In this work, a bioresorbable Mg-ZKQX6000 (Mg-6Zn-0.6Zr-0.4Ag-0.2Ca (wt%)) alloy was severely plastically deformed via equal channel angular pressing (ECAP) according to three unique hybrid routes at low temperatures (200 degrees C to 125 degrees C). The roles of ECAP processing on microstructure, and ensuing mechanical properties and corrosion rates, are assessed. Microstructurally, ECAP induces a complex plethora of features, especially variations in grain sizes and precipitates' sizes, distributions, and morphologies for individual cases. Mechanically, ECAP generally refined grain size, resulting in ultra-high strength levels of about 400 MPa in ultimate tensile strength for several cases; however, deformation via ECAP of precipitates induced embrittlement and low elongation to failure levels. Corrosion testing, conducted in simulated bodily fluid at bodily pH levels to mimic conditions in the human body, revealed consistent corrosion rates across several techniques (mass loss, hydrogen evolution, and electrochemical impedance spectroscopy (EIS)), showing that severe plastic deformation deteriorates corrosion resistance for this material. In-situ corrosion monitoring explained that corrosion accelerated after ECAP due to the creation of heterogeneous, anodic shear zones, which exhibited dense regions of refined grains and fine precipitates. Suggestions for future design and thermomechanical processing of Mg alloys for bioresorbable orthopedic implants are provided.

Zinc shows great promise as a bio-degradable metal. Our early in vivo investigations implanting pure zinc wires into the abdominal aorta of Sprague-Dawley rats revealed that metallic zinc does not promote restenotic responses and may suppress the activities of inflammatory and smooth muscle cells. However, the low tensile strength of zinc remains a major concern. A cast billet of the Zn-Li alloy was produced in a vacuum induction caster under argon atmosphere, followed by a wire drawing process. Two phases of the binary alloy identified by x-ray diffraction include the zinc phase and intermetallic LiZn4 phase. Mechanical testing proved that incorporating 0.1wt% of Li into Zn increased its ultimate tensile strength from 116±13MPa (pure Zn) to 274±61MPa while the ductility was held at 17±7%. Implantation of 10mm Zn-Li wire segments into abdominal aorta of rats revealed an excellent biocompatibility of this material in the arterial environment. The biodegradation rate for Zn-Li was found to be about 0.008mm/yr and 0.045mm/yr at 2 and 12months, respectively.

Despite innovative surgical techniques and use of current frontal sinus stents from different materials, the problem of treatment failure with consecutive reoperation remains present. The aim of our study is to investigate biocompatibility, degradation kinetics, and functionality of a newly developed fluoride-coated magnesium-based nasal stent. A minipig anatomy of frontal sinus adapted design and an external surgical approach were developed and established. The functionality of the stents was evaluated endoscopically. The stenttissue blocks were analysed after 90 and 180 days using microcomputed tomography (mu-CT), histology, scanning electron microscopy (SEM), and energy-dispersive X-ray spectroscopy (EDS). Functional evaluation revealed an unobstructed stent lumen in all cases. Histological analysis showed moder- ate mucosal hyperplasia with a mild, nonspecific inflammatory response, and nonosteoconductive effect. Rejection reactions or necrosis did not occur. The volumetric analysis of the stents showed 51% volume loss after 180 days. The EDS analysis did not detect any neodymium (Nd) in the mucosa or bone. The Mg-2 wt % Nd stents are a promising option when treating the narrow passages following paranasal sinus surgery. In particular, its good biocompatibility and good functionality facilitate the re-epithelization of these constricted passages. 2015 Wiley Periodicals, Inc.

Two well-known methods for enhancing the strength and controlling the anisotropy in magnesium alloys are precipitation hardening and grain size refinement. In this study, both methods are combined in an attempt to achieve optimal strengthening and anisotropy control: this was done via severe plastic deformation using Equal Channel Angular Processing (ECAP) of a precipitation hardenable magnesium alloy, Mg–6Zn–0.6Zr–0.4Ag–0.2Ca (wt%), within the temperature range of 125–200 °C. ECAP specimens were processed along different routes, where mechanically several of the ECAP samples show ultra-high strength levels approaching 400 MPa. The roles of grain size, texture, and precipitate morphology on mechanical properties are systematically investigated. It is shown here that the resulting microstructures generally show a refined grain size around 500 nm with a complex distribution of Mg-Zn enriched precipitates, which via ECAP either dynamically precipitate or are redistributed from the starting condition.

