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The corrosion performances of the as-cast and solution-treated Mg-0.5Zn samples were investigated in 0.9% NaCl solution and compared. From the electrochemical measurement results and corrosion morphology observations, it is found that the corrosion resistance of Mg-0.5Zn deteriorated with the extension of solution treatment duration. The main reason was the formation of Fe-Si precipitates with higher Fe concentrations during heat treatment. The Fe-Si precipitates, especially the ones with high Fe contents influenced the corrosion initiation and propagation significantly. In regard of corrosion performance, the solution-treated and then extruded sample was also performing not as good as the cast and then directly extruded sample.

To understand the magnesium (Mg) degradation mechanism in vivo, a variety of in vitro investigations have been conducted. However, there is still a gap between in vitro results and in vivo observations. Herein, the combined effect of proteins and medium-flow conditions on magnesium degradation was studied. Bovine serum albumin (BSA) and fetal bovine serum (FBS) were employed as the commonly used protein components for in vitro tests. Static, medium-changing (semi-static) and continuous-medium-flow (dynamic) conditions were used as different conditions. The results showed the highest inhibition efficiency of BSA and FBS on magnesium degradation under static conditions, while the efficiency largely decreased under semi-static or dynamic conditions, particularly for BSA. The possible explanations are related to the composition of degradation products and the integrity of the degradation layer. These results emphasize the importance of considering effects from different factors during magnesium degradation.

Degradability of bone tissue engineering scaffold that matching the regeneration rate could allow a complete replacement of host tissue. However, the porous structure of biodegradable Mg scaffolds certainly generated high specific surface area, and the three-dimensional interconnected pores provided fast pervasive invasion entrance for the corrosive medium, rising concern of the structural integrity during the degradation. To clarify the structural evolution of the three-dimensional (3D) porous structure, semi-static immersion tests were carried out to evaluate the degradation performance in our previous study. Nevertheless, dynamic immersion tests mimicking the in vivo circulatory fluid through the interconnected porous structure have yet been investigated. Moreover, the effects of dynamic flow rates on the degradation deposition behavior of 3D porous Mg scaffolds were rarely reported. In this study, Mg scaffolds degraded at three flow rates exhibited different degradation rates and deposition process. A flow rate of 0.5 mL/min introduced maximum drop of porosity by accumulated deposition products. The deposition products provided limited protection against the degradation process at a flow rate of 1.0 mL/min. The three-dimensional interconnected porous structure of Mg scaffold degraded at 2.0 mL/min well retained after 14 days showing the best interconnectivity resistance to the degradation deposition process. The dynamic immersion tests disclosed the reason for the different degradation rates on account of flow rates, which may bring insight into understanding of varied in vivo degradation rates related to implantation sites.

Treatment of physeal fractures (15%–30% of all paediatric fractures) remains a challenge as in approximately 10% of the cases, significant growth disturbance may occur. Bioresorbable Magnesium-based implants represent a strategy to minimize damage (i.e., load support until bone healing without second surgery). Nevertheless, the absence of harmful effects of magnesium-implants and their degradation products on the growth plate should be confirmed. Here, the proteome of human mesenchymal stem cells undergoing chondrogenesis was evaluated when exposed to the products of various Magnesium-based materials degradation. The results of this study indicate that the materials induced regulation of proteins associated with cell chondrogenesis and cartilage formation, which should be beneficial for cartilage regeneration., Graphical abstract Image 1, Highlights • Degradation products from Mg-based materials generated changes in protein expression. • Relevant proteins involved in cartilage formation were upregulated. • Potential application of especially Pure-Mg and Mg-10Gd for cartilage regeneration.

Bovine serum albumin (BSA) or fetal bovine serum (FBS), as the protein component, is usually added into solution to study the influence of proteins on Mg degradation. However, the specific character of proteins used and the interaction between organic molecules in FBS do not draw enough attention. This study investigated the influence of BSA, fibrinogen (Fib) and FBS on Mg degradation in Hanks’ balanced salt solution without (HBSS) or with calcium (HBSSCa) and Dulbecco's modified eagle medium Glutamax-I (DMEM). The results reveal that the effect of BSA, Fib and FBS on the degradation rate of Mg is time- and media-dependent, as a result of the overlap of protein adsorption, binding/chelating to ions and interaction between organic molecules. The binding/chelating of proteins and/or the possible effect of proteins on the kinetics of products formation lead to the formation of different degradation precipitates on Mg surface in HBSS. The interaction between proteins and Ca2+/PO43− accelerates the formation of Ca-P salts in HBSSCa and DMEM, thereby impeding the degradation of Mg. Moreover, the interplay between organic molecules and the specific character of proteins are highlighted by the cooperative (in media + FBS) or competitive (in DMEM + BSA + Fib) effect of proteins in the presence of more kinds of proteins and the different effect of BSA and Fib on the degradation of Mg. Therefore, the addition of proteins to testing medium is necessary for in vitro tests and DMEM + 10% FBS is recommended as the in vitro testing medium to present an in vivo-like degradation for Mg. Statement of significance The present study emphasizes the difference between proteins, and the difference between single protein and protein mixture in view of the effect on Mg degradation. The results highlight the importance of the interaction between proteins in media, which can increase or decrease the degradation of Mg compared to the single protein. It can aid other researchers to understand the effect of proteins on Mg degradation and to pay more attention to the interaction of organic molecules on Mg degradation when more kinds of organic molecules are used in medium, especially for FBS. The submitted work could be of significant importance to other researchers working in the related fields, thus appealing to the readers of Acta Biomaterialia.

