Increased use of titanium alloys as biomaterials is occurring due to their lower modulus, superior biocompatibility and enhanced corrosion resistance when compared to more conventional stainless steels and cobalt-based alloys. These attractive properties were a driving force for the early introduction of alpha (cpTi) and alpha + beta (Ti-6A1-4V) alloys as well as for the more recent development of new Ti-alloy compositions and orthopaedic metastable beta titanium alloys. The later possess enhanced biocompatibility, reduced elastic modulus, and superior strain-controlled and notch fatigue resistance. However, the poor shear strength and wear resistance of titanium alloys have nevertheless limited their biomedical use. Although the wear resistance of beta-Ti alloys has shown some improvement when compared to alpha + beta alloys, the ultimate utility of orthopaedic titanium alloys as wear components will require a more complete fundamental understanding of the wear mechanisms involved. This review examines current information on the physical and mechanical characteristics of titanium alloys used in artifical joint replacement prostheses, with a special focus on those issues associated with the long-term prosthetic requirements, e.g., fatigue and wear.

Porous titanium alloys have been used for biomedical implants owing to their low-modulus matching with that of human bones and interconnecting pores with suitable size, which facilitates bone in-growth and satisfies the requirement of a successful implant. Recently, additive manufacturing (3D printing) has emerged as an excellent technology for manufacturing porous implants with accurate designed pore parameters and overcoming processing difficulties caused by high melting temperatures of metals. In this paper, the microstructure and mechanical properties of porous Ti-6Al-4V, commercial pure titanium (CP-Ti), and low-modulus Ti2448 alloys produced by 3D printing, obtained mainly by the authors' group, are reviewed. For Ti-6Al-4V, its fatigue properties are affected by the type of mesh struts and post processing. The better fatigue life of CP-Ti compared to that of Ti-6Al-4V derives from its superior ductility and the strain hardening effect caused by deformation twins. The excellent fatigue life of the low-modulus Ti2448 alloy results from its superelasticity and the high toughness, which increases the crack nucleation life and fatigue crack propagation life, respectively. Future directions of corrosion-fatigue properties of materials in complex physiological environments, surface biological functionalization, and porous material of new metallic alloy systems are discussed.

钛合金多孔材料具有与人体骨匹配的弹性模量，可有效解决金属植入物与人体骨弹性错配；其内部存在的大量孔隙有利于周围细胞的长入和新骨的生长，从而促进骨组织形成。近年来，增材制造(3D打印)技术被用于钛合金多孔材料制备，该方法可以精确控制孔隙参数，并且克服了因金属高熔点造成的制备困难。本文综述了作者团队在3D打印医用Ti-6Al-4V、纯Ti以及低模量钛合金多孔材料组织及力学性能的研究结果。对于Ti-6Al-4V两相合金，其疲劳性能受多孔结构设计和多种后处理的影响。纯Ti多孔材料较Ti-6Al-4V更优的疲劳寿命源于其更好的塑性和形变孪晶的应变硬化效应。低模量Ti2448合金的优异疲劳寿命则源于其超弹性提高裂纹萌生寿命，高韧性提高裂纹扩展寿命。最后展望了复杂生理环境腐蚀疲劳性能、多孔材料表面生物活化处理和新型医用金属体系多孔材料等发展方向。

Medical application materials must meet multiple requirements, and the designed implant must mimic the bone structure in shape and support the formation of bone tissue (osteogenesis). Magnesium (Mg) alloys, as a "smart" biodegradable material and as "the green engineering material in the twenty-first century", have become an outstanding bone implant material due to their natural degradability, smart biocompatibility, and desirable mechanical properties. Magnesium is recognised as the next generation of orthopaedic appliances and bioresorbable scaffolds. At the same time, improving the mechanical properties and corrosion resistance of magnesium alloys is an urgent challenge to promote the application of magnesium alloys. Nevertheless, the excessively quick deterioration rate generally results in premature mechanical integrity disintegration and local hydrogen build-up, resulting in restricted clinical bone restoration applicability. The condition of Mg bone implants is thoroughly examined in this study. The relevant approaches to boost the corrosion resistance, including purification, alloying treatment, surface coating, and Mg-based metal matrix composite, are comprehensively revealed. These characteristics are reviewed to assess the progress of contemporary Mg-based biocomposites and alloys for biomedical applications. The fabricating techniques for Mg bone implants also are thoroughly investigated. Notably, laser-based additive manufacturing fabricates customised forms and complicated porous structures based on its distinctive additive manufacturing conception. Because of its high laser energy density and strong controllability, it is capable of fast heating and cooling, allowing it to modify the microstructure and performance. This review paper aims to provide more insight on the present challenges and continued research on Mg bone implants, highlighting some of the most important characteristics, challenges, and strategies for improving Mg bone implants.© 2022. The Author(s), under exclusive licence to Islamic Azad University.

Magnesium alloys, with good biocompatibility and mechanical-compatibility, can be developed as next generation promising biomaterials. This paper summerizes the principle and the cutting-edge advances of alloying of magnesium alloys as degradable biomaterials. The effects of alloy elements on the material and biological properties of magnesium alloys are analyzed. The focus is laid on the influence of microstructure (grain size, secondary phase or intermetallic compound, long-period stacking ordered (LPSO) phase and quasi-crystal phase), heat treatment and surface oxide film on degradation and their critical progress on corrosion morphology and mechanism. Several outlooks on bio-magnesium alloys are proposed.

