Biodegradable Mg-based Alloys Research Articles

Influence of Noble Metals on the Microstructure and Properties of Biodegradable Mg-Nd-Zr Alloy

In this work, the approach to improve the mechanical properties of a biodegradable Mg-Nd-Zr alloy through modification with noble metals (Ag and Au) was proposed. The separate and combined influence of silver and gold on the macro- and microstructure of the alloy was studied. A qualitative and quantitative assessment of the structural components of the alloy was carried out. It was shown that when modifying the melt, noble metals form the complex intermetallic phases which served as additional crystallization centers. It has been established that adding 0.05 to 0.1 wt.% of noble metals to Mg-based alloy increase the volume fraction of intermetallic compounds by ~1.5 times, shifting them towards smaller size groups with the simultaneous formation of spherical intermetallic compounds. The latter are located in the center of the grain proving them to be the additional nucleation sites. It was shown that complex modification (0.1% Ag + 0.1% Au) of a Mg-based alloy refined its structural components by ~1.5 times, increasing the strength by ~20%, and ductility by ~2 times due to the formation of the intermetallic compounds. The proposed technology for modifying cast biodegradable Mg-based alloys is feasible to be used for the manufacture of implants for osteosynthesis.

Microstructure, Biodegradation, and Mechanical Properties of Biodegradable Mg-Based Alloy Containing Calcium for Biomedical Applications

Microstructure, Biodegradation, and Mechanical Properties of Biodegradable Mg-Based Alloy Containing Calcium for Biomedical Applications

Laser additive manufacturing of magnesium alloys and its biomedical applications

Biomedical magnesium (Mg) alloy with unique biodegradability and excellent biocompatibility is one of the most sought after materials in medical field for orthopedics applications. Nevertheless, the high corrosion rate and inadequate mechanical properties hinder its development. Apart from that, to obtain the best surgical result, the size and shape of the fixation implant need to be adapted to the individual case. Thus, additive manufacturing (AM) processes, such as laser powder bed fusion (LPBF), are used to overcome these issues. This work reviews the recent advancements in biodegradable Mg-based alloys prepared by LPBF for biomedical applications. The influence of feedstock features and manufacturing parameters on the formability and quality is delineated in detail. The mechanical performances, degradation behaviors, and biological behavior of the LPBF-processed parts are discussed. Furthermore, we also made some suggestions for the challenges of Mg alloys in LPBF processing and applications in biomedical.

Mapping knowledge structure and themes trends of biodegradable Mg-based alloy for orthopedic application: A comprehensive bibliometric analysis.

Background: Since Lambotte and Payr first studied Mg-based alloys for orthopedics in 1900, the research of this field has finally ushered in vigorous development in the 21st century. From the perspective of quantitative analysis, this paper clearly demonstrated the global research trend from 2005 to 2021 by using bibliometrics and scientometric analysis. Methods: We obtained the publications from the Web of Science Core Collection (WoSCC) database. The bibliometric and scientometric analysis was conducted by using R software, CiteSpace software, VOSviewer software, Pajek software and Microsoft Excel program. Results: In total, 1921 publications were retrieved. It can be found that the number of publications is gradually increasing year by year. We can find that the most prolific countrie, institution and researcher are China, Chinese Academy of Sciences and Zheng Yufeng, respectively. The most influential journals in this field are Acta Biomaterialia and Biomaterials, with 16,511 and 12,314 total citations, respectively. By conducting the co-cited documents-based clustering analysis, 16 research hotspots and their representative studies have been identified. Besides, by conducting analysis of keywords, we divided the keyword citation bursts representing the development of the field into three stages. Conclusion: The number of researches on the biodegradable Mg-based alloys increased sharply all over the world in the 21st century. China has made significant progress in biodegradable Mg-based alloy research. More focus will be placed on osteogenic differentiation, fabrication, graphene oxide, antibacterial property, bioactive glass and nanocomposite, which may be the next popular topics in the field.