The application of Mg–Ag alloys is suggested as biodegradable implant materials in the form of sheets with controllable mechanical properties and appropriate degradation behavior. This study aimed on the understanding of influence of rolling temperature and silver content (2–8 wt %) on the microstructure development, mechanical properties and the degradation behavior of the sheet material. Besides an increase of the average grain size with increasing rolling temperature, precipitates of Mg54Ag17 formed during processing at lower temperatures and resulted in grain growth restriction during recrystallization. A typical alignment of basal planes parallel to the sheet plane was confirmed by texture measurements along with a strengthening of such textures when grains grew larger during recrystallization. As a result, an increase of the Ag-content corresponds to an increase in the hardness and strength properties of the sheets. In immersion tests, the as-rolled and annealed Q6 and Q8 rolled at 400 °C or 450 °C had similar degradation rate but an obvious difference of the degradation morphology due to the existence of precipitates at grain boundaries. By elevating the rolling and annealing temperature, the degradation rate decreased and the elimination of precipitates led to homogeneous degradation even when the silver in magnesium was up to 8 wt%. Appropriate short time annealing procedures below 60 s allow the tailored regulation of hardness, mechanical properties and ductility via controlled static recrystallization.

Simulated body fluid (SBF) is a common medium for in vitro corrosion analysis. The individual influence and synergy of the SBF components on the corrosion of commercially pure Mg are investigated in this study. The results demonstrate that corrosion acceleration in presence of the synthetic pH buffer, Tris/HCl, is attributed to the combined effect of three factors: increased Cl− concentration, complexation of Mg2+ and Ca2+ and consumption of OH− needed for products formation. In Tris/HCl-free SBF, the synergy between Ca2+, Mg2+, HPO42- and HCO3− assures slowest Mg degradation due to growth of partially protective layer that becomes thicker with time.

Although certified magnesium-based implants are launched some years ago, the not well-defined Mg degradation mechanism under physiological conditions makes it difficult to standardize its use as a degradable biomaterial for a wide range of implant applications. Among other variables influencing the Mg degradation mechanism, monitoring the pH in the corrosive solution and, especially, at the corroding interface is important due to its direct relation with the formation and stability of the degradation products layer. The interface pH (pH at the Mg/solution interface) developed on Mg-2Ag and E11 alloys are studied in situ during immersion under dynamic conditions (1.5 mL min-1 ) in HBSS with and without the physiological amount of Ca2+ cations (2.5 × 10-3 m). The results show that the precipitation/dissolution of amorphous phosphate-containing phases, that can be associated with apatitic calcium-phosphates Ca10- x (PO4 )6- x (HPO4 or CO3 )x (OH or ½ CO3 )2- x with 0 ≤ x ≤ 2 (Ap-CaP), promoted in the presence of Ca2+ generates an effective local pH buffering system at the surface. Thus, high alkalinization is prevented, and the interface pH is stabilized in the range of 7.6 to 8.5.

Several material parameters affect degradation characteristics of Mg and its alloys under physiological conditions. Porous Mg materials are interesting for their simultaneous degradation and drug delivery capabilities. However, an increase in pore surface area is detrimental to both degradation resistance and subsequent mechanical properties. The present work aims at determining the threshold porosity value in Mg–0.6Ca specimens produced by powder metallurgy (PM) below which low degradation rates persist with acceptable mechanical properties. Seven different porous Mg–0.6Ca specimens containing both closed and open pore structures were fabricated with porosities ranging from 3% to 21%. Degradation profiles were obtained via a semi static immersion test over 16 days under physiological conditions using Dulbecco\'s modified Eagle\'s medium with Glutamax and 10% fetal bovine serum as supplements. The results are related to morphological pore parameters like pore size distribution, pore interconnectivity and pore curvatures that were quantified using an ex situ µCT analysis. In general, with decreasing porosity a decrease in pore interconnectivity is seen followed by rounding of the pores. Low degradation rates (MDR < 0.3 mm/year) are observed in specimens until 10% porosity, however, the upper bound for reproducible degradation is observed to be in specimens until 12% porosity. This porosity level also marks the transition from closed to open pore nature with a simultaneous change in pore interconnectivity from less than 10% to greater than 95%, below and above this porosity level, respectively. The tensile strength and elongation to failure recorded for specimens with 10% porosity were 70 MPa and 2%, respectively displaying positive traits of both homogenous degradation and mechanical properties. The results suggest that high pore interconnectivity is the dominant factor controlling degradation and mechanical properties in porous Mg-0.6Ca specimens. The results also indicate a good sintering response of Mg-0.6Ca specimens providing further material development towards biomaterial applications.

The interaction between organic molecules and biomaterial surfaces determines the fate of biomaterials during their service life, which is also the research hotspots in the field of biomaterials. To understand the mechanism of protein interaction with magnesium (Mg) degradation, alloying elements, immersion time, protein concentration and surface conditions have been previously considered for the effect of proteins on Mg degradation. However, fluid flow, as one of the critical factors, drew little attention in this case. In the present study, the effect of bovine serum albumin (BSA) and fetal bovine serum (FBS) on Mg degradation was compared under static and dynamic conditions. The results revealed that both BSA and FBS slightly decreased the degradation rate of Mg in Hanks’ balanced salt solution (HBSS) under static immersion due to the protein adsorption and the formation of a Ca/P-rich top layer on Mg surface, whereas under dynamic flow condition the degradation of Mg was significantly accelerated in the presence of BSA or FBS. The reasons seemed to stem from the weakened protein adsorption on Mg surface in this case and the dynamically enhanced interaction between proteins and ions/products in solutions, which largely weaken the combination of the top Ca/P-rich layer with the inner corrosion product layer. These results highlight the importance of testing conditions for Mg characterization in vitro and the synergistic effect between different parameters on Mg degradation.