镁合金具有良好的生物相容性和力学相容性,具有发展成为新一代可降解生物材料的前景。本文总结了医用镁合金合金化的原理与进展,分析了合金元素对镁合金材料学以及生物学性能的影响,重点讨论了医用镁合金显微组织(晶粒尺寸、第二相、长周期堆垛有序相(LPSO)、准晶相)、热处理和表面氧化膜对其降解行为的影响和腐蚀形态、机理方面的重要进展,并指出了医用镁合金的发展方向。

The 2015 Dietary Guidelines Advisory Committee indicated that magnesium was a shortfall nutrient that was underconsumed relative to the Estimated Average Requirement (EAR) for many Americans. Approximately 50% of Americans consume less than the EAR for magnesium, and some age groups consume substantially less. A growing body of literature from animal, epidemiologic, and clinical studies has demonstrated a varied pathologic role for magnesium deficiency that includes electrolyte, neurologic, musculoskeletal, and inflammatory disorders; osteoporosis; hypertension; cardiovascular diseases; metabolic syndrome; and diabetes. Studies have also demonstrated that magnesium deficiency is associated with several chronic diseases and that a reduced risk of these diseases is observed with higher magnesium intake or supplementation. Subclinical magnesium deficiency can exist despite the presentation of a normal status as defined within the current serum magnesium reference interval of 0.75-0.95 mmol/L. This reference interval was derived from data from NHANES I (1974), which was based on the distribution of serum magnesium in a normal population rather than clinical outcomes. What is needed is an evidenced-based serum magnesium reference interval that reflects optimal health and the current food environment and population. We present herein data from an array of scientific studies to support the perspective that subclinical deficiencies in magnesium exist, that they contribute to several chronic diseases, and that adopting a revised serum magnesium reference interval would improve clinical care and public health.© 2016 American Society for Nutrition.

Purpose: Nondegradable steel-and titanium-based implants are commonly used in orthopedic surgery. Although they provide maximal stability, they are also associated with interference on imaging modalities, may induce stress shielding, and additional explantation procedures may be necessary. Alternatively, degradable polymer implants are mechanically weaker and induce foreign body reactions. Degradable magnesium-based stents are currently being investigated in clinical trials for use in cardiovascular medicine. The magnesium alloy MgYREZr demonstrates good biocompatibility and osteoconductive properties. The aim of this prospective, randomized, clinical pilot trial was to determine if magnesium-based MgYREZr screws are equivalent to standard titanium screws for fixation during chevron osteotomy in patients with a mild hallux valgus.;Methods: Patients (n=26) were randomly assigned to undergo osteosynthesis using either titanium or degradable magnesium-based implants of the same design. The 6 month follow-up period included clinical, laboratory, and radiographic assessments.;Results: No significant differences were found in terms of the American Orthopaedic Foot and Ankle Society (AOFAS) score for hallux, visual analog scale for pain assessment, or range of motion (ROM) of the first metatarsophalangeal joint (MTPJ). No foreign body reactions, osteolysis, or systemic inflammatory reactions were detected. The groups were not significantly different in terms of radiographic or laboratory results.;Conclusion: The radiographic and clinical results of this prospective controlled study demonstrate that degradable magnesium-based screws are equivalent to titanium screws for the treatment of mild hallux valgus deformities.

Mg is a typical biodegradable metal widely used for biomedical applications due to its considerable mechanical properties and bioactivity. Biodegradable polymers have attracted great interest owing to their favorable processability and inclusiveness. However, it is challenging for the degradation rates of Mg or polymers to precisely match tissue repair processes, and the significant changes in local pH during degradation hinder tissue repair. The concept of combining Mg with polymers is proposed to overcome the shortcomings of materials, aiming to meet repair needs from various aspects such as mechanics and biology. Therefore, it is essential to systematically understand the behavior of biodegradable Mg/polymer composite (BMPC) from the design, manufacturing, mechanical properties, degradation, and biological effects. In this review, we elaborate on the design concepts and manufacturing strategies of high-strength BMPC, the "structure-function" relationship between the microstructures and mechanical properties of composites, the variation in the degradation rate due to endogenous and exogenous factors, and the establishment of advanced degradation research platform. Additionally, the interplay among composite components during degradation and the biological function of composites under non-responsive/stimuli-responsive platforms are also discussed. Finally, we hope that this review will benefit future clinical applications of "structure-function" integrated biomaterials.© 2024 The Authors.

The last decade has seen a significant growth in the market for alloys used for implants, especially for those intended for orthopedic implants. Research into biodegradable magnesium-based alloys has made great strides in this period, so huge progress has been made in their use in the medical industry. The important factors that led to the intensification of research in this regard, were social but also economic, wanting to improve the quality of life, by reducing the use of conventionally permanent metallic implants (stainless steel, cobalt-based alloys, and titanium alloys) which involve the second implant removal surgery and other undesirable effects (stress shielding and metal ion releases), with a negative impact on the emotional and physical condition of patients, and by significantly reducing the costs for both the patient and the health system in the field of orthopedics. This paper refers to the impact and importance of biodegradable Mg alloys, reviewing the beginning of their development, the significant characteristics that make them so desirable for such applications (orthopedic implants) but also the characteristics that must be modulated (corrosion rate and mechanical properties) to arrive at the ideal product for the targeted application. It highlights, in detail, the mechanism and aspects related to the corrosion behaviour of Mg alloys, electrochemical characterization techniques / methods, as well as strategies to improve the corrosion behaviour and mechanical properties of these types of biodegradable alloys. The means of optimization, the category and the effect of the alloying elements, the design criteria, the requirements that the implants of biodegradable alloys Mg-based must meet and the aspects related to their efficiency are also presented. Finally, the potential applications in the specialized clinics, as well as the final products currently used and made by important prestigious companies in the world are approached. (C) 2021 Chongqing University. Publishing services provided by Elsevier B.V. on behalf of KeAi Communications Co. Ltd.

