Degradable Magnesium Research Articles

Mechanical, degradation and cytocompatibility properties of magnesium coated phosphate glass fibre reinforced polycaprolactone composites.

Retention of mechanical properties of phosphate glass fibre reinforced degradable polyesters such as polycaprolactone and polylactic acid in aqueous media has been shown to be strongly influenced by the integrity of the fibre/polymer interface. A previous study utilising 'single fibre' fragmentation tests found that coating with magnesium improved the fibre and matrix interfacial shear strength. Therefore, the aim of this study was to investigate the effects of a magnesium coating on the manufacture and characterisation of a random chopped fibre reinforced polycaprolactone composite. Short chopped strand non-woven phosphate glass fibre mats were sputter coated with degradable magnesium to manufacture phosphate glass fibre/polycaprolactone composites. The degradation behaviour (water uptake, mass loss and pH change of the media) of these polycaprolactone composites as well as of pure polycaprolactone was investigated in phosphate buffered saline. The Mg coated fibre reinforced composites revealed less water uptake and mass loss during degradation compared to the non-coated composites. The cations released were also explored and a lower ion release profile for all three cations investigated (namely Na(+), Mg(2+) and Ca(2+)) was seen for the Mg coated composite samples. An increase of 17% in tensile strength and 47% in tensile modulus was obtained for the Mg coated composite samples. Both flexural and tensile properties were investigated and a higher retention of mechanical properties was obtained for the Mg coated fibre reinforced composite samples up to 10 days immersion in PBS. Cytocompatibility study showed both composite samples (coated and non-coated) had good cytocompatibility with human osteosarcoma cell line.

Development and degradation behavior of magnesium scaffolds coated with polycaprolactone for bone tissue engineering

Rapid degradation of magnesium (Mg) alloys is the major drawback preventing these materials from being applicable as tissue engineering scaffolds. In order to resolve this issue, in this paper, porous Mg scaffolds coated by polycaprolactone (PCL) were synthesized and their material properties and in vitro biodegradation were fully examined. The results indicated that PCL coating can significantly enhance the compressive strength and degradation resistance of Mg scaffolds. We showed that while the uncoated Mg scaffold degrades completely (100% weight loss) after 72h, the degradation (weight loss) of the Mg scaffolds coated by 3% and 6% PCL is only 36% and 23%, respectively. Thus PCL-coated Mg scaffolds, as a biodegradable metal scaffold, can potentially have a promising application in bone tissue engineering.

The effect of metallic magnesium degradation products on osteoclast-induced osteolysis and attenuation of NF-κB and NFATc1 signaling

Wear particle-induced aseptic prosthetic loosening is one of the most common reasons for total joint arthroplasty (TJA). Extensive bone destruction (osteolysis) by osteoclasts plays an important role in wear particle-induced peri-implant loosening. Thus, strategies for inhibiting osteoclast function may have therapeutic benefit for prosthetic loosening. Here, we mimicked the process of magnesium (Mg) degradation in vivo and obtained Mg leach liquor (MLL) by immersing pure Mg in culture medium. For the first time, we demonstrated that MLL suppresses osteoclast formation, polarization, and osteoclast bone resorption in vitro. An in vivo assay demonstrated that MLL attenuates wear particle-induced osteolysis. Furthermore, we found that MLL significantly inhibits nuclear factor-κB (NF-κB) activation by retarding inhibitor-κB degradation and subsequent NF-κB nuclear translocation. We also found that MLL attenuates the expression of NFATc1 at both the protein and mRNA levels. These results demonstrate that MLL has anti-osteoclast activity in vitro and prevents wear particle-induced osteolysis in vivo. Collectively, our study suggests that metallic magnesium, one of the orthopedic implants with superior properties, has significant potential for the treatment of osteolysis-related diseases caused by excessive osteoclast formation and function.

