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In vitro and in vivo degradation behavior of Mg-0.45Zn-0.45Ca(ZX00)screws for orthopedic applications

Bioactive Materials 2023年第10期28卷 132-154页

作者： Diana C.Martinez Anna Dobkowska Romy Marek Hanna Cwieka Jakub Jaroszewicz Tomasz Płocinski Crtomir Donik Heike Helmholz berengere luthringer-feyerabend Berit Zeller-Plumhoff Regine Willumeit-Romer Wojciech Swięszkowski Biomaterials Group Materials Design DivisionFaculty of Materials Science and EngineeringWarsaw University of TechnologyWołoska 14102-507WarsawPoland Department of Orthopedics and Traumatology Medical University of GrazAuenbruggerplatz 58036GrazAustria Institute of Metallic Biomaterials Helmholtz-Zentrum Hereon GmbH21502GeesthachtGermany Department of Physics and Chemistry of Materials Institute of Metals and TechnologyUniversity of Ljubljan1Lepi Pot 11SI-1000Ljubljan1Slovenia

Magnesium (Mg) alloys have become a potential material for orthopedic implants due to their unnecessary implant removal, biocompatibility, and mechanical integrity until fracture healing. This study examined the in vitro and in vivo degradation of an Mg fixation screw composed of Mg-0.45Zn-0.45Ca (ZX00, in wt.%). With ZX00 human-sized implants, in vitro immersion tests up to 28 days under physiological conditions, along with electrochemical measurements were performed for the first time. In addition, ZX00 screws were implanted in the diaphysis of sheep for 6, 12, and 24 weeks to assess the degradation and biocompatibility of the screws in vivo. Using scanning electron microscopy (SEM) coupled with energy dispersive X-ray spectroscopy (EDX), micro-computed tomography (μCT), X-ray photoelectron spectroscopy (XPS), and histology, the surface and cross-sectional morphologies of the corrosion layers formed, as well as the bone-corrosion-layer-implant interfaces, were analyzed. Our findings from in vivo testing demonstrated that ZX00 alloy promotes bone healing and the formation of new bone in direct contact with the corrosion products. In addition, the same elemental composition of corrosion products was observed for in vitro and in vivo experiments;however, their elemental distribution and thicknesses differ depending on the implant location. Our findings suggest that the corrosion resistance was microstructure-dependent. The head zone was the least corrosion-resistant, indicating that the production procedure could impact the corrosion performance of the implant. In spite of this, the formation of new bone and no adverse effects on the surrounding tissues demonstrated that the ZX00 is a suitable Mg-based alloy for temporary bone implants.

关键词： Magnesium alloys Biodegradable implants Microstructure Electron microscopy Corrosion layers

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Controlled release of hydrogen by implantation of magnesium induces P53-mediated tumor cells apoptosis

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Bioactive Materials 2022年第3期7卷 385-396页

作者： Rui Zan Hao Wang Weijie Cai Jiahua Ni berengere J.C.luthringer-feyerabend Wenhui Wang Hongzhou Peng Weiping Ji Jun Yan Jiazeng Xia Yang Song Xiaonong Zhang State Key Laboratory of Metal Matrix Composites School of Materials Science and EngineeringShanghai Jiao Tong UniversityShanghai200240China Institute of Metallic Biomaterials Department of Biological CharacterisationHelmholtz-Zentrum Geesthacht(HZG)Geesthacht21502Germany Department of General Surgery and Translational Medicine Center Wuxi No.2 People’s HospitalAffiliated Wuxi Clinical College of Nantong UniversityJiangsu214002China Orthopaedic Department Shanghai Jiao Tong University Affiliated Sixth People’s HospitalShanghai200233China Department of General Surgery Shanghai Jiao Tong University Affiliated Sixth People’s HospitalShanghai200233China Suzhou Origin Medical Technology Co.Ltd. Suzhou215513China