Magnesium alloys have gained increasing attention for biomedical applications due to their biocompatibility and the biodegradability. Hydroxyapatite (HA) is known to be a highly bioactive because of its similar chemical and crystallographic structures to bone. Therefore, HA is believed to be a potential ceramic material for the fabrication of Mg based composites, to combine the advantages of both Mg and HA. But, in general, the composites known to be more susceptible to corrosion attack than the matrix alloy. Hence, in the present work, Sn is used as an alloying element to evaluate its effect on mechanical as well as corrosion properties of Mg/HA composites. Mg with 5 wt% HA and Mg-1 wt% Sn-5 wt% HA composites were prepared separately by stir assisted squeeze casting route. The phase analysis and microstructure were characterized by X-ray diffraction (XRD) and scanning electron microscope (SEM) coupled with energy dispersive spectroscopy (EDS) respectively. Mechanical properties were evaluated by conducting the compression and micro hardness tests. Corrosion properties of as-cast composites were studied by linear polarization, Tafel and electrochemical impedance spectroscopy (EIS) techniques. The results of both XRD and SEM-EDS revealed that the main constitutional phases of as-cast Mg/HA composites were alpha-Mg and HA whereas, in Mg-Sn/HA composites, the phase Mg2Sn was observed along with fine distribution of HA particles. In both the cases, no interfacial reactions observed. The yield strength, ultimate compression strength and hardness were found to be increased with the addition of Sn in Mg/HA composites. Furthermore, the addition of Sn also played an important role in increasing the corrosion resistance of the Mg/HA composites which was attributed the refinement of grain size and the formation of Mg 2 Sn phase along the grain boundaries. Hence, it was concluded that the addition of Sn improves both mechanical and corrosion properties of Mg/HA composites. (C) 2019 Published by Elsevier B.V. on behalf of Chongqing University.

Significant progress has been made in magnesium-based composites during recent decades, especially for the appearance of magnesium matrix composite reinforced by nanoparticles. The nanoparticles added not only exhibit a good strengthening effect, but also maintain the initial toughness of the matrix, effectively balancing the contradiction between the strength and plasticity in the traditional magnesium matrix composites. The magnesium matrix nanocomposites with excellent mechanical properties have pushed the development of magnesium matrix composites to a new stage. However, it is very difficult to disperse the nanoparticles in metal melt especially in magnesium melt which is different from other metal melts and dangerous during the cast processing. This means that the preparation of magnesium matrix nanocomposite is extremely challenging. Further, the magnesium matrix nanocomposites possess a distinctive characteristic in deformation behavior, strengthening and toughening mechanism due to their special size effect of nanoparticles. Accordingly, this review will focus on the new preparation technologies, deformation behavior, mechanical properties and strengthening and toughening mechanisms. The potential applications, development trends and future research ideas of magnesium matrix nanocomposite are also prospected. (C) 2020 Published by Elsevier B.V. on behalf of Chongqing University.

In this work, graphene nanoplatelets (GNPs) reinforced magnesium (Mg) matrix composites were synthesised using the multi-step dispersion route. Well-dispersed but inhomogeneously distributed GNPs were obtained in the matrix. Compared with the monolithic alloy, the nanocomposites exhibited dramatically enhanced Young's modulus, yield strength and ultimate tensile strength and relatively high plasticity, which mainly attributed to the significant heterogeneous laminated microstructure induced by the addition of GNPs. With increasing of the concentration of GNPs, mechanical properties of the composites were gradually improved. Especially, the strengthening efficiency of all the composites exceeded 100%, which was significantly higher than that of carbon nanotubes reinforced Mg matrix composites. The grain refinement and load transfer provided by the two-dimensional and wrinkled surface structure of GNPs were the dominated strengthening mechanisms of the composites. This investigation develops a new method for incorporating GNPs in metals for fabricating high-performance composites.

This work introduces Mg-4Zn-3Gd-1Ca/2ZnO (wt.%) nanocomposite fabricated using the technique of disintegrated melt deposition and extrusion. Addition of ZnO nanoparticles enhanced the compressive strengths of alloy by similar to 100 MPa. Nanocomposite samples display high strength and good ductility: 0.2% compressive yield stress of 355 MPa, ultimate compressive stress of 703 MPa, and compressive failure strain of 10.6%. The significant enhancement of compressive yield stress is mainly attributed to the grain refinement by adding nanoparticles. The strength levels exceed that of commercial magnesium alloys (i.e. WE43, WE54, ZK60, and ME21) and mild steels (i.e. S275 and S355), making Mg-4Zn-3Gd-1Ca/2ZnO a very promising material for multiple engineering and biomedical applications.

Mg alloys are attractive in the fields of aerospace, automotive, and biomedical engineering, owing to the advantages of light weight, high specific strength, excellent damping property, good biocompatibility, and in vivo degradable property. However, conventional methods for manufacturing Mg alloys, such as casting and deformation processing, yield low-quality large-scale monolithic and complex structures, which hinder the applications of Mg parts. Additive manufacturing (AM) is a burgeoning alternative to manufacture monolithic parts through layer-by-layer deposition of metallic materials using 3D model data. In this paper, the latest research progress in AM of Mg alloys, which focuses on technological processes and influencing factors, macro and microstructures, mechanical properties, and corrosion properties of parts manufactured primarily by selective laser melting (SLM) and wire and arc AM (WAAM), are comprehensively reviewed. Currently, additively manufactured Mg parts with a relative density > 99% have been achievable through both SLM and WAAM after process optimization, and their mechanical properties and corrosion resistance have been comparable to those of casting and wrought parts, indicating a great potential for engineering applications. Finally, the future development trend and research direction of AM of Mg alloys are proposed from the perspectives of materials design, process improvement, and performance evaluation.