Effect of Ca content on biomineralization of Mg-Ca alloys

The mechanical and physical properties of biodegradable Mg-based alloys make them suitable for temporary orthopaedic implants. However, processing them in such a way that it degrades at the required rate in physiological environment is a challenge. Among the possible methods, in situ formation of calcium phosphate (CaP) during service to control the degradation rate is least explored. The CaP formation can be improved by enhancing the biomineralization of Mg alloys. The present work investigates the effect of Ca concentration (0, 0.5, 1, and 2 wt.%) on the biomineralization of Mg-Ca alloys. Optical microscopy observations and X-ray diffraction analysis showed that Mg-xCa (x = 0.5, 1 & 2 wt. %) alloys were composed of two phases, α-Mg and Mg2Ca. The electrochemical corrosion test in biomimetic NaCl solution and immersion test in simulated body fluid shows that the corrosion rate increases as Ca content increases. The studies reveal that a low calcium content single-phase microstructure is preferred over a multiphase morphology for promoting biomineralization.

Biodegradable Mg-based alloys: biological implications and restorative opportunities

ABSTRACT Mg-based alloys as revolutionary implantable biomaterials have increasingly attracted considerable attention, owing to their biodegradability in vivo and beneficial effects on biological systems. The degradation process and products of Mg-based alloys have been reported to exhibit significant biological effects on host-tissue responses. However, these effects have not yet been fully understood. This review systemically summarizes and analyses the current understandings and recent research progress in this area. The primary focal points are the biological effects and related mechanisms associated with the degradation behaviour of Mg-based alloys. The biological impacts of the degradation products are elucidated and the arguable or controversial issues are also discussed, providing a pathway toward a greater understanding of the biological implications of Mg-based alloys. Furthermore, based on these biological implications, the restorative potential of Mg-based alloys for applications in tissue repair and regeneration is summarized. Finally, outlooks on biosafety evaluation and design strategies for Mg-based alloy implants are briefly discussed.

In vitro degradation and biocompatibility of vitamin C loaded Ca-P coating on a magnesium alloy for bioimplant applications

Molecular recognition was utilized to fabricate bioinspired calcium phosphate (Ca-P) coating on bioabsorbable magnesium alloys through small biomolecules such as Vitamin C (VC). Ca-P and VC hybrid coating (Ca-PVC) was successfully fabricated on AZ31 Mg alloy. The surface morphology and chemical composition of the coatings were investigated using SEM, XRD, and FTIR together with XPS. The results showed that the Ca-PVC coating was composed of bamboo leaf-like Ca-P particles with a thickness of about three times that of the Ca-P coating. The surface roughness of the Ca-PVC coating (1.12 ± 0.12 μm) was lower than that (3.14 ± 1.93 μm) of Ca-P coating, suggesting the formation of refined Ca-P particles resulting from the VC addition. The corrosion resistance of the coated samples was characterized via electrochemical polarization, impedance spectroscopy, and immersion hydrogen evolution tests. The cell toxicity of the coated samples was evaluated utilizing mouse MC3T3-E1 pre-osteoblasts. The charge transfer resistance (Rct) of the Ca-PVC coated alloy increased as compared to the bare and Ca-P coated alloy samples. The Ca-PVC coated alloy exhibited minimal corrosion current density (1.36 × 10−6 A cm−2), which is one order of magnitude lower in comparison to that of the Ca-P coated alloy. These results confirm that VC addition greatly enhanced the coating resistance on AZ31 Mg alloy. It was also noticed that the Ca-PVC coated samples rapidly induced the formation of apatite after immersion in Hank's solution. VC was mainly transformed to L-Threonic acid, which facilitated the nucleation process of the Ca-PVC coating and significantly increased the thickness, density, and bonding strength of the coating. With enhanced corrosion resistance property and excellent biocompatibility, Ca-PVC coating has great potential for application in biodegradable Mg-based alloys.

Laser additive manufacturing of biodegradable Mg-based alloys for biomedical applications: A review