Neodymium containing magnesium alloys like MgNd2 and ZNdK100 offer high corrosion resistance and biocompatibility due to low amounts of alloying elements, and are thus attractive for biomedical applications. Compared with common bioresorbable magnesium alloys, which frequently contain mischmetal, the use of neodymium as a single rare earth element provides for good reproducibility of the degradation behavior while improving the ductility, leading to high fracture strains of 25–30%. Thus, stents made from these alloys allowed dilatation without failure. The MgNd2 alloy’s strength, however, turned out to be low. Recent investigations proved that the strength of a ZNdK100 alloy can be significantly increased by an adaptation of the extrusion parameters, such as billet temperature and extrusion ratio, which govern recrystallization of the microstructure. In the current study, it is demonstrated how the mechanical properties can be adjusted by the extrusion process, allowing the future use of the same alloy for both bone implants and soft tissue implants.

Magnesium as basic implant material has long been the center of orthopedic research. Latest progress is achieved with a European certification and clinical use of a magnesium based compression screw. However, long term studies with implantation duration that exceed one year considerably do not exist. The present examinations analyzed the degradation progress from nine months to 3.5 year after implantation of cylindrical pins into the medullary cavity of New Zealand White rabbits. Evaluation included clinical assessment, in vivo mu-computed tomography, analysis of the implants by three-point-bending and examination of the adjacent tissue by means of histology and of inner organs by mass- and optical emission spectrometry using inductively coupled plasma. Clinical acceptance was without objections in all animals. Immoderate reaction of the surrounding bone could be found in neither of the applied techniques. While in vivo is-computed tomography showed a very slow degradation rate up to 72 weeks, three-point-bending revealed a percentage loss of F(max) of 41.1% for implants after 9 months implantation and 88.47% for the implant after 3.5 years implantation. Although the total amounts of RE detected in the inner organs were very low, the organs of rabbits with LAE442 cylinders showed 10-20-fold increased concentrations of the alloying elements lanthanum, cerium, neodymium and praseodymium compared to animals without any implanted material.Statement of SignificanceThis is the first animal study investigating the degradation process of a magnesium alloy in vivo for up to 3.5 years. Currently available data from different other in vivo studies cover only implantation durations up to one year. Therefore, the analysis of these long-time effects in the present study is highly significant and of great interest. Comprehensive outcome achieved by different techniques was assessed. The degradation process was slow and homogenous. Maximum applied force (F(max)) reduced by 41.1% for implants after 9 months and by 88.47% for the implant after 3.5 years implantation. Total amounts of RE detected in the inner organs were very low; the organs of rabbits with LAE442 cylinders showed 10-20-fold increased concentrations. (C) 2016 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Magnesium alloys have promising mechanical and biological properties for the development of degradable implants. However, rapid implant corrosion and gas accumulations in tissue impede clinical applications. With time, the implant degradation rate is reduced by a highly biocompatible, phosphate-containing corrosion layer. To circumvent initial side effects after implantation it was attempted to develop a simple in vitro procedure to generate a similarly protective phosphate corrosion layer. To this end magnesium samples were pre-incubated in phosphate solutions. The resulting coating was well adherent during routine handling procedures. It completely suppressed the initial burst of corrosion and it reduced the average in vitro magnesium degradation rate over 56 days almost two-fold. In a small animal model phosphate coatings on magnesium implants were highly biocompatible and abrogated the appearance of gas cavities in the tissue. After implantation, the phosphate coating was replaced by a layer with an elemental composition that was highly similar to the corrosion layer that had formed on plain magnesium implants. The data demonstrate that a simple pre-treatment could improve clinically relevant properties of magnesium-based implants. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 1622-1635, 2017.