Acta biomaterialia 121, 695 - 712 (2021). doi:10.1016/j.actbio.2020.11.050, The influence of amount of intermetallics on the degradation of as-extruded Mg-Nd alloys with different contents of Nd was investigated via immersion testing in DMEM+10% FBS under cell culture conditions and subsequent microstructural characterizations. It is found that the presence of intermetallic particles Mg$_{41}$Nd$_5$ affects the corrosion of Mg-Nd alloys in two conflicting ways. One is their negative role that their existence enhances the micro-galvanic corrosion. Another is their positive role. Their existence favours the formation of a continuous and compact corrosion layer. At the early stage of immersion, their negative role predominated. The degradation rate of Mg-Nd alloys monotonously increases with increasing the amount of intermetallics. Mg-$_5$Nd alloy with maximum amount of intermetallics suffered from the most severe corrosion. With the immersion proceeding (≥7 days), then the positive role of these intermetallic particles Mg$_{41}$Nd$_5$ could not be neglected. Owing to the interaction between their positive and negative roles, at the later stage of immersion the corrosion rate of Mg-Nd alloys first increases with increasing the content of Nd, then reaches to the maximum at 2 wt. % Nd. With a further increase of Nd content, a decrease in corrosion rate occurs. The main corrosion products on the surfaces of Mg-Nd alloys include carbonates, calcium-phosphate, neodymium oxide and/or neodymium hydroxide. They are amorphous at the early stage of immersion. With the immersion proceeding, they are transformed to crystalline. The existence of undegradable Mg$_{41}$Nd$_5$ particles in the corrosion layer can enhance the crystallization of such amorphous corrosion products., Published by Elsevier, [Amsterdam]

The influence of intermetallic microstructure on the degradation of Mg-5Nd alloy with different heat treatments was investigated via immersion testing in DMEM + 10 pct FBS under cell culture conditions and subsequent microstructural characterizations. It was found that T4 heat-treated sample had the poorest corrosion resistance due to the lack of finely dispersed precipitates inside grains, continuous lamellar particles along grain boundaries and outer Ca-P layer, and to the formation of a loose corrosion product layer. In contrast, the aged samples exhibited a better corrosion resistance due to their presence and to the formation of a compact corrosion layer. Their degradation behavior largely depended on the intermetallic microstructure. Corrosion was initiated in the matrix around stable globular particles Mg41Nd5 at grain boundaries. In the sample aged at high temperature 245 °C, the coexistence of lamellar Mg41Nd5 particles and their nearby Nd-poor regions enhanced the corrosion. The corrosion first started in such regions. It was shown that those finely dispersed precipitates formed during aging had no influence on the corrosion initiation. However, they indeed affected the subsequent corrosion propagation with the immersion proceeding. They supplied barriers for corrosion propagation and hence were beneficial for improving the corrosion resistance. The continuously distributed lamellar Mg41Nd5 precipitates formed at grain boundaries during aging at 245 °C supplied an additional effective obstacle to corrosion propagation. This was especially beneficial for hindering the corrosion propagation at the later stage of corrosion.

Although the adsorption of proteins on the Mg surface was ascribed to be the main reason for the effect of proteins on magnesium (Mg) degradation, few studies about the adsorption of proteins on the Mg surface were performed due to the labile circumstances during immersion. In the present study, the adsorption of bovine serum albumin (BSA) and fibrinogen (Fib) on the Mg surface during and after immersion was extensively investigated in different media for the first time. The results revealed that BSA and Fib showed a similar adsorption trend on the Mg surface during and after immersion, and they adsorbed more on the Mg surface in Hank’s balanced salt solution (HBSS) than in Dulbecco’s modified Eagle medium Glutamax-I (DMEM). The possible influence factors for protein adsorption, such as pH, surface roughness, and wettability, were considered to elucidate different adsorption in HBSS and DMEM. It was found that the participation of Ca2+ in the formation of degradation products largely affected the degradat...

The degradation behavior in consideration of the pore strut and the interconnectivity of two Mg scaffolds with different three-dimensional interconnected porous structures were evaluated. The interconnectivity of the two scaffolds gradually decreased along with the clogged interconnected pores due to the deposition formation on the pore wall. Mg scaffold with spherical pores and cambered pore strut degraded faster but exhibited better resistance to the deterioration of the interconnectivity compared with Mg scaffold with irregular pores and polygonal pore struts. Direct cell culture of MC3T3-E1 osteoblasts on the two scaffolds indicated a promising potential for bone tissue engineering.