Metallic implants are widely used in internal fixation of bone fracture in surgical treatment. They are mainly used for providing mechanical support and stability during bone reunion, which usually takes a few months to complete. Conventional implants made of stainless steels, Ti-based alloys and CoCrMo alloys have been widely used for orthopedic reconstruction due to their high strength and high corrosion resistance. Such metallic implants will remain permanently inside the body after implantation, and a second surgery after bone healing is needed because the long-term presence of implant will lead to various problems. An implant removal surgery not only incurs expenditure, but also risk and psychological burden. As a consequence, studies on the development of biodegradable implants, which would degrade and disappear in vivo after bone reunion is completed, have drawn researchers’ attention. In this connection, Mg-based alloys have shown great potentials as promising implant materials mainly due to their low density, inherent biocompatibility, biodegradability and mechanical properties close to those of bone. However, the high degradation rate of Mg-based implants in vivo is the biggest hurdle to overcome. Apart from materials selection, a fixation implant is ideally tailor-made in size and shape for an individual case, for best surgical outcomes. Therefore, laser additive manufacturing (LAM), with the advent of sophisticated laser systems and software, is an ideal process to solve these problems. In this paper, we reviewed the progress in LAM of biodegradable Mg-based alloys for biomedical applications. The effect of powder properties and laser processing parameter on the formability and quality was thoroughly discussed. The microstructure, phase constituents and metallurgical defects formed in the LAMed samples were delineated. The mechanical properties, corrosion resistance, biocompatibility and antibacterial properties of the LAMed samples were summarized and compared with samples fabricated by traditional processes. In addition, we have made some suggestions for advancing the knowledge in the LAM of Mg-based alloys for biomedical implants.

Mechanical Alloying Process Applied for Obtaining a New Biodegradable Mg-xZn-Zr-Ca Alloy

The aim of the present paper is to apply the mechanical alloying process to obtain from powder components a new biodegradable Mg-based alloy powder from the system Mg-xZn-Zr-Ca, with high biomechanical and biochemical performance. Various processing parameters for mechanical alloying have been experimented with the ultimate goal to establish an efficient processing route for the production of small biodegradable parts for the medical domain. It has been observed that for the same milling parameters, the composition of the powders has influenced the powder size and shape. On the other hand, for the same composition, the highest experimented milling speed and time conduct to finer powder particles, almost round-shaped, without pores or various inclusions. The most uniform size has been obtained for the powder sample with 10 wt.%Zn. These powders were finally processed by selective laser melting, an additive manufacturing technology, to obtain a homogeneous experimental sample, without cracking, for future more systematical trials.

Microstructure, biodegradation, and mechanical properties of biodegradable Mg-based alloy containing calcium for biomedical applications

Microstructure, biodegradation, and mechanical properties of biodegradable Mg-based alloy containing calcium for biomedical applications

Production of biodegradable Mg-based alloys by mechanical alloying

Mg has several attractive characteristics that make Mg-based materials potentially used for bio-engineering applications. In this work, a ternary Mg-Zn-Ca alloy was manufactured using low energy mechanical alloying (MA) followed by a sintering process under a controlled atmosphere. The aim of this work was to study the effect of milling time on ternary magnesium-zinc-calcium (Mg-Zn-Ca) alloys produced by mechanical alloying. The Mg base alloys were synthesized in a planetary ball mill under an argon atmosphere using stainless steel containers and balls with a milling regimen of 400 rpm for 2, 5 and 10 hours. The alloyed powders obtained by MA at different milling times were characterized by Scanning Electron Microscopy (SEM) and X-ray diffraction (XRD). These results suggest that Mg65Zn30Ca5 and Mg70Zn25Ca5 alloys can be synthesized by mechanical alloying.

The effects of a biodegradable Mg-based alloy on the function of VSMCs via immunoregulation of macrophages through Mg-induced responses.

BackgroundRestenosis is one of the worst side effects of percutaneous coronary intervention (PCI) due to neointima formation resulting from the excessive proliferation and migration of vascular smooth muscle cells (VSMCs) and continuous inflammation. Biodegradable Mg-based alloy is a promising candidate material because of its good mechanical properties and biocompatibility, and biodegradation of cardiovascular stents. Although studies have shown reduced neointima formation after Mg-based CVS implantation in vivo, these findings were inconsistent with in vitro studies, demonstrating magnesium-mediated promotion of the proliferation and migration of VSMCs. Given the vital role of activated macrophage-driven inflammation in neointima formation, along with the well-demonstrated crosstalk between macrophages and VSMCs, we investigated the interactions of a biodegradable Mg-Nd-Zn-Zr alloy (denoted JDBM), which is especially important for cardiovascular stents, with VSMCs via macrophages.MethodsJDBM extracts and MgCl2 solutions were prepared to study their effect on macrophages. To study the effects of the JDBM extracts and MgCl2 solutions on the function of VSMCs via immunoregulation of macrophages, conditioned media (CM) obtained from macrophages was used to establish a VSMC-macrophage indirect coculture system.ResultsOur results showed that both JDBM extracts and MgCl2 solutions significantly attenuated the inflammatory response stimulated by lipopolysaccharide (LPS)-activated macrophages and converted macrophages into M2-type cells. In addition, JDBM extracts and MgCl2 solutions significantly decreased the expression of genes related to VSMC phenotypic switching, migration, and proliferation in macrophages. Furthermore, the proliferation, migration, and proinflammatory phenotypic switching of VSMCs were significantly inhibited when the cells were incubated with CMs from macrophages treated with LPS + extracts or LPS + MgCl2 solutions.ConclusionsTaken together, our results suggested that the magnesium in the JDBM extract could affect the functions of VSMCs through macrophage-mediated immunoregulation, inhibiting smooth muscle hyperproliferation to suppress restenosis after implantation of a biodegradable Mg-based stent.