镁合金具有轻质、比强度高、阻尼减振、生物相容性好、体内可降解等优点，在航空航天、汽车轻量化、生物医疗等领域应用潜力巨大。然而传统的镁合金铸造成形和变形加工技术在制备一体化复杂结构件上具有一定的局限性，制约了镁合金在上述领域的应用普及。增材制造是一种根据三维模型数据逐层熔化沉积的先进技术，有望成为镁合金复杂构件制备的重要技术途径。本文概述了近年来增材制造镁合金的研究进展，重点对选区激光熔化(SLM)和电弧增材制造(WAAM) 2种主要增材制造的工艺研发现状和影响因素、微观组织、力学性能及耐蚀行为进行分析与总结。研究表明，工艺优化后SLM和WAAM等技术均可获得致密度> 99%的镁合金试件，并且能够获得与传统制造镁合金相当的力学性能和耐蚀性能，增材制造镁合金表现出极大的工程应用潜力。最后，从材料优化、工艺改进及性能评价等方面对增材制造在镁合金中的未来发展趋势与研究方向进行了总结与展望。

Selective laser melting (SLM) additive manufacturing technology holds the broad prospect for the preparation of high-performance complex metal components owing to its high processing accuracy, short manufacturing cycle, and high material usage. Magnesium (Mg) alloys are the lightest metal structural material and provide the benefits of low density, substantial specific strength and specific stiffness, good damping and shock absorption performance, and good biodegradability. Thus, it is worthwhile to employ SLM to manufacture Mg alloys, which is predicted to widen the application scope of Mg alloys. In this study, a comprehensive review on SLM of Mg alloys focusing on the preparation of Mg alloy powders, SLM process parameters, metallurgical defects, microstructure and mechanical properties of the as-built state, post-processing, and special equipment developed for SLM of Mg alloys is given. Finally, the future development trends of the SLM of Mg alloys are explored.

选区激光熔化(SLM)增材制造技术由于其加工精度高、制造周期短、材料利用率高等优点，在制备高性能复杂金属构件方面具有广阔的应用前景。镁合金是最轻的金属结构材料，具有密度低、比强度和比刚度高、阻尼减震性能好、生物降解性良好等优点。因此，采用SLM技术制备镁合金具有重要的研究价值，有望拓宽镁合金的应用范围。本文针对镁合金SLM增材制造技术，详细介绍了镁合金粉末制备、SLM工艺参数、冶金缺陷、SLM态的显微组织和力学性能、后处理、镁合金专用SLM设备方面的研究进展，并展望了未来镁合金SLM研究的发展方向。

Recently, there is a growing interest in developing magnesium (Mg) based degradable biomaterial. Although corrosion is a concern for Mg, other physical properties, such as low density and Young's modulus, combined with good biocompatibility, lead to significant research and development in this area. To address the issues of corrosion and low yield strength of pure Mg, several approaches have been adopted, such as, composite preparation with suitable bioactive reinforcements, alloying, or surface modifications. This review specifically focuses on recent developments in Mg-based metal matrix composites (MMCs) for biomedical applications. Much effort has gone into finding suitable bioactive, bioresorbable reinforcements and processing techniques that can improve upon existing materials. In summary, this review provides a comprehensive overview of existing Mg-based composite preparation and their mechanical and corrosion properties and biological responses and future perspectives on the development of Mg-based composite biomaterials.

Magnesium (Mg) and some of its alloys have attracted extensive interests for biomedical applications as they exhibit biodegradability and low elastic modulus that is closer to natural bones than the currently used metallic implant materials such as titanium (Ti) and its alloys, stainless steels, and cobalt-chromium (Co-Cr) alloys. However, the rapid degradation of Mg alloys and loss of their mechanical integrity before sufficient bone healing impede their clinical application. Our literature review shows that magnesium matrix nanocomposites (MMNCs) reinforced with nanoparticles possess enhanced strength, high corrosion resistance, and good biocompatibility. This article provides a detailed analysis of the effects of nanoparticle reinforcements on the mechanical properties, corrosion behavior, and biocompatibility of MMNCs as promising biodegradable implant materials. The governing equations to quantitatively predict the mechanical properties and underlying synergistic strengthening mechanisms in MMNCs are elucidated. The potential, recent advances, challenges and future research directions in relation to nanoparticles reinforced MMNCs are highlighted. STATEMENT OF SIGNIFICANCE: Critically reviewing magnesium metal matrix nanocomposites (MMNCs) for the biomedical application. Clear definitions of strengthening mechanisms using reinforcement particle in the magnesium matrix, as there were controversial in governing equations of strengthening parameters. Providing better understanding of the effect of particle size, volume fraction, interfacial bonding, and uniform dispersion of reinforcement particles on MMNCs.Copyright © 2019 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Designing and preparation of magnesium alloys with adjustable biocorrosion rates in the human body and precipitation ability of bone-like apatite layer have been of interest recently. Application of metal matrix composites (MMC) based on magnesium alloys might be an approach to this challenge. The aim of this work was fabrication and evaluation of biocorrosion and bioactivity of a novel MMC made of magnesium alloy AZ91 as matrix and fluorapatite (FA) nano particles as reinforcement. Biodegradable Magnesium-nano fluorapatite metal matrix nanocomposite (AZ91-20FA) was made via a blending-pressing-sintering method. In vitro corrosion tests were performed for evaluation of biocorrosion behavior of produced AZ91-20FA nanocomposite. The results showed that the addition of FA nano particles to magnesium alloy can reduce not only the corrosion rate in a simulated body environment but also accelerate the formation of an apatite layer.