High-resolution analytical methods, including synchrotron infrared microspectroscopy combined with wavelength-dispersive X-ray emission spectroscopy were applied to study the structure and chemical composition of the oxidized layer of pure and Ag-alloyed Mg exposed to cell culture media without and with osteoblasts. Comparative analysis has been done on pure Mg immersed in two different cell culture media: Dulbecco\'s Modified Eagle\'s Medium (DMEM) and Roswell Park Memorial Institute medium (RPMI), whereas Mg-xAg binary alloys (x = 2, 4, 6, 8 wt%) were studied after immersion in DMEM. It is shown that the physicochemical formation of degradation products as well as the activity of the biological component is influenced by the addition of silver. It could be demonstrated that the presence of Ag in the Mg alloy enhances the chemical reaction between Mg and C to form amorphous and/or crystalline MgCO3 on account of CaCO3. As a consequence, the further available P and Ca react easily to form Mg-poor amorphous calcium phosphate phases. Osteoblasts actively adjusted these phases towards hydroxyapatite-like phases.

This review focusses on the application of physiological conditions for the mechanistic understanding of magnesium degradation. Despite the undisputed relevance of simplified laboratory setups for alloy screening purposes, realistic and predictive in vitro setups are needed. Due to the complexity of these systems, the review gives an overview about technical measures, defines some caveats and can be used as a guideline for the establishment of harmonized laboratory approaches., Graphical abstract Image 1, Highlights • Physiological conditions are mandatory for mechanistic understanding of magnesium degradation. • Guidelines and caveats for experimental setups are reviewed. • Media composition is essential for reliable experiments.

Several typical organic components, l -ascorbic acid ( l -AA), l -glutamine ( l -Gln), l -alanyl- l -glutamine ( l -Ala- l -Gln) and fetal bovine serum (FBS) were chosen to elucidate the effects of organic components on the degradation of pure Mg under cell culture conditions. The results revealed that the influence of organic components on the degradation of pure Mg is time-dependent and they play an important role in the formation of the degradation layer. The addition of organic components favors the precipitation of nesquehonite rather than hydromagnesite in the “outer” layer, while in the “inner” layer the organic components accelerates the formation of phosphate (Mg-PO4, Ca-P salts) during immersion.

Magnesium and its alloys have in recent years emerged as a promising alternative to titanium-based implants for medical applications due to favorable degradation properties and good biocompatibility. The degradation of materials is currently investigated by studying different samples of the same material at different time points after degradation in a medium. This study is presenting a high-resolution time-lapse investigation of Mg-2Ag in culture medium using synchrotron radiation-based micro-computed tomography over the course of 5 days. The design of the custom-built corrosion cell and bioreactor are described. The computed degradation rate after 5 days is in agreement with the literature. SRµCT enables the segmentation of cracks forming in the degradation layer due to stresses and hydrogen development.

Summary To better understand the association between high salt intake and osteoporosis, we investigated the effect of sodium chloride (NaCl) on mice and human osteoclastogenesis. The results suggest a direct, activating role of NaCl supplementation on bone resorption. Introduction High NaCl intake is associated with increased urinary calcium elimination and parathyroid hormone (PTH) secretion which in turn stimulates the release of calcium from the bone, resulting in increased bone resorption. However, while calciuria after NaCl loading could be shown repeatedly, several studies failed to reveal a significant increase in PTH in response to a high-sodium diet. Another possible explanation that we investigated here could be a direct effect of high-sodium concentration on bone resorption. Methods Mouse bone marrow macrophage and human peripheral blood mononuclear cells (PBMC) driven towards an osteoclastogenesis pathway were cultivated under culture conditions mimicking hypernatremia environments. Results In this study, a direct effect of increased NaCl concentrations on mouse osteoclast differentiation and function was observed. Surprisingly, in a human osteoclast culture system, significant increases in the number of tartrate-resistant acid phosphatase (TRAP)-positive osteoclasts, calcitonin receptor (CTR)-positive osteoclasts, nuclear factor-activated T cells c1 (NFATc1) gene expression, and areal and volumetric resorptions were observed for increasing concentrations of NaCl. This suggests a direct, activating, cell-mediated effect of increased concentrations of NaCl on osteoclasts. Conclusions The reported that enhanced bone resorption after high-sodium diets may not only be secondary to the urinary calcium loss but may also be a direct, cell-mediated effect on osteoclastic resorption. These findings allow us to suggest an explanation for the clinical findings independent of a PTH-mediated regulation.

The present work applies the law of mass conservation toward an analytical model describing the long-term degradation of Mg-0.3Ca implant material in defined physiological electrolyte environments. The model takes into account surface conversion and degradation product deposition related changes of degradation rates by introducing an effective layer thickness. The analytical nature of the approach does not consider detailed chemical and electrochemical process. Thus, it simply declares an effective damping term. In this way it can be applied easily for the prediction of materials failure in the named environments. Restrictions of the approach will be discussed as well since validity relates to a number of aspects.

The present work reports on PEO coatings which can be potentially used for degradation control of Mg-based implant materials. Three coatings were developed on Mg-0.8wt%Ca alloy: two in an electrolyte with fluoride species using different treatment times and one in a fluoride-free electrolyte. Uncoated and coated materials were examined in terms of structure and morphology using TEM, SEM and XRD. The corrosion investigations on fluoride-containing samples were performed using DC potentiodynamic curves, EIS and hydrogen evolution measurements. Both PEO coatings improved the corrosion resistance compared to the bulk material and the best behaviour was found for the thinnest PEO coating (PEO1-F). The amount of released F− ions was also measured with the aim of underpinning the effect of coatings and presence of fluorides species on the cell response. The bulk material and the coated alloy were studied using live/dead cell test, with the best results obtained for thinner fluoride containing coatings.