Hydrogen has been used to suppress tumor growth with considerable *** of hydrogen gas and oral ingestion of hydrogen-rich saline are two common systemic routes of hydrogen *** have developed a topical delivery method of hydrogen at targeted sites through the degradation of magnesium-based ***,the underlying mechanism of hydrogen’s role in cancer treatment remains ***,we investigate the mechanism of tumor cell apoptosis triggered by the hydrogen released from magnesium-based *** find that the localized release of hydrogen increases the expression level of P53 tumor suppressor proteins,as demonstrated by the in vitro RNA sequencing and protein expression ***,the P53 proteins disrupt the membrane potential of mitochondria,activate autophagy,suppress the reactive oxygen species in cancer cells,and finally result in tumor *** anti-tumor efficacy of magnesium-based biomaterials is further validated in vivo by inserting magnesium wire into the subcutaneous tumor in a *** also discovered that the minimal hydrogen concentration from magnesium wires to trigger substantial tumor apoptosis is 91.2μL/mm^(3)per day,which is much lower than that required for hydrogen *** together,these findings reveal the release of H2 from magnesium-based biomaterial exerts its anti-tumoral activity by activating the P53-mediated lysosome-mitochondria apoptosis signaling pathway,which strengthens the therapeutic potential of this biomaterial as localized anti-tumor treatment.

关键词： Biodegradable magnesium Hydrogen Tumor apoptosis Underlying mechanism P53

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Slow degrading Mg-based materials induce tumor cell dormancy on an osteosarcoma-fibroblast coculture model

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Bioactive Materials 2022年第10期7卷 320-333页

作者： Philipp Globig Regine Willumeit-Römer Fernanda Martini Elisa Mazzoni berengere J.Cluthringer-feyerabend Institute of Metallic Biomaterials Helmholtz-Zentrum Hereon21502GeesthachtGermany Department of Medical Sciences University of Ferrara44121FerraraItaly

Osteosarcoma is one of the most common cancers in young adults and is commonly treated using surgery and *** the past years,these therapy approaches improved but failed to ameliorate the ***,novel,targeted therapeutic approaches should be established to enhance treatment success while preserving patient’s quality of *** studies suggest the application of degradable magnesium(Mg)alloys as orthopedic implants bearing a potential antitumor ***,we examined the influence of Mg-based materials on an osteosarcoma-fibroblast ***,Mg and Mg-6Ag did not lead to tumor cell apoptosis at low degradation ***,the Mg-based materials induced cellular dormancy in the cancer cells indicated by a lower number of Ki-67 positive cancer cells and a higher p38 *** dormancy-like state could be reversed by reseeding on non-degrading glass slides but could not be provoked by inhibition of the protein kinase R-like endoplasmic reticulum *** investigating the influence of the disjunct surface-near effects of the Mg degradation on cell proliferation,an increased pH was found to be a main initiator of Mg degradation-dependent tumor cell proliferation inhibition.

关键词： Cancer Magnesium degradation Ki-67 Proliferation inhibition pH Alkalization

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Mg-based materials diminish tumor spreading and cancer metastases

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Bioactive Materials 2023年第1期19卷 594-610页

作者： Philipp Globig Roshani Madurawala Regine Willumeit-Römer Fernanda Martini Elisa Mazzoni Bérengère J.C.luthringer-feyerabend Institute of Metallic Biomaterials Helmholtz-Zentrum Hereon GmbH21502GeesthachtGermany Department of Medical Sciences University of Ferrara44121FerraraItaly

Cancer metastases are the most common causes of cancer-related *** formation of secondary tumors at different sites in the human body can impair multiple organ function and dramatically decrease the survival of the *** this stage,it is difficulty to treat tumor growth and spreading due to arising therapy ***,it is important to prevent cancer metastases and to increase subsequent cancer therapy *** metastases are conventionally treated with radiation or ***,these treatments elicit lots of side effects,wherefore novel local treatment approaches are currently *** studies already showed anticancer activity of specially designed degradable magnesium(Mg)alloys by reducing the cancer cell *** this work,we investigated the impact of these Mg-based materials on different steps of the metastatic cascade including cancer cell migration,invasion,and cancer-induced ***,Mg and Mg-6Ag reduced cell migration and invasion of osteosarcoma cells in coculture with ***,the Mg-based materials used in this study diminished the cancer-induced *** cells incubated with conditioned media obtained from these Mg and Mg-6Ag showed a reduced cell layer permeability,a reduced proliferation and inhibited cell *** tube formation as a last step of angiogenesis was stimulated with the presence of Mg under normoxia and diminished under hypoxia.