A homogenous microstructural Mg-based matrix model for orthopedic application with generating uniform and smooth corrosion product layer in Ringer's solution: Study on biodegradable behavior of Mg-Zn alloys prepared by powder metallurgy as a case

Abstract For high corrosion resistance and extensively modified biodegradable Mg-based alloys and composites for bone implants, a new Mg-based matrix model prepared by powder metallurgy is discussed and developed. In this research, Mg-5 wt.%Zn alloys were selected as a case. And they were impacted by hot extrusion and aging treatments to construct microstructure with different characteristics. Their self-forming corrosion product layer in Ringer's solution, biodegradable behavior and corrosion mechanism were minutely investigated by in vitro degradation, electrochemical corrosion and cytocompatibility. The results demonstrated the extruded Mg-5 wt.%Zn alloy aged for 96 h showed high corrosion resistance, good biocompatibility for L929 and excellent ability of maintaining sample integrity during the immersion. Significantly, the alloy showed fine-grain microstructure and uniform distributed hundred nano-sized second phases, which promoted the formation of the uniform and smooth corrosion product layer at the beginning of immersion. The corrosion product layer was more stable in chloride containing aqueous solution and could be directly formed and repaired quickly, which effectively protected the matrix from further corrosion. In addition, an ideal model of Mg-based matrix for bone tissue engineering was tried to presume and propose by discussing the causal relationship between microstructure and bio-corrosion process.

Unexpected cytotoxicity of TiO2-coated magnesium alloys

Biodegradable Mg-based alloys have attracted increasing attention from orthopedic surgeons and biomaterials scientists since their Young’s modulus is close to that of bone. However, control of the degradation rate is still a challenge. Sputtered TiO2 coatings were deposited on Mg-Zn-Ca alloys aiming to reduce the initial strong reactivity of Mg with biological fluids. However, the degradation tests indicated that the coated samples induced a larger variation in the pH, greater H2 production and formation of degradation products in comparison to the bare alloys. Consequently, an enhanced cytotoxicity of the coated samples was observed.

Assessment of Cytotoxicity of Magnesium Oxide and Magnesium Hydroxide Nanoparticles using the Electric Cell-Substrate Impedance Sensing

Magnesium (Mg)-based alloys have the potential for bone repair due to their properties of biodegradation, biocompatibility, and structural stability, which can eliminate the requirement for a second surgery for the removal of the implant. Nevertheless, uncontrolled degradation rate and possible cytotoxicity of the corrosion products at the implant sites are known current challenges for clinical applications. In this study, we assessed in vitro cytotoxicity of different concentrations (0 to 50 mM) of possible corrosion products in the form of magnesium oxide (MgO) and magnesium hydroxide (Mg(OH)2) nanoparticles (NPs) in human fetal osteoblast (hFOB) 1.19 cells. We measured cell proliferation, adhesion, migration, and cytotoxicity using a real-time, label-free, non-invasive electric cell-substrate impedance sensing (ECIS) system. Our results suggest that 1 mM concentrations of MgO/Mg(OH)2 NPs are tolerable in hFOB 1.19 cells. Based on our findings, we propose the development of innovative biodegradable Mg-based alloys for further in vivo animal testing and clinical trials in orthopedics.