The purpose of this study was to compare short term in vitro and in vivo biodegradation studies with low purity Mg (> 99.94 %), Mg-10Gd and Mg-2Ag designed for biodegradable implant applications. Three in vitro testing conditions were applied, using (i) phosphate buffered saline (PBS), (ii) Hank's balanced salt solution (HBSS) and (iii) Dulbecco's modified eagle medium (DMEM) in 5 % CO2 under sterile conditions. Gas evolution and mass loss (ML) were assessed, as well as the degradation layer, by elemental mapping and scanning electron microscopy (SEM). In vivo, implantations were performed on male Sprague-Dawley rats evaluating both, gas cavity volume and implant volume reduction by micro-computed tomography (µCT), 7 d after implantation. Samples were produced by casting, solution heat treatment and extrusion in disc and pin shape for the in vitro and in vivo experiments, respectively. Results showed that when the processing of the Mg sample varied, differences were found not only in the alloy impurity content and the grain size, but also in the corrosion behaviour. An increase of Fe and Ni or a large grain size seemed to play a major role in the degradation process, while the influence of alloying elements, such as Gd and Ag, played a secondary role. Results also indicated that cell culture conditions induced degradation rates and degradation layer elemental composition comparable to in vivo conditions. These in vitro and in vivo degradation layers consisted of Mg hydroxide, Mg-Ca carbonate and Ca phosphate. ispartof: EUROPEAN CELLS & MATERIALS vol:33 pages:90-104 ispartof: location:Switzerland status: published

Metallic implant biomaterials predominate in orthopaedic surgery. Compared to titanium-based permanent implants, magnesium-based ones offer new possibilities as they possess mechanical properties closer to the ones of bones and they are biodegradable. Furthermore, magnesium is more and more considered to be “bioactive” i.e., able to elicit a specific tissue response or to strengthen the intimate contact between the implant and the osseous tissue. Indeed, several studies demonstrated the overall beneficial effect of magnesium-based materials on bone tissue (in vivo and in vitro). Here, the direct effects of titanium and magnesium on osteoblasts were measured on proteomes levels in order to highlight metal-specific and relevant proteins. Out of 2100 identified proteins, only 10 and 81 differentially regulated proteins, compare to the control, were isolated for titanium and magnesium samples, respectively. Selected ones according to their relationship to bone tissue were further discussed. Most of them were involved in extracellular matrix maturation and remodelling (two having a negative effect on mineralisation). A fine-tuned balanced between osteoblast maturation, differentiation and viability was observed.

The degradation rate of magnesium (Mg) alloys is a key parameter to develop Mg-based biomaterials and ensure in vivo-mechanical stability as well as to minimize hydrogen gas production, which otherwise can lead to adverse effects in clinical applications. However, in vitro and in vivo results of the same material often differ largely. In the present study, a dynamic test bench with several single bioreactor cells was constructed to measure the volume of hydrogen gas which evolves during magnesium degradation to indicate the degradation rate in vivo. Degradation medium comparable with human blood plasma was used to simulate body fluids. The media was pumped through the different bioreactor cells under a constant flow rate and 37 &deg, C to simulate physiological conditions. A total of three different Mg groups were successively tested: Mg WE43, and two different WE43 plasma electrolytically oxidized (PEO) variants. The results were compared with other methods to detect magnesium degradation (pH, potentiodynamic polarization (PDP), cytocompatibility, SEM (scanning electron microscopy)). The non-ceramized specimens showed the highest degradation rates and vast standard deviations. In contrast, the two PEO samples demonstrated reduced degradation rates with diminished standard deviation. The pH values showed above-average constant levels between 7.4&ndash, 7.7, likely due to the constant exchange of the fluids. SEM revealed severe cracks on the surface of WE43 after degradation, whereas the ceramized surfaces showed significantly decreased signs of corrosion. PDP results confirmed the improved corrosion resistance of both PEO samples. While WE43 showed slight toxicity in vitro, satisfactory cytocompatibility was achieved for the PEO test samples. In summary, the dynamic test bench constructed in this study enables reliable and simple measurement of Mg degradation to simulate the in vivo environment. Furthermore, PEO treatment of magnesium is a promising method to adjust magnesium degradation.

Considering the excellent biocompatibility of magnesium (Mg) alloys and their better mechanical properties compared to polymer materials, a wrought MgZnCa alloy with low contents of Zn (0.7 wt%) and Ca (0.6 wt%) (ZX11) was developed by twin roll casting (TRC) technology as potential biodegradable bone plates. The degradability and cell response of the ZX11 alloy were evaluated in vitro, as well as the mechanical integrity according to tensile tests after immersion. The results revealed a slightly higher degradation rate for the rolled ZX11, in comparison to that of the annealed one. It was mainly caused by the deformation twins and residual strain stored in the rolled alloy, which also seemed to promote localized degradation, thereby leading to a relatively fast deterioration in mechanical properties, especially the fracture strain/elongation. In contrast, after the annealing treatment, the alloy showed relatively lower strength, yet a lower degradation rate and quite stable elongation during the initial weeks of immersion were observed. More importantly, the ZX11 alloy, regardless of the annealing treatment, showed good in vitro cytocomopatibility regarding human primary osteoblasts. The assessment indicates the rolled alloy as a good choice for implantation sites where relatively high mechanical strength is needed during the early implantation, while the annealed alloy is a potential candidate for the sites which demand stable mechanical integrity during service. Statement of Significance The development of magnesium alloys as bone implants demands low degradation rate to gain not only a slow hydrogen evolution, but also a stable mechanical integrity during service. The present study develops a micro-alloyed MgZnCa alloy via twin roll casting (TRC) technology. It exhibited limited cytotoxicity, fairly low degradation rate and comparable strength to the reported Mg-1Zn-5Ca alloy which has been used as bone screws in clinical trials, indicating the great potential application as biodegradable bone implants. Furthermore, it showed good mechanical integrity during immersion to support the defect healing. Our results can aid other researchers to evaluate the mechanical integrity of biodegradable materials and to pay more attention to the effect of degradation behaviour on mechanical integrity of materials.