Mg and Mg-HAP composites containing 5, 10 and 15 wt% of hydroxyapatite have been produced following a powder metallurgy route that consists of mixing raw powders and consolidation by extrusion. The microstructure, texture, mechanical behavior and resistance to corrosion under a PBS solution have been studied. Addition of HAP increases the microhardness of the composites, however the yield strength under compression slightly decreases. Texture analyses reveal a fiber texture for pure Mg that is weakened increasing the HAP fraction. This texture promotes twinning and softening of Mg and Mg-5HAP during the initial deformation stages. Mg-10HAP and Mg-15HAP present a strain-hardening dependence showing no softening. The volume fraction of HAP particles weakens the texture and favors the activation of secondary slip systems. Corrosion experiments in PBS solution have shown that Mg-5HAP exhibits the best resistance to corrosion. Texture and porosity appear to be the main material features controlling the corrosion rates of Mg-HAP composites under the present conditions.Copyright © 2014 Elsevier Ltd. All rights reserved.

Magnesium alloys are well known for their low density, high specific strength. However, they are often limited by unsatisfactory mechanical properties. To meet the challenge of growing demand for light structural applications, metal matrix composites (MMCs) have attracted more attention. Carbon nanotubes (CNTs) have attracted much attention as the ideal reinforcements for MMCs due to their excellent mechanical strength and Young's modulus. In this work, 0.1%CNTs/AZ91 (mass fraction) magnesium matrix composites were prepared by low temperature powder metallurgy and hot extrusion. The magnesium alloy and composites were observed and analyzed by SEM, XRD and TEM. The room temperature mechanical properties of the composites were tested by Instron 5982 machine. The results showed that the CNTs distributed uniformly in the composites. The CNTs have an effect on reducing grain size, promoting precipitation of β-Mg17Al12 and weakening basal texture. The compressive strength and yield strength of the composites reached 617 and 445 MPa, which increased by 8.8% and 7.2%, respectively. The tensile strength and yield strength were 393 and 352 MPa, which 4.5% and 6.0% MPa higher than the matrix, respectively. It can be found that fine grain strengthening and load transfer play a leading role in improving the strength in the 0.1%CNTs/AZ91 magnesium matrix composites.

采用低温粉末冶金及热挤压工艺制备了具有超细晶组织的0.1%CNTs/AZ91 (质量分数)镁基复合材料。通过SEM、XRD、TEM对镁基复合材料的微观组织进行了表征，并对其室温力学性能进行测试。结果表明：CNTs在复合材料中分布均匀，CNTs的加入使得复合材料的晶粒尺寸从0.552 μm细化到0.346 μm，并促进了β相的析出，同时弱化了基面织构。复合材料的抗压强度和屈服强度分别达到了617和445 MPa，较基体提高了8.8%和7.2%；其抗拉强度和屈服强度分别达到了393和352 MPa，与基体相比分别提高了4.5%和6.0%。对强化机制进行分析，发现细晶强化和载荷传递是0.1%CNTs/AZ91复合材料的主要强化机制。

Development of biodegradable implants has grown into one of the important areas in medical science. Degradability becomes more important for orthopaedic accessories used to support fractured and damaged bones, in order to avoid second surgery for their removal after healing. Clinically available biodegradable orthopaedic materials are mainly made of polymers or ceramics. These orthopaedic accessories have an unsatisfactory mechanical strength, when used in load-bearing parts. Magnesium and its alloys can be suitable candidate for this purpose, due to their outstanding strength to weight ratio, biodegradability, non-toxicity and mechanical properties, similar to natural bone. The major drawback of magnesium is its low corrosion resistance, which also influences its mechanical and physical characteristics in service condition. An effort has been taken in this research to improve the corrosion resistance, bioactivity and mechanical strength of biodegradable magnesium alloys by synthesizing Mg-3wt% Zn matrix composite, reinforced with thermally treated hydroxyapatite(HA) [Ca(PO)(OH)], a bioactive and osteogenic ceramic. Addition of 5wt% HA is found effective in reducing the corrosion rate by 42% and improvement in the compressive yield strength of biodegradable magnesium alloy by 23%. In-vitro evaluation, up to 56 days, reveal improved resistance to degradation with HA reinforcement to Mg. Osteoblast cells show better growth and proliferation on HA reinforced surfaces of the composite. Mg-HA composite structure shows impressive potential to be used in orthopaedic fracture fixing accessories.Copyright © 2017 Elsevier Ltd. All rights reserved.

Recent studies indicate that there is a high demand to design magnesium alloys with adjustable corrosion rates and suitable mechanical properties. An approach to this challenge might be the application of metal matrix composite (MMC) based on magnesium alloys. In this study, a MMC made of magnesium alloy AZ91D as a matrix and hydroxyapatite (HA) particles as reinforcements have been investigated in vitro for mechanical, corrosive and cytocompatible properties. The mechanical properties of the MMC-HA were adjustable by the choice of HA particle size and distribution. Corrosion tests revealed that HA particles stabilised the corrosion rate and exhibited more uniform corrosion attack in artificial sea water and cell solutions. The phase identification showed that all samples contained hcp-Mg, Mg(17)Al(12), and HA before and after immersion. After immersion in artificial sea water CaCO3 was found on MMC-HA surfaces, while no formation of CaCO3 was found after immersion in cell solutions with and without proteins. Co-cultivation of MMC-HA with human bone derived cells (HBDC), cells of an osteoblasts lineage (MG-63) and cells of a macrophage lineage (RAW264.7) revealed that RAW264.7, MG-63 and HBDC adhere, proliferate and survive on the corroding surfaces of MMC-HA. In summary, biodegradable MMC-HA are cytocompatible biomaterials with adjustable mechanical and corrosive properties.