The bioeffects of degradable products derived from a biodegradable Mg-based alloy in macrophages via heterophagy

Biodegradable magnesium alloys are promising candidates for use in biomedical applications. However, degradable particles (DPs) derived from Mg-based alloys have been observed in tissue in proximity to sites of implantation, which might result in unexpected effects. Although previous in vitro studies have found that macrophages can take up DPs, little is known about the potential phagocytic pathway and the mechanism that processes DPs in cells. Additionally, it is necessary to estimate the potential bioeffects of DPs on macrophages. Thus, in this study, DPs were generated from a Mg-2.1Nd-0.2Zn-0.5Zr alloy (JDBM) by an electrochemical method, and then macrophages were incubated with the DPs to reveal the potential impact. The results showed that the cell viability of macrophages decreased in a concentration-dependent manner in the presence of DPs due to effects of an apoptotic pathway. However, the DPs were phagocytosed into the cytoplasm of macrophages and further degraded in phagolysosomes, which comprised lysosomes and phagosomes, by heterophagy instead of autophagy. Furthermore, several pro-inflammatory cytokines in macrophages were upregulated by DPs through the induction of reactive oxygen species (ROS) production. To the best of our knowledge, this is the first study to show that DPs derived from a Mg-based alloy are consistently degraded in phagolysosomes after phagocytosis by macrophages via heterophagy, which results in an inflammatory response owing to ROS overproduction. Thus, our research has increased the knowledge of the metabolism of biodegradable Mg metal, which will contribute to an understanding of the health effects of biodegradable magnesium metal implants used for tissue repair. Statement of SignificanceBiomedical degradable Mg-based alloys have great promise in applied medicine. Although previous studies have found that macrophages can uptake degradable particles (DPs) in vitro and observed in the sites of implantation in vivoin vivo, few studies have been carried out on the potential bioeffects relationship between DPs and macrophages. In this study, we analyzed the bioeffects of DPs derived from a Mg-based alloy on the macrophages. We illustrated that the DPs were size-dependently engulfed by macrophages via heterophagy and further degraded in the phagolysosome rather than autophagosome. Furthermore, DPs were able to induce a slight inflammatory response in macrophages by inducing ROS production. Thus, our research enhances the knowledge of the interaction between DPs of Mg-based alloy and cells, and offers a new perspective regarding the use of biodegradable alloys.

A Biodegradable Mg-Based Alloy Inhibited the Inflammatory Response of THP-1 Cell-Derived Macrophages Through the TRPM7-PI3K-AKT1 Signaling Axis.

Mg-based alloys might be ideal biomaterials in clinical applications owing to favorable mechanical properties, biodegradability, biocompatibility, and especially their anti-inflammatory properties. However, the precise signaling mechanism underlying the inhibition of inflammation by Mg-based alloys has not been elucidated. Here, we investigated the effects of a Mg-2.1Nd-0.2Zn-0.5Zr alloy (denoted as JDBM) on lipopolysaccharide (LPS)-induced macrophages. THP-1 cell-derived macrophages were cultured on JDBM, Ti−6Al−4V alloy (Ti), 15% extract of JDBM, and 7.5 mM of MgCl2 for 1 h before the addition of LPS for an indicated time; the experiments included negative and positive controls. Our results showed JDBM, extract, and MgCl2 could decrease LPS-induced tumor necrosis factor (TNF) and interleukin (IL)-6 expression. However, there were no morphologic changes in macrophages on Ti or JDBM. Mechanically, extract and MgCl2 downregulated the expression of toll-like receptor (TLR)-4 and MYD88 compared with the positive control and inhibited LPS-induced nuclear factor-kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways by inactivation of the phosphorylation of IKK-α/β, IKβ-α, P65, P38, and JNK. Additionally, the LPS-induced reactive oxygen species (ROS) expression was also decreased by extract and MgCl2. Interestingly, the expression of LPS-induced TNF and IL-6 could be recovered by knocking down TRPM7 of macrophages, in the presence of extract or MgCl2. Mechanically, the activities of AKT and AKT1 were increased by extract or MgCl2 with LPS and were blocked by a PI3K inhibitor, whereas siRNA TRPM7 inhibited only AKT1. Together, our results demonstrated the degradation products of Mg-based alloy, especially magnesium, and resolved inflammation by activation of the TRPM7–PI3K–AKT1 signaling pathway, which may be a potential advantage or target to promote biodegradable Mg-based alloy applications.