This work studies the in vitro degradation of Mg alloys for bioabsorbable implant applications under near physiological conditions. For this purpose, the degradation behaviour of Mg alloys in Dulbecco's modified eagle medium (DMEM) which is a commonly used cell culture medium is analysed. Unfortunately, DMEM can be contaminated by microorganisms, acidifying the medium and accelerating the Mg degradation process by dissolution of protective degradation layers, such as (Mgx,Cay)(PO4)z. In this paper the influence of sterilization by applying UV-C radiation and antibiotics (penicillin/streptomycin) is analysed with two implant material candidates: Mg-Gd and Mg-Ag alloys; and pure magnesium as well as Mg-4Y-3RE as a reference.

The effects of micro-addition (0.2 wt.%) of Ca, Sr, Ag, In and Cu on the microstructure and corrosion properties of the as-cast Mg-0.5Zn alloy were systematically studied. It is found that the grain refinement efficiency and intermetallics forming ability differed greatly among these elements. Si impurity also played a vital role in the precipitates formation in all systems. It is generally observed that Mg-Zn-Ca possessed the highest corrosion resistance due to the refined grain size, limited intermetallics and uniform corrosion, whereas Mg-Zn-Cu showed the highest corrosion rate due to the coarse grains, intermetallics activity and severe pitting corrosion. With the exception of Mg-Zn-Cu, the corrosion performances of Mg-0.5Zn(-0.2X) alloys were comparable with the higher concentrated systems from literature, indicating the feasibility of these micro-alloying systems for biomedical applications.

Magnesium (Mg)-based biomaterials are promising candidates for bone and tissue regeneration. Alloying and surface modifications provide effective strategies for optimizing and tailoring their degradation kinetics. Nethertheless, biocompatibility analyses of Mg-based materials are challenging due to its special degradation mechanism with continous hydrogen release. In this context, the hydrogen release and the related (micro-) milieu conditions pretend to strictly follow in vitro standards based on ISO 10993-5/-12. Thus, special adaptions for the testing of Mg materials are necessary, which have been described in a previous study from our group. Based on these adaptions, further developments of a test procedure allowing rapid and effective in vitro cytocompatibility analyses of Mg-based materials based on ISO 10993-5/-12 are necessary. The following study introduces a new two-step test scheme for rapid and effective testing of Mg. Specimens with different surface characteristcis were produced by means of plasma electrolytic oxidation (PEO) using silicate-based and phosphate-based electrolytes. The test samples were evaluated for corrosion behavior, cytocompatibility and their mechanical and ostogenic properties. Thereby, two PEO ceramics could be identified for further in vivo evaluations.

Magnesium (Mg)-based biomaterials are promising candidates for bone and tissue regeneration. Alloying and surface modifications provide effective strategies for optimizing and tailoring their degradation kinetics. Nevertheless, biocompatibility analyses of Mg-based materials are challenging due to its special degradation mechanism with continuous hydrogen release. In this context, the hydrogen release and the related (micro-) milieu conditions pretend to strictly follow in vitro standards based on ISO 10993-5/-12. Thus, special adaptions for the testing of Mg materials are necessary, which have been described in a previous study from our group. Based on these adaptions, further developments of a test procedure allowing rapid and effective in vitro cytocompatibility analyses of Mg-based materials based on ISO 10993-5/-12 are necessary. The following study introduces a new two-step test scheme for rapid and effective testing of Mg. Specimens with different surface characteristics were produced by means of plasma electrolytic oxidation (PEO) using silicate-based and phosphate-based electrolytes. The test samples were evaluated for corrosion behavior, cytocompatibility and their mechanical and osteogenic properties. Thereby, two PEO ceramics could be identified for further in vivo evaluations., International journal of molecular sciences;Jg. 20, Heft 2. S. 255-1-255-20

Magnesium and its alloys have considerable potential for orthopedic applications. During the degradation process the interface between material and tissue is continuously changing. Moreover, too fast or uncontrolled degradation is detrimental for the outcome in vivo. Therefore in vitro setups utilizing physiological conditions are promising for the material/degradation analysis prior to animal experiments. The aim of this study is to elucidate the influence of inorganic salts contributing to the blood buffering capacity on degradation. Extruded pure magnesium samples were immersed under cell culture conditions for 3 and 10 days. Hank's balanced salt solution without calcium and magnesium (HBSS) plus 10% of fetal bovine serum (FBS) was used as the basic immersion medium. Additionally, different inorganic salts were added with respect to concentration in Dulbecco's modified Eagle's medium (DMEM, in vitro model) and human plasma (in vivo model) to form 12 different immersion media. Influences on the surrounding environment were observed by measuring pH and osmolality. The degradation interface was analyzed by electron-induced X-ray emission (EIXE) spectroscopy, including chemical-element mappings and electron microprobe analysis, as well as Fourier transform infrared reflection micro-spectroscopy (FTIR).