Interference screw in the fixation of autologous tendon graft to the bone tunnel is widely accepted for the reconstruction of anterior cruciate ligament (ACL), but the regeneration of fibrocartilaginous entheses could hardly be achieved with the traditional interference screw. In the present work, biodegradable high-purity magnesium (HP Mg) showed good cytocompatibility and promoted the expression of bone morphogenetic protein-2 (BMP-2) and vascular endothelial growth factor (VEGF), fibrocartilage markers (Aggrecan, COL2A1 and SOX-9), and glycosaminoglycan (GAG) production in vitro. The HP Mg screw was applied to fix the semitendinosus autograft to the femoral tunnel in a rabbit model of ACL reconstruction with titanium (Ti) screw as the control. The femur-tendon graft-tibia complex was retrieved at 3, 6, 9 and 12 weeks. Gross observation and range of motion (ROM) of the animal model reached normal levels at 12 weeks. No sign of host reaction was found in the X-ray scanning. The HP Mg group was comparable to the Ti group with respect to biomechanical properties of the reconstructed ACL, and the ultimate load to failure and stiffness increased 12 weeks after surgery. In the histological analysis, the HP Mg group formed distinct fibrocartilage transition zones at the tendon-bone interface 12 weeks after surgery, whereas a disorganized fibrocartilage layer was found in the Ti group. In the immunohistochemical analysis, highly positive staining of BMP-2, VEGF and the specific receptor for BMP-2 (BMPR1A) was shown at the tendon-bone interface of the HP Mg group compared with the Ti group. Furthermore, the HP Mg group had significantly higher expression of BMP-2 and VEGF than the Ti group in the early phase of tendon-bone healing, followed by enhanced expression of fibrocartilage markers and GAG production. Therefore we proposed that the stimulation of BMP-2 and VEGF by Mg ions was responsible for the fibrochondrogenesis of Mg materials. HP Mg was promising as a biodegradable interference screw with the potential to promote fibrocartilaginous entheses regeneration in ACL reconstruction. Copyright © 2015 Elsevier Ltd. All rights reserved.

How to enhance tendon graft incorporation into bone tunnels for achieving satisfactory healing outcomes in patients with anterior cruciate ligament reconstruction (ACLR) is one of the most challenging clinical problems in orthopaedic sports medicine. Several studies have recently reported the beneficial effects of Mg implants in bone fracture healing, indicating the use potential of Mg devices in promoting the tendon graft osteointegration. Here, we developed an innovative Mg-based interference screws for fixation of the tendon graft in rabbits underwent ACLR and investigated the biological role of Mg-based implants in the graft healing. The titanium (Ti) interference screw was used as the control. We demonstrated that Mg interference screw significantly accelerated the incorporation of the tendon graft into bone tunnels via multiscale analytical methods including scanning electronic microscopy/energy dispersive spectrometer (SEM/EDS), micro-hardness, micro-Fourier transform infrared spectroscopy (μFTIR), and histology. Our in vivo study showed that Mg implants enhanced the recruitment of bone marrow stromal stem cells (BMSCs) towards peri-implant bone tissue, which may be ascribed to the upregulation of local TGF-β1 and PDGF-BB. Besides, the in vitro study revealed that higher Mg ions was beneficial to the improvement of capability in cell adhesion and osteogenic differentiation of BMSCs. Thus, the enhancement in cell migration, cell adhesion and osteogenic differentiation of BMSCs may contribute to an improved tendon graft osteointegration in the Mg group. Our findings in this work may further facilitate clinical applications of Mg-based interference screws for enhancing tendon graft-bone junction healing in patients indicated for ACLR.How to promote tendon-bone junction healing is one of the major challenging issues for satisfactory clinical outcomes in patients after ACL reconstruction. The improvement of bony ingrowth into the tendon graft-bone interface can enhance the tendon graft osteointegration. In this study, we applied Mg based interference screws to fix the tendon graft in rabbits and found the use of Mg screws could accelerate and significantly increase mineralized matrix formation at the tendon-bone interface in animals when compared to those with Ti screws. We elucidated the mechanism behind the favorable effects of Mg screws on the graft healing in both in vitro and in vivo studies from multiscale technologies. The optimized interface structure and function in Mg group may be ascribed to the improved cell migration capability, enhanced cell adhesion strength and promoted osteogenic differentiation ability of BMSCs under the stimuli of Mg ions degraded from implanted Mg screws. Our findings may help us broaden our thinking in the application potential of Mg interference screws in future clinical trials.Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Each year, millions of Americans suffer bone fractures, often requiring internal fixation. Current devices, like plates and screws, are made with permanent metals or resorbable polymers. Permanent metals provide strength and biocompatibility, but cause long-term complications and may require removal. Resorbable polymers reduce long-term complications, but are unsuitable for many load-bearing applications. To mitigate complications, degradable magnesium (Mg) alloys are being developed for craniofacial and orthopedic applications. Their combination of strength and degradation make them ideal for bone fixation. Previously, we conducted a pilot study comparing Mg and titanium devices with a rabbit ulna fracture model. We observed Mg device degradation, with uninhibited healing. Interestingly, we observed bone formation around degrading Mg, but not titanium, devices. These results highlighted the potential for these fixation devices. To better assess their efficacy, we conducted a more thorough study assessing 99.9% Mg devices in a similar rabbit ulna fracture model. Device degradation, fracture healing, and bone formation were evaluated using microcomputed tomography, histology and biomechanical tests. We observed device degradation throughout, and calculated a corrosion rate of 0.40±0.04mm/year after 8 weeks. In addition, we observed fracture healing by 8 weeks, and maturation after 16 weeks. In accordance with our pilot study, we observed bone formation surrounding Mg devices, with complete overgrowth by 16 weeks. Bend tests revealed no difference in flexural load of healed ulnae with Mg devices compared to intact ulnae. These data suggest that Mg devices provide stabilization to facilitate healing, while degrading and stimulating new bone formation.Copyright © 2015 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Intramedullary stabilization is frequently used to treat long bone fractures. Implants usually remain unless complications arise. Since implant removal can become technically very challenging with the potential to cause further tissue damage, biodegradable materials are emerging as alternative options. Magnesium (Mg)-based biodegradable implants have a controllable degradation rate and good tissue compatibility, which makes them attractive for musculoskeletal research. Here we report for the first time the implantation of intramedullary nails made of an Mg alloy containing 2% silver (Mg2Ag) into intact and fractured femora of mice. Prior in vitro analyses revealed an inhibitory effect of Mg2Ag degradation products on osteoclast differentiation and function with no impair of osteoblast function. In vivo, Mg2Ag implants degraded under non-fracture and fracture conditions within 210days and 133days, respectively. During fracture repair, osteoblast function and subsequent bone formation were enhanced, while osteoclast activity and bone resorption were decreased, leading to an augmented callus formation. We observed a widening of the femoral shaft under steady state and regenerating conditions, which was at least in part due to an uncoupled bone remodeling. However, Mg2Ag implants did not cause any systemic adverse effects. These data suggest that Mg2Ag implants might be promising for intramedullary fixation of long bone fractures, a novel concept that has to be further investigated in future studies.Biodegradable implants are promising alternatives to standard steel or titanium implants to avoid implant removal after fracture healing. We therefore developed an intramedullary nail using a novel biodegradable magnesium-silver-alloy (Mg2Ag) and investigated the in vitro and in vivo effects of the implants on bone remodeling under steady state and fracture healing conditions in mice. Our results demonstrate that intramedullary Mg2Ag nails degrade in vivo over time without causing adverse effects. Importantly, radiographs, μCT and bone histomorphometry revealed a significant increase in callus size due to an augmented bone formation rate and a reduced bone resorption in fractures supported by Mg2Ag nails, thereby improving bone healing. Thus, intramedullary Mg2Ag nails are promising biomaterials for fracture healing to circumvent implant removal.Copyright © 2016 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