Biodegradable and biocompatible magnesium alloys appear to be very promising not only for temporary clinical application but also for developing deformable and degradable medical implants. This study analyzes the in vivo degradation behavior and the impact on the paranasal sinuses of the highly ductile Mg-2 wt%Nd alloy (MgNd2) in order to provide a basis for a satisfying stent system for the therapy of a chronic sinusitis. Moreover, in vitro tests were carried out on primary porcine nasal epithelial cells (PNEC). For the in vivo tests, cylindrical MgNd2 specimens were implanted into the sinus’ mucosa of minipigs. During and after a total period of 180 days the long-term biodegradation and biocompatibility properties after direct contact with the physiological tissue were analyzed. Biodegradation was investigated by measuring the mass and volume losses of the MgNd2 specimens as well as by performing element analyses to obtain information about the degradation layer. The influence on the surrounding tissue of paranasal sinuses was evaluated by endoscopic and histopathological examinations of the mucosa. Here, only a locally unspecific chronic infection was found. The degradation rate showed a maximum after 45 days postsurgery and was determined to decrease subsequently. In vitro experiments using PNEC showed adequate biocompatibility of MgNd2. This study demonstrates a good in vivo biocompatibility for MgNd2 in the system of paranasal sinuses and underlines the promising properties of alloy MgNd2 for biodegradable nasal stent applications.

Implants made of degradable magnesium alloys are a potential alternative to conventional orthopaedic implant materials, e.g. stainless steel or titanium. Intramedullary nails made of the magnesium alloy LAE442 were subjected to cyclic fatigue tests in both distilled water and Hank's Balanced Salt Solution (HBSS) at 37.5 °C until implant failure or a limit of 500,000 cycles was reached. In distilled water, four of the five nails were still intact after the end of the biomechanical test. In HBSS, a breakage within the first 70,000 bending cycles was observed. Additionally, the degradation rate of this alloy was determined in HBSS according to the weight loss method (0.24 ± 0.12 mm year−1) and based on gas release (0.21 ± 0.03 mm year−1) with a standard eudiometer. A cytotoxicity test with L929 cells was carried out in accordance with EN ISO 10993-5/12. This test demonstrated sufficient cell viability of the diluted extracts (50%, 25% and 12.5%). The relative metabolic activity of the 100% extract was reduced slightly below 70%, which is classified as a threshold value for cytotoxicity. In conclusion, this in vitro study indicates that intramedullary nails made of LAE442 may not have the required fatigue resistance for load-bearing applications and the development of a corrosion-protective coating may be necessary to prevent early failure of the implant.

The magnesium-neodymium alloy MgNd2 offers an elongation of 30%. Therefore, it is well suited as a material for resorbable stems which can be used for treating chronic sinusitis. While the alloy's corrosion properties were already investigated in vitro, the present study focuses on the in vivo degradation behavior of fluoride-coated and uncoated specimens in direct contact with porcine nasal mucosa during a period of 180 days. The study showed a promising and controlled biodegradation, which was investigated by measurements of the MgNd2 specimens' mass and volume losses as well as element analyses on the surface to obtain information about the composition of the degradation layer. The degradation rates of the uncoated samples in direct contact with the physiological tissue showed a maximum during the first 45 days which then decreased for the remaining implantation period. In contrast, the degradation rates of the fluoride-coated samples increased gradually during the implantation duration.

For the evaluation of new magnesium-based alloys, many different in vitro and in vivo methods are used. It was the aim of the current study to perform in vitro and in vivo corrosion studies of the new alloy Mg–La–Nd–Zr for its evaluation as a promising new degradable material and to compare commonly used evaluation methods. Die casted and subsequent extruded cylindrical pins (Ø1.5 mm; length 7 mm, n=18 ?>) were implanted subcutaneously (n= 6 ?>), intramuscular (n= 6 ?>) and intramedullary (n= 6 ?>) in female Lewis rats with a postoperative follow up of 8 weeks; subsequent μ-computed tomographical analyses (XTremeCT and μCT80) were performed as well as weight analysis prior to and after implantation. Cubes (5 mm  ×  4 mm  ×  4 mm; surface area, 1.12 cm2; n=44 ?>) were used for in vitro corrosion (HBSS and RPMI 1640 + 10% FBS medium) and cytocompatibility studies (L929 cells). First of all it could be stated that implant location strongly influences the in vivo corrosion rate. In particular, intramedullary implanted pins corroded faster than pins in a subcutaneous or intramuscular environment. Considering the different evaluation methods, the calculated ex vivo μCT-based corrosion rates resulted in comparable values to the corrosion rates calculated by the weight loss method, especially after chromatic acid treatment of the explanted pins. The in vitro methods used tend to show similar corrosion rates compared to in vivo corrosion, especially when a RPMI medium was used, and therefore are suitable to predict corrosion trends prior to in vivo studies. Regarding cytocompatibility, the novel magnesium alloy Mg–La–Nd–Zr showed sufficient cell viability and therefore can be considered as a promising alloy for further applications.

