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2021 Issue 3 (Available Online: 2021-09-28)

    EDITORIAL
    Magnesium-based biodegradable metal materials: past, present and future
    Xiaodong Guo, Qian Wang
    2021, 2(3):  175-176.  doi:10.12336/biomatertransl.2021.03.001
    Abstract ( 231 )   HTML ( 61)   PDF (187KB) ( 542 )  
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    REVIEW
    Hongtao Yang, Wenjiao Lin, Yufeng Zheng
    2021, 2(3):  177-187.  doi:10.12336/biomatertransl.2021.03.002
    The degradable features and beneficial biological functions exhibited during degradation give biodegradable metals the potential to shift the paradigm in the treatment of orthopaedic and cardiovascular diseases.
    Abstract ( 365 )   HTML ( 78)   PDF (63002KB) ( 768 )  
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    Biodegradable metals, designed to be safely degraded and absorbed by the body after fulfil the intended functions, are of particular interest in the 21st century. The marriage of advanced biodegradable metals with clinical needs have yield unprecedented possibility. Magnesium, iron, and zinc-based materials constitute the main components of temporary, implantable metallic medical devices. A burgeoning number of studies on biodegradable metals have driven the clinical translation of biodegradable metallic devices in the fields of cardiology and orthopaedics over the last decade. Their ability to degrade as well as their beneficial biological functions elicited during degradation endow this type of material with the potential to shift the paradigm in the treatment of musculoskeletal and cardiovascular diseases. This review provides an insight into the degradation mechanism of these metallic devices in specific application sites and introduces state-of-the-art translational research in the field of biodegradable metals, as well as highlighting some challenges for materials design strategies in the context of mechanical and biological compatibility.

    Ying Luo, Jue Wang, Michael Tim Yun Ong, Patrick Shu-hang Yung, Jiali Wang, Ling Qin
    2021, 2(3):  188-196.  doi:10.12336/biomatertransl.2021.03.003
    As one of the most promising next-generation orthopaedic devices, magnesium-based screws have been successfully applied around the world in increasing clinical indications to treat fractures, contributing to rapid developments in the basic and translational research of these biodegradable metal-based implants.
    Abstract ( 465 )   HTML ( 56)   PDF (375858KB) ( 1206 )  
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    Biodegradable magnesium (Mg) or its alloys are desirable materials for development into new-generation internal fixation devices or implants with high biocompatibility, adequate mechanical modulus, and osteopromotive properties, which may overcome some of the drawbacks of the existing permanent orthopaedic implants with regard to stress-shielding of bone and beam-hardening effects on radiographic images. This review summarises the current research status of Mg-based orthopaedic implants in animals and clinical trials. First, detailed information of animal studies including bone fracture repair and anterior cruciate ligament reconstruction with the use of Mg-based orthopaedic devices is introduced. Second, the repair mechanisms of the Mg-based orthopaedic implants are also reviewed. Afterwards, reports of recent clinical cases treated using Mg-based implants in orthopaedics are summarised. Finally, the challenges and the strategies of the use of Mg-based orthopaedic implants are discussed. Taken together, the collected efforts in basic research, translational work, and clinical applications of Mg-based orthopaedic implants over the last decades greatly contribute to the development of a new generation of biodegradable metals used for the design of innovative implants for better treatment of orthopaedic conditions in patients with challenging skeletal disorders or injuries.

    Xirui Jing, Qiuyue Ding, Qinxue Wu, Weijie Su, Keda Yu, Yanlin Su, Bing Ye, Qing Gao, Tingfang Sun, Xiaodong Guo
    2021, 2(3):  197-213.  doi:10.12336/biomatertransl.2021.03.004
    This review summarises the characteristics, advantages and disadvantages of magnesium (Mg)-based bone implants, the safety and osteogenic effects of Mg-based materials used in animal models, and provides possible guidance for the selection of animal models to test such materials in future.
    Abstract ( 487 )   HTML ( 60)   PDF (49069KB) ( 959 )  
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    As a new generation of medical metal materials, degradable magnesium-based materials have excellent mechanical properties and osteogenic promoting ability, making them promising materials for the treatment of refractory bone diseases. Animal models can be used to understand and evaluate the performance of materials in complex physiological environments, providing relevant data for preclinical evaluation of implants and laying the foundation for subsequent clinical studies. To date, many researchers have studied the biocompatibility, degradability and osteogenesis of magnesium-based materials, but there is a lack of review regarding the effects of magnesium-based materials in vivo. In view of the growing interest in these materials, this review briefly describes the properties of magnesium-based materials and focuses on the safety and efficacy of magnesium-based materials in vivo. Various animal models including rats, rabbits, dogs and pigs are covered to better understand and evaluate the progress and future of magnesium-based materials. This literature analysis reveals that the magnesium-based materials have good biocompatibility and osteogenic activity, thus causing no adverse reaction around the implants in vivo, and that they exhibit a beneficial effect in the process of bone repair. In addition, the degradation rate in vivo can also be improved by means of alloying and coating. These encouraging results show a promising future for the use of magnesium-based materials in musculoskeletal disorders.