Cytotoxic Effect on Osteosarcoma MG-63 Cells by Degradation of Magnesium

Biocompatible and biodegradable magnesium (Mg) based metals have attracted great interest for use in orthopedic implants and devices. Based on our previous study that Mg with and without micro-arc oxidation (MAO) coating showed obvious cytotoxic effect on tumor cells due to the increase of pH value during the degradation of Mg, this study further evaluated the cytotoxic effect of Mg and MAO coated Mg on osteosarcoma (MG-63) cells by analyzing the cell adhesion, morphology and number through observation of scanning electron microscope, as well as live/dead staining, lactate dehydrogenase (LDH) activity and 4, 6-diamidino-2-phenylindole (DAPI) assay. The results indicated that, compared to titanium, Mg could strongly inhibit the cell adherence, morphology and number of MG-63 on the surface of the naked Mg, whereas the MAO coated Mg showed relative weak cytotoxic effect on MG-63 cells, expecting that magnesium based metals with suitable coating can be designed to be applied as tumor prosthesis in the clinical practice.

POLYMER IODINATION FOR IMPROVED IN VITRO TRACKING OF BIODEGRADABLE STENT DEGRADATION: SERIAL MICROCT IMAGING FOR BIOREACTOR TESTING

Evaluating the in vitro degradation of a biodegradable magnesium (Mg) alloy stent by X-ray micro-computed tomography (CT) is made difficult by low attenuation of Mg and polymer coating. Addition of iodine (I) to polymer coating of Mg stents was investigated to improve segmentation of microCT images

Friction stir processing of magnesium–nanohydroxyapatite composites with controlled in vitro degradation behavior

Nano-hydroxyapatite (nHA) reinforced magnesium composite (Mg–nHA) was fabricated by friction stir processing (FSP). The effect of smaller grain size and the presence of nHA particles on controlling the degradation of magnesium were investigated. Grain refinement from 1500μm to ≈3.5μm was observed after FSP. In vitro bioactivity studies by immersing the samples in supersaturated simulated body fluid (SBF 5×) indicate that the increased hydrophilicity and pronounced biomineralization are due to grain refinement and the presence of nHA in the composite respectively. Electrochemical test to assess the corrosion behavior also clearly showed the improved corrosion resistance due to grain refinement and enhanced biomineralization. Using MTT colorimetric assay, cytotoxicity study of the samples with rat skeletal muscle (L6) cells indicate marginal increase in cell viability of the FSP-Mg–nHA sample. The composite also showed good cell adhesion.

The effects of poly(3,4-ethylenedioxythiophene) coating on magnesium degradation and cytocompatibility with human embryonic stem cells for potential neural applications

Magnesium (Mg) is a promising conductive metallic biomaterial due to its desirable mechanical properties for load bearing and biodegradability in human body. Controlling the rapid degradation of Mg in physiological environment continues to be the key challenge toward clinical translation. In this study, we investigated the effects of conductive poly(3,4-ethylenedioxythiophene) (PEDOT) coating on the degradation behavior of Mg substrates and their cytocompatibility. Human embryonic stem cells (hESCs) were used as the in vitro model system to study cellular responses to Mg degradation because they are sensitive and can potentially differentiate into many cell types of interest (e.g., neurons) for regenerative medicine. The PEDOT was deposited on Mg substrates using electrochemical deposition. The greater number of cyclic voltammetry (CV) cycles yielded thicker PEDOT coatings on Mg substrates. Specifically, the coatings produced by 2, 5, and 10 CV cycles (denoted as 2×-PEDOT-Mg, 5×-PEDOT-Mg, and 10×-PEDOT-Mg) had an average thickness of 31, 63, and 78 µm, respectively. Compared with non-coated Mg samples, all PEDOT coated Mg samples showed slower degradation rates, as indicated by Tafel test results and Mg ion concentrations in the post-culture media. The 5×-PEDOT-Mg showed the best coating adhesion and slowest Mg degradation among the tested samples. Moreover, hESCs survived for the longest period when cultured with the 5×-PEDOT-Mg samples compared with the non-coated Mg and 2×-PEDOT-Mg. Overall, the results of this study showed promise in using PEDOT coating on biodegradable Mg-based implants for potential neural recording, stimulation and tissue engineering applications, thus encouraging further research.