Magnesium-based implants exhibit several advantages, such as biodegradability and possible osteoinductive properties. Whether the degradation may induce cell type-specific changes in metabolism still remains unclear. To examine the osteoinductivity mechanisms, the reaction of bone-derived cells (MG63, U2OS, SaoS2, and primary human osteoblasts (OB)) to magnesium (Mg) was determined. Mg-based extracts were used to mimic more realistic Mg degradation conditions. Moreover, the influence of cells having direct contact with the degrading Mg metal was investigated. In exposure to extracts and in direct contact, the cells decreased pH and osmolality due to metabolic activity. Proliferating cells showed no significant reaction to extracts, whereas differentiating cells were negatively influenced. In contrast to extract exposure, where cell size increased, in direct contact to magnesium, cell size was stable or even decreased. The amount of focal adhesions decreased over time on all materials. Genes involved in bone formation were significantly upregulated, especially for primary human osteoblasts. Some osteoinductive indicators were observed for OB: (i) an increased cell count after extract addition indicated a higher proliferation potential; (ii) increased cell sizes after extract supplementation in combination with augmented adhesion behavior of these cells suggest an early switch to differentiation; and (iii) bone-inducing gene expression patterns were determined for all analyzed conditions. The results from the cell lines were inhomogeneous and showed no specific stimulus of Mg. The comparison of the different cell types showed that primary cells of the investigated tissue should be used as an in vitro model if Mg is analyzed. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 165-179, 2017.

Biodegradable Mg alloys are a new class of temporary implant materials for musculo-skeletal surgery. Recent studies show that Mg-based alloys can be biocompatible and there is a high demand to design Mg alloys with adjustable corrosion rates and suitable mechanical properties. An approach to solving this challenge might be the use of Mg metal matrix composites (Mg-MMC). In this study, a Mg-MMC composed of ZK60 was investigated as the base material and hydroxyapatite (HA) particles were added for tailoring its properties. The composite was produced by high-energy ball milling followed by hot extrusion. This processing route was chosen, as HA in contact with molten Mg releases a toxic gas (phosphine – PH3). The HA particles were homogeneously distributed in the ZK60 matrix after ball milling and the composite was consolidated by hot extrusion. This work presents the influence of different amounts of HA on corrosion behavior and mechanical properties of the composite. Corrosion properties were evaluated by immersion and electrochemical measurements in physiological media at 37 °C. A slight improvement in the corrosion resistance was observed for Mg-MMC due to the presence of more stable corrosion products. Compression tests were used to measure the mechanical properties. Under compression, samples showed a slight increase in the compressive yield strength with the addition of HA, while the ultimate strength did not change significantly.

Mg alloys attract more and more attentions for biomedical applications. Mg-Gd alloys were designed as biodegradable implant materials which combine favorable mechanical and corrosion properties. In this work, the microstructure and mechanical properties of binary Mg-2Gd, ternary Mg-2Gd-(Ag, Ca) and quaternary Mg-2Gd-2Ag-0.4Ca alloys were investigated. The alloys were prepared by permanent mould casting. The results show that the additions of Ag and Ca had significant influences on the microstructure and mechanical properties of Mg-2Gd alloy. Ag and Ca additions affect the formation of second phases. A quaternary Mg-Gd-Ag-Ca second phase was found in the quaternary alloy. Both the hardness and tensile yield strength were improved by adding Ag and Ca to 2 wt% Gd-containing alloys due to grain refinement and formation of different intermetallic phases (IMPs). Furthermore, the addition of Ag and Ca can apparently enhance the age hardening of Mg-2Gd alloy.

The goal of this review is to bring to the attention of the readership of Magnesium Research another facet of the importance of magnesium, i.e. magnesium-based biomaterials. A concise history of biomaterials and magnesium are thus presented. In addition, historical and current, clinical magnesium-based applications are presented.

Magnesium based implants could revolutionize applications where orthopedic implants such as nails, screws or bone plates are used because they are load bearing and degrade over time. This prevents a second surgery to remove conventional implants. To improve the biocompatibility we studied here if and for how long a pre-incubation of the material under cell culture conditions is favorable for cell attachment and proliferation. For two materials, Mg and Mg10Gd1Nd, we could show that 6 h pre-incubation are already enough to form a natural protective layer suitable for cell culture.

The corrosion behaviour of as-cast and solution-annealed Mg-0.5Zn-0.2Ca alloy containing 150 ppm Si was investigated in 0.9% NaCl solution. The main secondary phases in the as-cast state are isolated MgCaSi and a coexisting intermetallic particle which consists of Mg2Ca and Ca2Mg6Zn3. A quasi-in situ approach is applied to investigate the corrosion initiation and development. It is proved that Mg2Ca phase is anodic and preferentially corrodes within the first hour of immersion. Whereas, Ca2Mg6Zn3 and MgCaSi phases continuously act as cathodes until 24 h. After solution annealing, the more homogeneous microstructure and reduced galvanic corrosion result in a higher corrosion resistance.

Calcium stearate based super-hydrophobic coating was deposited on plasma electrolytic oxidation (PEO) pre-treated magnesium substrate. The pre-treated magnesium and super-hydrophobic coating covered sample were characterized by scanning electron microscopy, X-ray diffraction and electrochemical corrosion measurements. The cytocompatibility and degradation resistance of magnesium, pre-treated magnesium and super-hydrophobic coating were analysed in terms of cell adhesion and osteoblast differentiation. The results indicate that the calcium stearate top coating shows super-hydrophobicity and that the surface is composed of micro/nanostructure. The super-hydrophobic coating covered sample shows higher barrier properties compared with the PEO pre-treated magnesium and bare magnesium. Human osteoblast proliferation, but not differentiation is enhanced by the PEO coating. Contrary, the super-hydrophobic coating reduces proliferation, but enhances differentiation of osteoblast, observable by the formation of hydroxyapatite. The combination of corrosion protection and cell reaction indicates that this system could be interesting for biomedical applications.