Up to now, different surgical techniques and stent systems have already been developed and tested for the continuous and adequate ventilation of the frontal sinuses. However, the results achieved still remain poor. Magnesium-based implants have been successfully used in numerous clinical applications. Offering excellent biocompatibility and biodegradability it may be the ideal material for the development of novel implants of the nasal sinus. Here, we present for the first time results on the behaviour of magnesium alloy in a unique environment, i.e. in contact to the nasal mucosa, air and nasal secretion. In a prospective longitudinal study, magnesium fluoride-coated MgNd2 specimens were implanted in the frontal sinuses of 12 minipigs for the investigation of biocompatibility and of the interface between the implant and the mucosa. Endoscopic examinations, histopathological evaluation and EDX measurements were performed regularly up to 180days. Endoscopic evaluation showed focal mucosal reaction, however, without affecting the patency of the sinus. In addition, no signs of bacterial infections were observed. The EDX analyses showed a marginal but steady increase in the Mg concentration in the mucosa over 180days. Histological analysis revealed a locally confined moderate mucosal hyperplasia and unspecific inflammatory reaction. Furthermore, we did not find any osteoinductive effects of the magnesium alloy. The results indicate the excellent biocompatibility of the MgNd2 alloy in contact with nasal mucosa and provide a novel material compound and solid proof-of-principle for the development of magnesium-based nasal stents.

Magnesium alloys are presently investigated as potential medical implant materials for temporary applications. Magnesium has been reported to have antibacterial activities and could therefore be used to prevent antibiotic treatment-resistant bacterial implant infections. For characterizing the effects of magnesium on infectious bacteria, bioluminescent S. aureus or P. aeruginosa were employed. The proliferation of both types of bacteria was suppressed in the presence of metallic magnesium and also in aqueous magnesium corrosion extracts. Of the two soluble corrosion products, magnesium ions were well tolerated while antibacterial activities correlated with increased pH levels of the supernatants. The alkaline pH alone was sufficient for the antibacterial effects which were completely abolished when the pH of the corrosion supernatants was neutralized. These results demonstrate that pH increases are necessary and sufficient for the antibacterial activity of metallic magnesium. In an animal model magnesium implants showed an enhanced but variable resistance to bacterial colonization.

Magnesium alloys are recommended as a potential material for osteosynthesis. It is known that storage-induced property modifications can occur in materials like aluminum. Thus the aim of this study was to analyze the influence of storage durations of up to 48 weeks on the biomechanical, structural, and degradation properties of the degradable magnesium alloy LAE442.

The frontal sinus recess consists of anatomically narrow passages that are prone to stenosis in endonasal frontal sinus surgery for chronic sinus disease. Over the past 100 years, diverse frontal sinus stents have been developed and evaluated in clinical and animal studies. However, superinfection, formation of granulations tissue, stent dislocation and late stenosis of the duct have remained challenges and subject of debate in the literature. Currently developed biodegradable materials, including rare earth-containing magnesium alloys are promising candidates for application as temporary implant materials. The Mg 2 % wt Nd alloy (MgNd2) was used to design a nasal stent that fit the porcine anatomy. In the current study, we evaluate biocompatibility, biodegradation and functionality of a frontal sinus stent in 16 minipigs over 6 months. Intraoperative endoscopy revealed free stent lumen in all cases. Blood examination and clinical examinations indicated no systematic or local inflammation signs. The histopathology and elements analysis showed a very good biocompatibility. The μ-computed tomography-based volumetric analysis showed substantial stent degradation within 6 months. Our MgNd2 based stent appears to be a promising, solid basis for the development of a frontal sinus stent for clinical use.

