Elsevier

Acta Biomaterialia

Volume 11, 1 January 2015, Pages 554-562
Acta Biomaterialia

Effect of the addition of low rare earth elements (lanthanum, neodymium, cerium) on the biodegradation and biocompatibility of magnesium

https://doi.org/10.1016/j.actbio.2014.09.041Get rights and content

Abstract

Rare earth elements are promising alloying element candidates for magnesium alloys used as biodegradable devices in biomedical applications. Rare earth elements have significant effects on the high temperature strength as well as the creep resistance of alloys and they improve magnesium corrosion resistance. We focused on lanthanum, neodymium and cerium to produce magnesium alloys with commonly used rare earth element concentrations. We showed that low concentrations of rare earth elements do not promote bone growth inside a 750 μm broad area around the implant. However, increased bone growth was observed at a greater distance from the degrading alloys. Clinically and histologically, the alloys and their corrosion products caused no systematic or local cytotoxicological effects. Using microtomography and in vitro experiments, we could show that the magnesium–rare earth element alloys showed low corrosion rates, both in in vitro and in vivo. The lanthanum- and cerium-containing alloys degraded at comparable rates, whereas the neodymium-containing alloy showed the lowest corrosion rates.

Introduction

One of the actual and much-needed demands in orthopaedics is the clinical availability of biodegradable implants [1], [2], [3], [4], [5]. In some clinical applications, such as fracture treatment, permanent metal implants are not necessary or even disadvantageous and a temporary implant concept would be much more suitable. Temporary implants made of biodegradable materials are destined to corrode and dissolve postoperatively and hence a second surgery for implant removal is not necessary, eliminating surgery and accompanied additional costs and unnecessary health risks for the patients. The requirements for such temporary implants are multi-fold and depend upon the site of their utilization. However, some properties are essential: (i) the material should provide a controlled and adequate degradation profile, whilst allowing (ii) necessary spatial and temporal mechanical stability. (iii) The biodegradable material or its components should not only be biocompatible [6], [7], but moreover, (iv) it should at best assist specific and desired biological effects such as stimulating regeneration, healing processes or supporting anti-inflammatory mechanisms. (v) Finally and optimally, the biodegradable material should be completely replaced by host tissue. Amongst other candidates, magnesium-based alloys are very promising materials for such temporary implants [4], [8], [9]. These alloys offer some remarkable physico-chemical properties [10], [11], [12], [13], [14] while they disintegrate gradually up to complete dissolution in physiological environments. Magnesium and its alloys show high degrees of biocompatibility [15], [16], [17], [18], [19] and very interestingly, an increased bone growth has been repeatedly reported in the vicinity of corroding magnesium implants or its corrosion products [20], [21], [22], [23]. Actually, a drug-eluting magnesium stent [24] and a magnesium screw consisting of MgYREZr (a material similar to WE43) that contains >90 wt.% magnesium [25] are already in clinical use.

Despite the remarkable progress which was achieved in the development of Mg-based alloys, the important issues of corrosion resistance, gas formation, biocompatibility and mechanical stability need more research effort. In our search of suitable alloying elements for biomedically usable magnesium alloys, we concentrated on cerium (Ce), lanthanum (La) and neodymium (Nd), three rare earth elements (REEs). REE are widely used in different commercially available alloys such as AE, QE, WE or ZE series alloys [26], [27], [28]. The addition of REEs has significant effects on the high temperature strength and creep resistance [29] and they improve magnesium corrosion resistance [30]. For engineering applications, REEs are usually added as a mischmetal of various compositions commonly rich in Ce, La and Nd; however, this mischmetal can vary in its composition depending on its source. For biomedical applications a more defined approach is desirable, since reproducibility is a major requirement for medical devices. In a first approach, we focused on the collectivity of eligible REEs on these commonly occurring three elements and we prepared Mg–Ce, Mg–La and Mg–Nd alloys to observe the in vitro and in vivo effects. The alloy compositions were used at a concentration which was determined from an average of the most common representatives of Mg–REE alloys, e.g. 2.0–2.5% neodymium was used for WE43A alloy, according to ASTM B275-04 [31], [32]. We expected these concentrations to be toxicologically noncritical but sufficient enough to influence positively the mechanical properties of the alloy matrix architecture.

This study investigated the microstructures, the in vitro corrosion behaviour and the cytotoxicity of low concentrations of REE in Mg alloys. To observe the effects of these different Mg–REE alloys on the reactions of bone tissue, they were implanted, within the limits of a pilot study, into rabbit femur condyles. General biocompatibility as well as changes in the surrounding tissues using histomorphological analysis was investigated.

Section snippets

Preparation of Mg–REE alloys and microstructure observation

Three binary Mg–REE alloys (Mg–Ce: 1.27 wt.% cerium; Mg–La: 0.69 wt.% lanthanum; Mg–Nd: 2.13 wt.% neodymium) were melted and cast in pure Mg (99.95%) and commercially pure REE under a mixed gas atmosphere of SF6 and CO2 using a mild steel crucible. The chemical compositions of Mg–REE alloys were measured by inductively coupled plasma atomic emission spectrometry (Profile ICP-AES, Leeman Labs, Husdon, USA). The cylindrical samples (3 mm diameter and 5 mm height) were cut from casting ingots and

Microstructures of Mg–REE alloys

The typical microstructures of the as-cast Mg–Ce (Fig. 1a), Mg–La (Fig. 1b) and Mg–Nd (Fig. 1c) alloys showed coarse grains and bright intermetallic phases. The intermetallics distributed at the grain boundaries and inner grains, identified as RE-rich precipitate by EDS analysis (Fig. 1d). XRD examination indicated that the intermetallic phases in Mg–Ce, Mg–La and Mg–Nd alloys were identified as Mg12Ce, Mg17La2 and Mg12Nd (data not shown). The intermetallic volume percentage of the three alloys

Discussion

In this study, the three Mg–REE alloys exhibited quite different corrosion behaviours in the corrosion tests, both in vitro and in vivo. The typical microstructures of the as-cast Mg–REE alloys showed coarse grains and bright intermetallic phases identified as REE-rich precipitates. Similar results were obtained in previous studies referring to as-cast binary Mg–Ce and Mg–Nd alloys [11], [37], [38]. However, the intermetallic in Mg–La was identified as Mg17La2, which was different from the

Conclusion

This paper demonstrates that Mg–La exhibits the highest corrosion rate in vitro, followed by Mg–Ce and Mg–Nd alloys. The Mg–Nd alloy also appears to have the lowest corrosion rate in vivo. In addition, Mg–Ce showed more severe cytotoxicity to MC3T3-E1 cells than Mg–La and Mg–Nd. All tested Mg–REE (Mg–Ce, Mg–La and Mg–Nd) corroded slowly in vivo without enhancing bone growth in a 750 μm broad tissue area around the implant.

Disclosures

The authors declare no conflicts of interest.

Acknowledgements

This work was supported by the National Basic Research Program of China (973 Program) (Grant Nos. 2012CB619102 and 2012CB619100), National Science Fund for Distinguished Young Scholars (Grant No. 51225101). We thank Michael Schwarze for help with statistical analysis, Sean Lynch for critical reading of the manuscript and Maike Haupt, Sophie Müller, and Mattias Reebmann (all from Hannover Medical School) for excellent technical support.

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    1

    These authors contributed equally to this work.

    2

    Present address: Julius Wolff Institute and Center for Musculoskeletal Surgery, Berlin-Brandenburg Center for Regenerative Therapies, Charité-Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany.

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