fig. 2 shows their corrosion rate and hydrogen evolution rate. Hemolysis rate and effect of magnesium alloy extract on cell viability are summarized in Fig. 3 and Table 1, respectively.

Strategy for Property Adjustment of Biomedical Magnesium Alloys

Besides alloying and processing, there are other approaches that can further adjust properties of magnesium-based biomaterials to realize diverse function and meet the requirement of different implant location. Mechanical properties can be controlled through structure design. Surface treatment is an effective strategy to regulate the degradation rate and the surface properties.

Environmental Factors Influencing Corrosion Behavior of Magnesium

It is very important to understand corrosion mechanism of magnesium implants in vivo and set up a reliable in vitro test bench to estimate the in vivo degradation process. However, previous results of in vitro and in vivo study are in poor correlation between the observed corrosion rates. Magnesium alloys display dramatically faster degradation in vitro[140]. In order to improve the accuracy of in vitro prediction, we should fully understand the factors that influence in vivo degradation of

Concluding Remarks

Development of biodegradable magnesium implants has revolutionized the concept of metallic biomaterials. A qualified magnesium alloy implant should be one of matching corrosion rate with tissue healing rate, sufficient mechanical properties and acceptable biocompatibility. It is challenging but still promising to obtain such new kind of biodegradable metallic implants or devices. Mechanical properties strongly depend on the grain size, the solubility of alloying elements and the size, amount

Acknowledgments

This work was supported by the National Basic Research Program of China (973 Program) (Nos. 2012CB619102 and 2012CB619100), the National Science Fund for Distinguished Young Scholars (No. 51225101), the National Natural Science Foundation of China (No. 31170909), the Research Fund for the Doctoral Program of Higher Education (No. 20100001110011), the Natural Science Foundation of Heilongjiang Province (No. ZD201012), the Project for Supervisor of Excellent Doctoral Dissertation of Beijing (No.

Prof. Yufeng Zheng's research is concerned with development of new kind of biomedical metallic materials, including biodegradable magnesium alloys and iron-based alloys, β-Ti alloys with low elastic modulus, nickel-free Ti-based shape memory alloys, nanocrystalline metals and alloys and bulk metallic glasses, and their medical devices in dentistry, orthopedics and interventional therapy. He has published over 230 SCI journal papers since 1998, with the citation of over 3100 times and h-index of

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    Prof. Yufeng Zheng's research is concerned with development of new kind of biomedical metallic materials, including biodegradable magnesium alloys and iron-based alloys, β-Ti alloys with low elastic modulus, nickel-free Ti-based shape memory alloys, nanocrystalline metals and alloys and bulk metallic glasses, and their medical devices in dentistry, orthopedics and interventional therapy. He has published over 230 SCI journal papers since 1998, with the citation of over 3100 times and h-index of 26. He edited 7 books and book chapters, and owned 27 Chinese Invention Patents. He was granted with over 30 projects including the National Basic Research Program of China and the National Science Fund for Distinguished Young Scholars. He served as a member of the editorial board of Journal of Biomedical Materials Research Part B-Applied Biomaterials (Wiley), the associate editor board of Materials Letters (Elsevier), the editor board of Journal of Materials Science & Technology (Elsevier) and Acta Metallurgica Sinica (English Letters) (Springer).

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