A bioresorbable, mono-crystalline magnesium (Mg) ring device and suture implantation technique were designed to connect the ends of a transected anterior cruciate ligament (ACL) to restabilize the knee and load the ACL to prevent disuse atrophy of its insertion sites and facilitate its healing. To test its application, cadaveric goat stifle joints were evaluated using a robotic/universal force-moment sensor testing system in three states: Intact, ACL-deficient, and after Mg ring repair, at 30°, 60°, and 90° of joint flexion. Under a 67-N anterior tibial load simulating that used in clinical examinations, the corresponding anterior tibial translation (ATT) and in-situ forces in the ACL and medial meniscus for 0 and 100 N of axial compression were obtained and compared with a control group treated with suture repair. In all cases, Mg ring repair reduced the ATT by over 50% compared to the ACL-deficient joint, and in-situ forces in the ACL and medial meniscus were restored to near normal levels, showing significant improvement over suture repair. These findings suggest that Mg ring repair could successfully stabilize the joint and load the ACL immediately after surgery, laying the framework for future in vivo studies to assess its utility for ACL healing. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:2001-2008, 2016.© 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

Magnesium alloys are promising biomaterials for orthopedic implants because of their degradability, osteogenic effects, and biocompatibility. Magnesium has been proven to promote distraction osteogenesis. However, its mechanism of promoting distraction osteogenesis is not thoroughly studied. In this work, a high-purity magnesium pin developed and applied in rat femur distraction osteogenesis. Mechanical test, radiological and histological analysis suggested that high-purity magnesium pin can promote distraction osteogenesis and shorten the consolidation time. Further RNA sequencing investigation found that alternative Wnt signaling was activated. In further bioinformatics analysis, it was found that the Hedgehog pathway is the upstream signaling pathway of the alternative Wnt pathway. We found that Ptch protein is a potential target of magnesium and verified by molecular dynamics that magnesium ions can bind to Ptch protein. In conclusion, HP Mg implants have the potential to enhance bone consolidation in the DO application, and this process might be via regulating Ptch protein activating Hedgehog-alternative Wnt signaling.© 2020 [The Author/The Authors].

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 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.

Biocompatibility is a key issue in the development of new implant materials. In this context, a novel class of biodegrading Mg implants exhibits promising properties with regard to inflammatory response and mechanical properties. The interaction between Mg degradation products and the nanoscale structure and mineralization of bone, however, is not yet sufficiently understood. Investigations by synchrotron microbeam x-ray fluorescence (μXRF), small angle x-ray scattering (μSAXS) and x-ray diffraction (μXRD) have shown the impact of degradation speed on the sites of Mg accumulation in the bone, which are around blood vessels, lacunae and the bone marrow. Only at the highest degradation rates was Mg found at the implant-bone interface. The Mg inclusion into the bone matrix appeared to be non-permanent as the Mg-level decreased after completed implant degradation. μSAXS and μXRD showed that Mg influences the hydroxyl apatite (HAP) crystallite structure, because markedly shorter and thinner HAP crystallites were found in zones of high Mg concentration. These zones also exhibited a contraction of the HAP lattice and lower crystalline order. Copyright © 2015 Elsevier Ltd. All rights reserved.