Enhanced corrosion resistance and cytocompatibility of biomimetic hyaluronic acid functionalised silane coating on AZ31 Mg alloy for orthopaedic applications.

This paper reports the corrosion resistant and cytocompatible properties of the hyaluronic acid-silane coating on AZ31 Mg alloy. In this study, the osteoinductive properties of high molecular weight hyaluronic acid (HA, 1-4 MDa) and the corrosion protection of silane coatings were incorporated as a composite coating on biodegradable AZ31 Mg alloy for orthopaedic applications. The multi-step fabrication of coatings first involved dip coating of a passivated AZ31 Mg alloy with a methyltriethoxysilane-tetraethoxysilane sol-gel to deposit a dense, cross-linked and corrosion resistant silane coating (AZ31-MT). The second step was to create an amine-functionalised surface by treating coated alloy with 3-aminopropyl-triethoxy silane (AZ31-MT-A) which facilitated the immobilisation of HA via EDC-NHS coupling reactions at two different concentrations i.e 1 mg.ml-1 (AZ31-MT-A-HA1) and 2 mg.ml-1 (AZ31-MT-A-HA2). These coatings were characterised by Fourier transform infrared spectroscopy, atomic force microscopy and static contact angle measurements which confirmed the successful assembly of the full coatings onto AZ31 Mg alloy. The influence of HA-silane coating on the corrosion of Mg alloy was investigated by electrical impedance spectroscopy and long-term immersion studies measurements in HEPES buffered DMEM. The results showed an enhanced corrosion resistance of HA functionalised silane coated AZ31 substrate over the uncoated equivalent alloy. Furthermore, the cytocompatibility of MC3T3-E1 osteoblasts was evaluated on HA-coated AZ31-MT-A substrates by live-dead staining, quantification of total cellular DNA content, scanning electron microscope and alkaline phosphatase activity. The results showed HA concentration-dependent improvement of osteoblast cellular response in terms of enhanced cell adhesion, proliferation and differentiation. These findings hold great promise in employing such biomimetic multifunctional coatings to improve the corrosion resistance and cytocompatibility of biodegradable Mg-based alloy for orthopaedic applications.

Evolution of the microstructure and fracture characteristics of a Mg-Nd-Zn-Zr-Mn alloy through heat treatment and extrusion

Appropriate mechanical properties are essential for the use of biodegradable Mg-based alloys as structurally supporting materials. However, research studies on the evolution of the tensile fracture pathways and fracture characteristics of as-cast and as-extruded Mg-based alloys are limited. In this paper, the microstructures, tensile properties, fracture pathways and fracture characteristics of the as-cast, heat treated and hot-extruded Mg-1.59Nd-2.91Zn-0.05Zr-0.35Mn (NZKM) alloys were systematically investigated. The results indicated that the hot-extruded NZKM alloy exhibits good mechanical properties with a yield strength and an elongation reaching 212 MPa and 30.7%, respectively. These excellent properties were attributed to its special multiscale microstructure consisting of an α-Mg matrix (2–10 μm), eutectic compound β-Mg4Zn7 (2–10 μm) together with a high density of dispersed nanoscale precipitates, that provide solid solution strengthening, grain boundary strengthening and precipitation strengthening effects. The fracture patterns changed with the evolution of the microstructures. Intergranular and transgranular cleavage fractures were changed to ductile fractures by hot extrusion.

Corrosion behavior of biodegradable Mg-based alloys via femtosecond laser surface melting

The effects of femtosecond (fs) laser treatment on a biocompatible Mg-Ca-Zn alloy were systemically analyzed. The fs laser altered the surface microstructure of the Mg-Ca-Zn alloy, resulting in reduced corrosion through localized melting and rapid solidification. Treatment with appropriate laser energy (500 Hz) generated an exceptionally thin modified layer (∼2 μm) with a uniformly refined microstructure. Laser-induced remelting of the secondary phase reduced galvanic corrosion and prevented the occurrence of pitting corrosion, resulting in overall reduced corrosion. Results reveal that the corrosive nature of the biodegradable Mg alloy can be controlled through surface modification by a fs laser.