Biodegradation of a magnesium alloy implant in the intercondylar femoral notch showed an appropriate response to the synovial membrane in a rabbit model in vivo

Degradable magnesium alloys are promising biomaterials for orthopedic applications. The aim of this study was to evaluate the potential effects on both the synovial membrane (synovialis) and the synovial fluid (synovia) of the degradation products of a MgYREZr-pin implanted in the intercondylar femoral notch in a rabbit model. Thirty-six animals were randomized into two groups (MgYREZr or Ti6Al4V alloy) of 18 animals each. Each group was then divided into three subgroups with implantation periods of 1, 4, and 12 weeks, with six animals in each subgroup. The initial inflammatory reaction caused by the surgical trauma declined after 12 weeks of implantation, and elucidated a progressive recovery of the synovial membrane. Compared with control Ti6Al4V pins, there were no significant differences between the groups. However, after 12 weeks, recovery of the synovial membrane was more advanced in the titanium group, in which 92% showed no signs of synovitis, than in the magnesium group. A cytotoxicity test with L929 cells and human osteoblasts (HOB) was also conducted, according to EN ISO 10993-5/12, and no toxic leachable products were observed after 24 h of incubation. In conclusion, the MgYREZr alloy seems to be a suitable material for intra-articular degradable implants.

First-Principles Study on the Corrosion Mechanism of Degradable Medical Mg Alloys in the Medium Containing Cl-

A first-principles plane-wave pseudopotential method based on Density Functional Theory (DFT) has been used to perform a comparative theoretical study of the adsorption H2O and Cl- on a degradable medical Mg alloy (0001) surface. It is found that H2O molecules bind preferentially at atop sites with a large tilt angle away from the surface normal, Cl- ions are energetically favoured adsorbed on hcp hollow sites. In the aqueous solution containing Cl-, the preferential adsorption of Cl- over H2O on Mg surface prevents the Mg surface passivation and induces the corrosion of degradable medical Mg alloys. For H2O adsorption, the ineraction between H2O molecule and Mg surface makes Mg hydration, and thereby Mg alloy surface passivates and the formation of the protective Mg(OH)2. For Cl- ion adsorption, a 0.44e charge translation from Cl- ion to the Mg alloy surface makes the corrosion potential of Mg alloy surface negativly shifted. Thereby, the activity and the corrosion of magnesium alloy are enhanced. This can explain why degradable medical magnesium alloys corrode quickly in physiological media containing high concentrations of chloride ions.

Correction: An In Vitro Mechanism Study on the Proliferation and Pluripotency of Human Embryonic Stems Cells in Response to Magnesium Degradation

Correction: An In Vitro Mechanism Study on the Proliferation and Pluripotency of Human Embryonic Stems Cells in Response to Magnesium Degradation

Nano-hydroxyapatite reinforced AZ31 magnesium alloy by friction stir processing: a solid state processing for biodegradable metal matrix composites

Friction stir processing (FSP) was successfully adopted to fabricate nano-hydroxyapatite (nHA) reinforced AZ31 magnesium alloy composite as well as to achieve fine grain structure. The combined effect of grain refinement and the presence of embedded nHA particles on enhancing the biomineralization and controlling the degradation of magnesium were studied. Grain refinement from 56 to ~4 and 2 μm was observed at the stir zones of FSP AZ31 and AZ31-nHA composite respectively. The immersion studies in super saturated simulated body fluid (SBF 5×) for 24 h suggest that the increased wettability due to fine grain structure and nHA particles present in the AZ31-nHA composite initiated heterogeneous nucleation which favored the early nucleation and growth of calcium-phosphate mineral phase. The nHA particles as nucleation sites initiated rapid biomineralization in the composite. After 72 h of immersion the degradation due to localized pitting was observed to be reduced by enhanced biomineralization in both the FSPed AZ31 and the composite. Also, best corrosion behavior was observed for the composite before and after immersion test. MTT assay using rat skeletal muscle (L6) cells showed negligible toxicity for all the processed and unprocessed samples. However, cell adhesion was observed to be more on the composite due to the small grain size and incorporated nHA.