The aim of this study was to gain an understanding on the collective cellular effects of magnesium (Mg) corrosion products on the behaviour of cells responsible for bone formation and remodelling. The response of mesenchymal stem cells (MSCs) and osteoclast cells to both soluble (Mg ions) and insoluble (granule) corrosion products were recapitulated in vitro by controlling the concentration of the corrosion products. Clearance of corrosion granules by MSCs was also inspected by TEM analysis at sub-cellular level. The effect of Mg corrosion products varied depending on the state of differentiation of cells, concentration and length of exposure. The presence of the corrosion products significantly altered the cells' metabolic and proliferative activities, which further affected cell fusion/differentiation. While cells tolerated higher than physiological range of Mg concentration (16 mM), concentrations below 10 mM were beneficial for cell growth. Furthermore, MSCs were shown to contribute to the clearance of intercellular corrosion granules, whilst high concentrations of corrosion products negatively impacted on osteoclast progenitor cell number and mature osteoclast cell function.

Orthopedic implants containing biodegradable magnesium have been used for fracture repair with considerable efficacy; however, the underlying mechanisms by which these implants improve fracture healing remain elusive. Here we show the formation of abundant new bone at peripheral cortical sites after intramedullary implantation of a pin containing ultrapure magnesium into the intact distal femur in rats. This response was accompanied by substantial increases of neuronal calcitonin gene-related polypeptide-α (CGRP) in both the peripheral cortex of the femur and the ipsilateral dorsal root ganglia (DRG). Surgical removal of the periosteum, capsaicin denervation of sensory nerves or knockdown in vivo of the CGRP-receptor-encoding genes Calcrl or Ramp1 substantially reversed the magnesium-induced osteogenesis that we observed in this model. Overexpression of these genes, however, enhanced magnesium-induced osteogenesis. We further found that an elevation of extracellular magnesium induces magnesium transporter 1 (MAGT1)-dependent and transient receptor potential cation channel, subfamily M, member 7 (TRPM7)-dependent magnesium entry, as well as an increase in intracellular adenosine triphosphate (ATP) and the accumulation of terminal synaptic vesicles in isolated rat DRG neurons. In isolated rat periosteum-derived stem cells, CGRP induces CALCRL- and RAMP1-dependent activation of cAMP-responsive element binding protein 1 (CREB1) and SP7 (also known as osterix), and thus enhances osteogenic differentiation of these stem cells. Furthermore, we have developed an innovative, magnesium-containing intramedullary nail that facilitates femur fracture repair in rats with ovariectomy-induced osteoporosis. Taken together, these findings reveal a previously undefined role of magnesium in promoting CGRP-mediated osteogenic differentiation, which suggests the therapeutic potential of this ion in orthopedics.

Magnesium alloys are being investigated for load-bearing bone fixation devices due to their initial mechanical strength, modulus similar to native bone, biocompatibility and ability to degrade in vivo. Previous studies have found Mg alloys to support bone regeneration in vivo, but the mechanisms have not been investigated in detail. In this study, we analyzed the effects of Mg(2+) stimulation on intracellular signaling mechanisms of human bone marrow stromal cells (hBMSCs). hBMSCs were cultured in medium containing 0.8, 5, 10, 20 and 100mM MgSO4, either with or without osteogenic induction factors. After 3weeks, mineralization of extracellular matrix (ECM) was analyzed by Alizarin red staining, and gene expression was analyzed by quantitative polymerase chain reaction array. Mineralization of ECM was enhanced at 5 and 10mM MgSO4, and collagen type X mRNA (COL10A1, an ECM protein deposited during bone healing) expression was increased at 10mM MgSO4 both with and without osteogenic factors. We also confirmed the increased production of collagen type X protein by Western blotting. Next, we investigated the mechanisms of intracellular signaling by analyzing the protein production of hypoxia-inducible factor (HIF)-1α and 2α (transcription factors of COL10A1), vascular endothelial growth factor (VEGF) (activated by HIF-2α) and peroxisome proliferator-activated receptor gamma coactivator (PGC)-1α (transcription coactivator of VEGF). We observed that 10mM MgSO4 stimulation enhanced COL10A1 and VEGF expression, possibly via HIF-2α in undifferentiated hBMSCs and via PGC-1α in osteogenic cells. These data suggest possible ECM proteins and transcription factors affected by Mg(2+) that are responsible for the enhanced bone regeneration observed around degradable Mg orthopedic/craniofacial devices.Copyright © 2014. Published by Elsevier Ltd.

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.Copyright © 2014 Elsevier Ltd. All rights reserved.

Despite the widespread observations on the osteogenic effects of magnesium ion (Mg), the diverse roles of Mg during bone healing have not been systematically dissected. Here, we reveal a previously unknown, biphasic mode of action of Mg in bone repair. During the early inflammation phase, Mg contributes to an upregulated expression of transient receptor potential cation channel member 7 (TRPM7), and a TRPM7-dependent influx of Mg in the monocyte-macrophage lineage, resulting in the cleavage and nuclear accumulation of TRPM7-cleaved kinase fragments (M7CKs). This then triggers the phosphorylation of Histone H3 at serine 10, in a TRPM7-dependent manner at the promoters of inflammatory cytokines, leading to the formation of a pro-osteogenic immune microenvironment. In the later remodeling phase, however, the continued exposure of Mg not only lead to the over-activation of NF-κB signaling in macrophages and increased number of osteoclastic-like cells but also decelerates bone maturation through the suppression of hydroxyapatite precipitation. Thus, the negative effects of Mg on osteogenesis can override the initial pro-osteogenic benefits of Mg. Taken together, this study establishes a paradigm shift in the understanding of the diverse and multifaceted roles of Mg in bone healing.