    Yu Lu, Subodh Deshmukh, Ian Jones, Yu-Lung Chiu
    2021, 2(3):  214-235.  doi:10.12336/biomatertransl.2021.03.005
    Desirable biodegradable magnesium (Mg)-based orthopaedic implants can provide superior biocompatibility, good mechanical properties and appropriate biodegradation rates over the duration of implantation, which can be tailored by different smart designs and novel fabrication strategies.
    Abstract ( 656 )   HTML ( 68)   PDF (65304KB) ( 1373 )  
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    There is increasing interest in the development of bone repair materials for biomedical applications. Magnesium (Mg)-based alloys have a natural ability to biodegrade because they corrode in aqueous media; they are thus promising materials for orthopaedic device applications in that the need for a secondary surgical operation to remove the implant can be eliminated. Notably, Mg has superior biocompatibility because Mg is found in the human body in abundance. Moreover, Mg alloys have a low elastic modulus, close to that of natural bone, which limits stress shielding. However, there are still some challenges for Mg-based fracture fixation. The degradation of Mg alloys in biological fluids can be too rapid, resulting in a loss of mechanical integrity before complete healing of the bone fracture. In order to achieve an appropriate combination of bio-corrosion and mechanical performance, the microstructure needs to be tailored properly by appropriate alloy design, as well as the use of strengthening processes and manufacturing techniques. This review covers the evolution, current strategies and future perspectives of Mg-based orthopaedic implants.

    Jialin Niu, Hua Huang, Jia Pei, Zhaohui Jin, Shaokang Guan, Guangyin Yuan
    2021, 2(3):  236-247.  doi:10.12336/biomatertransl.2021.03.06
    Three key aspects should be considered when designing new biodegradable magnesium (Mg)-based alloys for vascular stents application, which are biocompatibility and biosafety, mechanical properties, and biodegradation. These three aspects mentioned are correlative, affecting and restricting each other, and are named as Triune Principle in biodegradable Mg alloy design.
    Abstract ( 410 )   HTML ( 50)   PDF (36878KB) ( 817 )  
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    Magnesium alloys are an ideal material for biodegradable vascular stents, which can be completely absorbed in the human body, and have good biosafety and mechanical properties. However, the rapid corrosion rate and excessive localized corrosion, as well as challenges in the preparation and processing of microtubes for stents, are restricting the clinical application of magnesium-based vascular stents. In the present work we will give an overview of the recent progresses on biodegradable magnesium based vascular stents including magnesium alloy design, high-precision microtubes processing, stent shape optimisation and functional coating preparation. In particular, the Triune Principle in biodegradable magnesium alloy design is proposed based on our research experience, which requires three key aspects to be considered when designing new biodegradable magnesium alloys for vascular stents application, i.e. biocompatibility and biosafety, mechanical properties, and biodegradation. This review hopes to inspire the future studies on the design and development of biodegradable magnesium alloy-based vascular stents.

    Qingchuan Wang, Weidan Wang, Yanfang Li, Weirong Li, Lili Tan, Ke Yang
    2021, 2(3):  248-256.  doi:10.12336/biomatertransl.2021.03.007
    Novel biofunctional magnesium (Mg) coatings are believed to be promising candidates for surface modification of implant materials for use in bone tissue repair. In vitro and in vivo investigations have demonstrated that Mg-coated implant materials acquire biofunctions including degradability, osteogenesis, angiogenesis and antibacterial properties.
    Abstract ( 403 )   HTML ( 56)   PDF (304378KB) ( 1190 )  
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    The lack of bioactivity of conventional medical materials leads to low osseointegration ability that may result in the occurrence of aseptic loosening in the clinic. To achieve high osseointegration, surface modifications with multiple biofunctions including degradability, osteogenesis, angiogenesis and antibacterial properties are required. However, the functions of conventional bioactive coatings are limited. Thus novel biofunctional magnesium (Mg) coatings are believed to be promising candidates for surface modification of implant materials for use in bone tissue repair. By physical vapour deposition, many previous researchers have deposited Mg coatings with high purity and granular microstructure on titanium alloys, polyetheretherketone, steels, Mg alloys and silicon. It was found that the Mg coatings with high-purity could considerably control the degradation rate in the initial stage of Mg alloy implantation, which is the most important problem for the application of Mg alloy implants. In addition, Mg coating on titanium (Ti) implant materials has been extensively studied both in vitro and in vivo, and the results indicated that their corrosion behaviour and biocompatibility are promising. Mg coatings continuously release Mg ions during the degradation process, and the alkaline environment caused by Mg degradation has obvious antibacterial effects. Meanwhile, the Mg coating has beneficial effects on osteogenesis and osseointegration, and increases the new bone-regenerating ability. Mg coatings also exhibit favourable osteogenic and angiogenic properties in vitro and increased long-term bone formation and early vascularization in vivo. Inhibitory effects of Mg coatings on osteoclasts have also been proven, which play a great role in osteoporotic patients. In addition, in order to obtain more biofunctions, other alloying elements such as copper have been added to the Mg coatings. Thus, Mg-coated Ti acquired biofunctions including degradability, osteogenesis, angiogenesis and antibacterial properties. These novel multi-functional Mg coatings are expected to significantly enhance the long-term safety of bone implants for the benefit of patients. This paper gives a brief review of studies of the microstructure, degradation behaviours and biofunctions of Mg coatings, and directions for future research are also proposed.