Rare earth element Dy is one of the promising alloying elements for magnesium alloy as biodegradable implants. To understand the effect of Dy in solid solution on the degradation of Mg-Dy alloys in simulated physiological conditions, the present work studied the microstructure and degradation behavior of Mg-Dy alloys in cell culture medium. It is found the corrosion resistance enhances with the increase of Dy content in solid solution in Mg. This can be attributed to the formation of a relatively more corrosion resistant Dy-enriched film which decreases the anodic dissolution of Mg.

Implantation is a frequent procedure in orthopedic surgery, particularly in the aging population. However, it possesses the risk of infection and biofilm formation at the surgical site. This can cause unnecessary suffering to patients and burden on the healthcare system. Pure Mg, as a promising metal for biodegradable orthopedic implants, exhibits some antibacterial effects due to the alkaline pH produced during degradation. However, this antibacterial effect may not be sufficient in a dynamic environment, for example, the human body. The aim of this study was to increase the antibacterial properties under harsh and dynamic conditions by alloying silver metal with pure Mg as much as possible. Meanwhile, the Mg-Ag alloys should not show obvious cytotoxicity to human primary osteoblasts. Therefore, we studied the influence of the microstructure and the silver content on the degradation behavior, cytocompatibility, and antibacterial properties of Mg-Ag alloys in vitro. The results indicated that a higher silver content can increase the degradation rate of Mg-Ag alloys. However, the degradation rate could be reduced by eliminating the precipitates in the Mg-Ag alloys via T4 treatment. By controlling the microstructure and increasing the silver content, Mg-Ag alloys obtained good antibacterial properties in harsh and dynamic conditions but had almost equivalent cytocompatibility to human primary osteoblasts as pure Mg.

Binary magnesium–silver (Mg–Ag) alloys were designed as antibacterial material to treat infections in an implant site. The mechanical and electrochemical measurements were performed on three casting Mg–Ag alloys under cell culture conditions. The composition and distribution of the corrosion layer was analyzed by microscopy and X-ray photoelectron spectroscopy. In cell culture media, Mg–Ag alloys show higher, but still acceptable general corrosion rates while less susceptibility to pitting corrosion than pure Mg with increasing content of silver. This study indicates that Mg–Ag alloys have satisfactory corrosion properties and much better mechanical properties than pure magnesium as a functional biodegradable material.

Biodegradable magnesium (Mg)-based materials are a potential alternative to permanent implants for application in children. Nevertheless effects of those materials on growth plate cartilage and chondrogenesis have not been previously evaluated. In vitro differentiation of ATDC5 cells was evaluated under the influence of pure Mg (PMg), Mg with 10 wt% of gadolinium (Mg-10Gd) and Mg with 2 wt% of silver (Mg-2Ag) degradation products (extracts) and direct cell culture on the materials. Gene expression showed an inhibitory effect on ATDC5 mineralization with the three extracts and a chondrogenic potential of Mg-10Gd. Cells cultured in Mg-10Gd and Mg-2Ag extracts showed the same proliferation and morphology than cells cultured in growth conditions. Mg-10Gd induced an increase in production of ECM and a bigger cell size, similar to the effects found with differentiation conditions. An increased metabolic activity was observed in cells cultured under the influence of Mg-10Gd extracts, indicated by an acidic pH during most of the culture period. After 7 days of culture on the materials, ATDC5 growth, distribution and ECM synthesis were higher on Mg-10Gd samples, followed by Mg-2Ag and PMg, which was influenced by the homogeneity and composition of the degradation layer. This study confirmed the tolerance of ATDC5 cells to Mg-based materials and a chondrogenic effect of Mg-10Gd. Further studies in vitro and in vivo are necessary to evaluate cell reactions to those materials, as well as the effects on bone growth and the biocompatibility of the alloying system in the body.

Magnesium and its alloys gain wide attention as degradable biomaterials. In order to reveal the molecular mechanism of the influence of biodegradable magnesium on cells, proteomics analysis was performed in this work. After mouse fibroblasts (L929) were cultured with or without Mg degradation products (Mg-extract) for 8, 24, and 48 h, changes in protein expression profiles were obtained using isobaric tags for relative and absolute quantitation (iTRAQ) coupled two dimensional liquid chromatography-tandem mass spectrometry (2D LC MS/MS). A total of 867 proteins were identified (relying on at least two peptides). Compared to the control group, 205, 282, and 217 regulated proteins were identified at 8, 24, and 48 h, respectively. 65 common proteins were up or down- regulated within all the three time points, which were involved in various physiological and metabolic activities. Consistent with viability, proliferation, and cell cycle analysis, stimulated energy metabolism as well as protein synthesis pathways were discussed, indicating a possible effect of Mg-extract on L929 proliferation. Furthermore, endocytosis and focal adhesion processes were also discussed. This proteomics study uncovers early cellular mechanisms triggered by Mg degradation products and highlights the cytocompatibility of biodegradable metallic materials for biomedical applications such as stents or orthopaedic implants.