Magnesium degradation products: Effects on tissue and human metabolism

Owing to their mechanical properties, metallic materials present a promising solution in the field of resorbable implants. The magnesium metabolism in humans differs depending on its introduction. The natural, oral administration of magnesium via, for example, food, essentially leads to an intracellular enrichment of Mg(2+) . In contrast, introducing magnesium-rich substances or implants into the tissue results in a different decomposition behavior. Here, exposing magnesium to artificial body electrolytes resulted in the formation of the following products: magnesium hydroxide, magnesium oxide, and magnesium chloride, as well as calcium and magnesium apatites. Moreover, it can be assumed that Mg(2+) , OH(-) ions, and gaseous hydrogen are also present and result from the reaction for magnesium in an aqueous environment. With the aid of physiological metabolic processes, the organism succeeds in either excreting the above mentioned products or integrating them into the natural metabolic process. Only a burst release of these products is to be considered a problem. A multitude of general tissue effects and responses from the Mg's degradation products is considered within this review, which is not targeting specific implant classes. Furthermore, common alloying elements of magnesium and their hazardous potential in vivo are taken into account.

An In Vitro Mechanism Study on the Proliferation and Pluripotency of Human Embryonic Stems Cells in Response to Magnesium Degradation

Magnesium (Mg) is a promising biodegradable metallic material for applications in cellular/tissue engineering and biomedical implants/devices. To advance clinical translation of Mg-based biomaterials, we investigated the effects and mechanisms of Mg degradation on the proliferation and pluripotency of human embryonic stem cells (hESCs). We used hESCs as the in vitro model system to study cellular responses to Mg degradation because they are sensitive to toxicants and capable of differentiating into any cell types of interest for regenerative medicine. In a previous study when hESCs were cultured in vitro with either polished metallic Mg (99.9% purity) or pre-degraded Mg, cell death was observed within the first 30 hours of culture. Excess Mg ions and hydroxide ions induced by Mg degradation may have been the causes for the observed cell death; hence, their respective effects on hESCs were investigated for the first time to reveal the potential mechanisms. For this purpose, the mTeSR®1 hESC culture media was either modified to an alkaline pH of 8.1 or supplemented with 0.4–40 mM of Mg ions. We showed that the initial increase of media pH to 8.1 had no adverse effect on hESC proliferation. At all tested Mg ion dosages, the hESCs grew to confluency and retained pluripotency as indicated by the expression of OCT4, SSEA3, and SOX2. When the supplemental Mg ion dosages increased to greater than 10 mM, however, hESC colony morphology changed and cell counts decreased. These results suggest that Mg-based implants or scaffolds are promising in combination with hESCs for regenerative medicine applications, providing their degradation rate is moderate. Additionally, the hESC culture system could serve as a standard model for cytocompatibility studies of Mg in vitro, and an identified 10 mM critical dosage of Mg ions could serve as a design guideline for safe degradation of Mg-based implants/scaffolds.

Zone coulometry and ion-release analysis of degradable magnesium alloys

Zone coulometry and determination of ion release of an electrolyte from anodic polarization measurements are the established calculation modes for the electrochemical behavior of dental and biomedical alloys. The aim of the study was to compare the electrochemical corrosion behavior of six different experimental magnesium alloys without manganese using artificial plasma (AP) and in phosphate-buffered saline (PBS−) as simulated body fluids through anodic polarization measurements. In addition, determination of the magnesium release of the electrolytes was performed using inductively coupled plasma optical emission spectrometry and zone coulometry. Six specimens were prepared from each alloy. Anodic polarization measurements ranging from –150 mV ~Ecorrto –1200 mV were performed with both of the electrolytes. From each measurement, corrosion current density, the breakdown or pitting potential and its corresponding current density, zero potential, the polarization resistance, the corrosion rate were calculated. The magnesium release of the electrolytes was compared with the calculated values using Faraday’s law. For zone coulometry, five different trials were completed, and the electrical charge was calculated for each potential range of all magnesium alloys tested and for both electrolytes. Lower corrosion values were found in AP than in PBS−for all measurements. However, the rankings of the alloys are similar in both the electrolytes. Zone coulometry using small potential ranges and determination of ion release can be additional evaluation tools for magnesium alloys.