    Aditya Joshi, George Dias, Mark P. Staiger
    2021, 2(3):  257-271.  doi:10.12336/biomatertransl.2021.03.008
    The state-of-the-art in computational modelling of the corrosion behaviour of bioresorbable magnesium (Mg)-based implants is reviewed. Computational models have the potential to bridge the observed differences between corrosion behaviour in vitro and in vivo.
    Abstract ( 397 )   HTML ( 44)   PDF (34906KB) ( 797 )  
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    Metallic biomedical implants based on magnesium, zinc and iron alloys have emerged as bioresorbable alternatives to permanent orthopaedic implants over the last two decades. The corrosion rate of biodegradable metals plays a critical role in controlling the compatibility and functionality of the device in vivo. The broader adoption of biodegradable metals in orthopaedic applications depends on developing in vitro methods that accurately predict the biodegradation behaviour in vivo. However, the physiological environment is a highly complex corrosion environment to replicate in the laboratory, making the in vitro-to-in vivo translation of results very challenging. Accordingly, the results from in vitro corrosion tests fail to provide a complete schema of the biodegradation behaviour of the metal in vivo. In silico approach based on computer simulations aim to bridge the observed differences between experiments performed in vitro and vivo. A critical review of the state-of-the-art of computational modelling techniques for predicting the corrosion behaviour of magnesium alloy as a biodegradable metal is presented.

    RESEARCH ARTICLE
    Jing Long, Bin Teng, Wei Zhang, Long Li, Ming Zhang, Yingqi Chen, Zhenyu Yao, Xiangbo Meng, Xinluan Wang, Ling Qin, Yuxiao Lai
    2021, 2(3):  272-284.  doi:10.12336/biomatertransl.2021.03.009
    Schematic diagram showing in vivo acute systemic toxicity study of the three dimensional (3D) printed magnesium incorporated porous polymer scaffolds, including scaffold fabrication, in vitro degradation, and in vivo acute systemic toxicity assessment.

    Abstract ( 456 )   HTML ( 83)   PDF (73438KB) ( 721 )  
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    Biodegradable polymer scaffolds combined with bioactive components which accelerate osteogenesis and angiogenesis have promise for use in clinical bone defect repair. The preclinical acute toxicity evaluation is an essential assay of implantable biomaterials to assess the biosafety for accelerating clinical translation. We have successfully developed magnesium (Mg) particles and beta-tricalcium phosphate (β-TCP) for incorporation into poly(lactic-co-glycolic acid) (PLGA) porous composite scaffolds (PTM) using low-temperature rapid prototyping three-dimensional-printing technology. The PTM scaffolds have been fully evaluated and found to exhibit excellent osteogenic capacity for bone defect repair. The preclinical evaluation of acute systemic toxicities is essential and important for development of porous scaffolds to facilitate their clinical translation. In this study, acute systemic toxicity of the PTM scaffolds was evaluated in mice by intraperitoneal injection of the extract solutions of the scaffolds. PTM composite scaffolds with different Mg and β-TCP content (denoted as PT5M, PT10M, and PT15M) were extracted with different tissue culture media, including normal saline, phosphate-buffered saline, and serum-free minimum essential medium, to create the extract solutions. The evaluation was carried out following the National Standard. The acute toxicity was fully evaluated through the collection of extensive data, including serum/organs ion concentration, fluorescence staining, and in vivo median lethal dose measurement. Mg in major organs (heart, liver, and lung), and Mg ion concentrations in serum of mice, after intraperitoneal injection of the extract solutions, were measured and showed that the extract solutions of PT15M caused significant elevation of serum Mg ion concentrations, which exceeded the safety threshold and led to the death of the mice. In contrast, the extract solutions of PT5M and PT10M scaffolds did not cause the death of the injected mice. The median lethal dose of Mg ions in vivo for mice was determined for the first time in this study to be 110.66 mg/kg, and the safety level of serum magnesium toxicity in mice is 5.4 mM, while the calcium serum safety level is determined as 3.4 mM. The study was approved by the Animal Care and Use Committee of Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences (approval No. SIAT-IRB-170401-YGS-LYX-A0346) on April 5, 2017. All these results showed that the Mg ion concentration of intraperitoneally-injected extract solutions was a determinant of mouse survival, and a high Mg ion concentration (more than 240 mM) was the pivotal factor contributing to the death of the mice, while changes in pH value showed a negligible effect. The comprehensive acute systemic toxicity evaluation for PTM porous composite scaffolds in this study provided a reference to guide the design and optimization of this composite scaffold and the results demonstrated the preclinical safety of the as-fabricated PTM scaffold with appropriate Mg content, strongly supporting the official registration process of the PTM scaffold as a medical device for clinical translation.