Coating Systems for Biodegradable Magnesium Applications Jan-Marten Seitz, Jan-Marten Seitz Institut für Werkstoffkunde (IW), Leibniz Universität Hannover, An der Universität 2, 30823 Hannover, GermanySearch for more papers by this authorRainer Eifler, Rainer Eifler Institut für Werkstoffkunde (IW), Leibniz Universität Hannover, An der Universität 2, 30823 Hannover, GermanySearch for more papers by this authorMatthew Vaughan, Matthew Vaughan Department of Mechanical Engineering, Texas A&M University, College Station, TX 77843-3123, USASearch for more papers by this authorChris Seal, Chris Seal Department of Chemical and Materials Engineering, The University of Auckland, Private Bag 92019, Auckland, New ZealandSearch for more papers by this authorMargaret Hyland, Margaret Hyland Light Metals Research Centre, The University of Auckland, Private Bag 92019, Auckland, New ZealandSearch for more papers by this authorHans Jürgen Maier, Hans Jürgen Maier Institut für Werkstoffkunde (IW), Leibniz Universität Hannover, An der Universität 2, 30823 Hannover, GermanySearch for more papers by this author Jan-Marten Seitz, Jan-Marten Seitz Institut für Werkstoffkunde (IW), Leibniz Universität Hannover, An der Universität 2, 30823 Hannover, GermanySearch for more papers by this authorRainer Eifler, Rainer Eifler Institut für Werkstoffkunde (IW), Leibniz Universität Hannover, An der Universität 2, 30823 Hannover, GermanySearch for more papers by this authorMatthew Vaughan, Matthew Vaughan Department of Mechanical Engineering, Texas A&M University, College Station, TX 77843-3123, USASearch for more papers by this authorChris Seal, Chris Seal Department of Chemical and Materials Engineering, The University of Auckland, Private Bag 92019, Auckland, New ZealandSearch for more papers by this authorMargaret Hyland, Margaret Hyland Light Metals Research Centre, The University of Auckland, Private Bag 92019, Auckland, New ZealandSearch for more papers by this authorHans Jürgen Maier, Hans Jürgen Maier Institut für Werkstoffkunde (IW), Leibniz Universität Hannover, An der Universität 2, 30823 Hannover, GermanySearch for more papers by this author Book Editor(s):Martyn Alderman, Martyn AldermanSearch for more papers by this authorMichele V. Manuel, Michele V. ManuelSearch for more papers by this authorNorbert Hort, Norbert HortSearch for more papers by this authorNeale R. Neelameggham, Neale R. NeelamegghamSearch for more papers by this author First published: 01 February 2014 https://doi.org/10.1002/9781118888179.ch70Citations: 1 AboutPDFPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShareShare a linkShare onFacebookTwitterLinked InRedditWechat Summary This chapter contains sections titled: Introduction Materials and Methods Results and Discussion Conclusions Acknowledgements Citing Literature Magnesium Technology 2014 RelatedInformation

Using several different in vitro assays, a new biodegradable magnesium alloy Mg–2La, composed of 98% magnesium and 2% lanthanum, was investigated as a possible implant material for biomedical applications. An in vitro cytotoxicity test, according to EN ISO 10993-5/12, with L929 and human osteoblastic cells identified no toxic effects on cell viability at physiological concentrations (at 50% dilutions and higher). The metabolic activity of human osteoblasts in the 100% extract was decreased to <70% and was therefore rated as cytotoxic. The degradation rates of Mg–2La were evaluated in phosphate buffered saline and four different cell culture media. The degradation rates were shown to be influenced by the composition of the solution, and the addition of fetal bovine serum slightly accelerated the corrosive process. The results of these in vitro experiments suggest that Mg–2La is a promising candidate for use as an orthopedic implant material.