Bio-functional Design for Metal Implants, a New Concept for Development of Metallic Biomaterials

A new concept for development of metallic biomaterials is proposed in this article, i.e., a certain bio-function can be realized for a metal implant through continuous release of a designed bio-functional metal element from surface of the metal implant in the body environment. This creative idea has been verified to be possible by several different in vitro and in vivo experimental evidences on the Cu-bearing stainless steels and magnesium based metals. It was indicated that a trace amount of Cu release from the Cu-bearing steels could have obvious bio-functions of reduction of the in-stent restenosis (ISR), anti-bacterial infection, inhibiting the inflammatory cells and even promoting the early osteogenesis. Furthermore, the degradation of magnesium based metals in bones could promote the new bone formation, enhance the bone mineral density for the osteoporosis modeled animal, and even have strong anti-bacterial ability and strong cytotoxicity to bone tumor cells due to the enhancement of pH. Special bio-function with satisfied load-bearing capacity for metallic biomaterials will bring higher application values for the implant made of this novel material. This is an attractive direction for research and development with many challenges, but the final success will be much beneficial to the majority of patients.

Nanostructured hydroxyapatite/poly(lactic-co-glycolic acid) composite coating for controlling magnesium degradation in simulated body fluid

Biodegradable magnesium (Mg) and its alloys have many attractive properties (e.g. comparable mechanical properties to cortical bone) for orthopedic implant applications, but they degrade too rapidly in the human body to meet clinical requirements. Nanostructured hydroxyapatite (nHA)/poly(lactic-co-glycolic acid) (PLGA) composite coatings provide synergistic properties for controlling degradation of Mg-based substrates and improving bone–implant integration. In this study, nHA/PLGA composites were spin coated onto Mg-based substrates and the results showed that the nHA/PLGA coatings retained nano-scale features with nHA dispersed in PLGA matrix. In comparison with non-coated Mg, the nHA/PLGA composite coated Mg increased the corrosion potential and decreased the corrosion current in revised simulated body fluid (rSBF). After 24 h of immersion in rSBF, increased calcium phosphate (CaP) deposition and formation of Mg-substituted CaP rosettes were observed on the surface of the nHA/PLGA coated Mg, indicating greater bioactivity. In contrast, no significant CaP was deposited on the PLGA coated Mg. Since both PLGA coating and nHA/PLGA coating showed some degree of delamination from Mg-based substrates during extended immersion in rSBF, the coating processing and properties should be further optimized in order to take full advantage of biodegradable Mg and nHA/PLGA nanocomposites for orthopedic applications.

Comparative biomechanical and radiological characterization of osseointegration of a biodegradable magnesium alloy pin and a copolymeric control for osteosynthesis

Magnesium alloys offer great advantages as degradable implant material for pediatric fracture fixation and hold the potential to overcome certain critical shortcomings inherent to currently used degradable (co)polymers. Besides good biocompatibility and appropriate degradation kinetics, sufficient implant anchorage in host bone is critical to prevent implant failure. Bone-implant anchorage of biodegradable magnesium alloys, however, has not yet been related and compared to that of copolymers, their degradable counterparts currently in clinical use. The aim of this study, therefore, was to comparatively assess bone-implant interface strength and the amount of peri-implant bone of a biodegradable magnesium alloy pin (Mg-Y-Nd-HRE) and a self-reinforced copolymeric control (85/15 poly(l-lactic-co-glycolic acid)). To this purpose, push-out testing, microfocus computed tomography (μCT), histological and scanning electron microscopic examination was performed after 4, 12 and 24 weeks of transcortical implantation in 72 rats. Biomechanical testing revealed significantly higher ultimate shear strength for the magnesium alloy pins than for the copolymeric controls at all 3 timepoints (P≤0.001 for all comparisons). As evaluated by μCT, the amount of bone present near the interface and in a wider radius (up to 0.5mm) around it was higher in the magnesium alloy implants at 4 weeks, without significant differences at 12 and 24 weeks. Histological examination confirmed direct bone-to-implant contact for both implant types. In vivo degradation of implants did not induce any noticeable local or systemic inflammation. This data suggests that the investigated degradable magnesium alloy rod exhibits markedly superior bone-implant interface strength and a greater amount of peri-implant bone than a self-reinforced copolymeric control currently in use; thus it fulfills a crucial prerequisite for its successful clinical deployment as an alternative degradable orthopedic implant material. Further studies, however, are warranted to evaluate the long-term degradation behavior and biocompatibility of the investigated degradable magnesium-based alloy.

A Study on Factors Affecting the Degradation of Magnesium and a Magnesium-Yttrium Alloy for Biomedical Applications

Controlling degradation of magnesium or its alloys in physiological saline solutions is essential for their potential applications in clinically viable implants. Rapid degradation of magnesium-based materials reduces the mechanical properties of implants prematurely and severely increases alkalinity of the local environment. Therefore, the objective of this study is to investigate the effects of three interactive factors on magnesium degradation, specifically, the addition of yttrium to form a magnesium-yttrium alloy versus pure magnesium, the metallic versus oxide surfaces, and the presence versus absence of physiological salt ions in the immersion solution. In the immersion solution of phosphate buffered saline (PBS), the magnesium-yttrium alloy with metallic surface degraded the slowest, followed by pure magnesium with metallic or oxide surfaces, and the magnesium-yttrium alloy with oxide surface degraded the fastest. However, in deionized (DI) water, the degradation rate showed a different trend. Specifically, pure magnesium with metallic or oxide surfaces degraded the slowest, followed by the magnesium-yttrium alloy with oxide surface, and the magnesium-yttrium alloy with metallic surface degraded the fastest. Interestingly, only magnesium-yttrium alloy with metallic surface degraded slower in PBS than in DI water, while all the other samples degraded faster in PBS than in DI water. Clearly, the results showed that the alloy composition, presence or absence of surface oxide layer, and presence or absence of physiological salt ions in the immersion solution all influenced the degradation rate and mode. Moreover, these three factors showed statistically significant interactions. This study revealed the complex interrelationships among these factors and their respective contributions to degradation for the first time. The results of this study not only improved our understanding of magnesium degradation in physiological environment, but also presented the key factors to consider in order to satisfy the degradation requirements for next-generation biodegradable implants and devices.

Degradation and antibacterial properties of magnesium alloys in artificial urine for potential resorbable ureteral stent applications

This article presents an investigation on the effectiveness of magnesium and its alloys as a novel class of antibacterial and biodegradable materials for ureteral stent applications. Magnesium is a lightweight and biodegradable metallic material with beneficial properties for use in medical devices. Ureteral stent is one such example of a medical device that is widely used to treat ureteral canal blockages clinically. The bacterial colony formation coupled with the encrustation on the stent surface from extended use often leads to clinical complications and contributes to the failure of indwelling medical devices. We demonstrated that magnesium alloys decreased Escherichia coli viability and reduced the colony forming units over a 3-day incubation period in an artificial urine (AU) solution when compared with currently used commercial polyurethane stent. Moreover, the magnesium degradation resulted in alkaline pH and increased magnesium ion concentration in the AU solution. The antibacterial and degradation properties support the potential use of magnesium-based materials for next-generation ureteral stents. Further studies are needed for clinical translation of biodegradable metallic ureteral stents.

Evaluation of magnesium‐yttrium alloy as an extraluminal tracheal stent

Tracheomalacia is a relatively rare problem, but can be challenging to treat, particularly in pediatric patients. Due to the presence of mechanically deficient cartilage, the trachea is unable to resist collapse under physiologic pressures of respiration, which can lead to acute death if left untreated. However, if treated, the outcome for patients with congenital tracheomalacia is quite good because the cartilage tends to spontaneously mature over a period of 12 to 18 months. The present study investigated the potential for the use of degradable magnesium-3% yttrium alloy (W3) to serve as an extraluminal tracheal stent in a canine model. The host response to the scaffold included the formation of a thin, vascularized capsule consisting of collagenous tissue and primarily mononuclear cells. The adjacent cartilage structure was not adversely affected as observed by bronchoscopic, gross, histologic, and mechanical analysis. The W3 stents showed reproducible spatial and temporal fracture patterns, but otherwise tended to corrode quite slowly, with a mix of Ca and P rich corrosion product formed on the surface and observed focal regions of pitting. The study showed that the approach to use degradable magnesium alloys as an extraluminal tracheal stent is promising, although further development of the alloys is required to improve the resistance to stress corrosion cracking and improve the ductility.