关键词： Cancer Osteosarcoma Magnesium degradation Cell migration Cell invasion Angiogenesis

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Corrosion behaviour and cytocompatibility of selected binary magnesium-rare earth alloys

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Journal of Magnesium and Alloys 2021年第2期9卷 581-591页

作者： Hiba Azzeddine Abdelkader Hanna Achour Dakhouche Bérengère luthringer-feyerabend Department of Physics Faculty of SciencesUniversity of Mohamed BoudiafM’silaAlgeria Inorganic Materials Laboratory Department of ChemistryFaculty of SciencesUniversity of Mohamed BoudiafM’silaAlgeria Metallic Biomaterials Institute of Material ResearchHelmholtz-Zentrum Geesthacht21502 GeesthachtGermany

The corrosion behaviour of as-cast binary Mg–0.3 Ce,Mg–1.44 Nd,Mg–0.63 Gd and Mg–0.41 Dy(wt%)alloys was investigated in DMEM+10%FBS solution using electrochemical and weight loss *** results revealed that the alloys with heavy RE elements(Gd and Dy)exhibited the lowest corrosion rate compared to the alloys with light RE elements(Ce and Nd).The cytocompatibility of the Mg–RE alloys was assessed via live/dead straining after 3 and 7 *** results show that Mg–0.63 Gd alloy is a suitable candidate for biomedical applications.

关键词： Corrosion Cytotoxicity Magnesium alloys Rare earth element Weight loss test

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Effects of proteins on magnesium degradation-static *** conditions

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Journal of Magnesium and Alloys 2023年第4期11卷 1332-1342页

作者： Ruiqing Hou Frank feyerabend Heike Helmholz Vasil M.Garamus Regine Willumeit-Römer School of Materials Science and Engineering&Henan Key Laboratory of Advanced Magnesium Alloys Zhengzhou UniversityNo.100 Science AvenueZhengzhou 450001China Institute of Metallic Biomaterials Helmholtz-Zentrum Hereon(Hereon)Max-Planck-Str.1Geesthacht 21502Germany

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

关键词： Flow Bovine serum albumin Fetal bovine serum Protein adsorption

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Proteome analysis of human mesenchymal stem cells undergoing chondrogenesis when exposed to the products of various magnesium-based materials degradation

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Bioactive Materials 2019年第1期4卷 168-188页

作者： Adela Helvia Martínez Sánchez Maryam Omidi Marcus Wurlitzer Marceline Manka Fuh Frank feyerabend Hartmut Schlüter Regine Willumeit-Römer Bérengère J.C.luthringer Division of Metallic Biomaterials Institute of Material ResearchHelmholtz-Zentrum GeesthachtMax Planck Strasse 121502GeesthachtGermany Institute of Clinical Chemistry and Laboratory Medicine Mass Spectrometric ProteomicsUniversity Medical Center Hamburg-EppendorfMartinistraße 5220246HamburgGermany

Treatment of physeal fractures(15%–30%of all paediatric fractures)remains a challenge as in approximately 10%of the cases,significant growth disturbance may *** Magnesium-based implants represent a strategy to minimize damage(i.e.,load support until bone healing without second surgery).Nevertheless,the absence of harmful effects of magnesium-implants and their degradation products on the growth plate should be ***,the proteome of human mesenchymal stem cells undergoing chondrogenesis was evaluated when exposed to the products of various Magnesium-based materials *** results of this study indicate that the materials induced regulation of proteins associated with cell chondrogenesis and cartilage formation,which should be beneficial for cartilage regeneration.

关键词： Stem cells differentiation Chondrogenesis Proteomics Magnesium biomaterial Biodegradable implant

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Effects of dynamic flow rates on degradation deposition behavior of Mg scaffold

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镁合金学报(英文) 2023年第6期11卷 2054-2060页

作者： Gaozhi Jia Meng Zhou Yicong Huang Chenxin Chen Liang Jin Qian Wu Jian Weng Fei Yu Ao Xiong Guangyin Yuan Frank feyerabend Hui Zeng Department of Bone&Joint Surgery Peking University Shenzhen HospitalShenzhen Peking University-The Hong Kong University of Science and Technology Medical CenterShenzhen Institute of Information TechnologyShenzhen 518036China National Engineering Research Center of Light Alloy Net Forming&State Key Laboratory of Metal Matrix Composite Shanghai Jiao Tong UniversityShanghai 200240China Beijing Key Laboratory of Civil Aircraft Structures and Composite Materials Beijing Aircraft Technology Research Institute of COMACBeijing 102211China College of Life Science Zhejiang Chinese Medical UniversityHangzhou 310053China Shenzhen Branch Guangdong Laboratory of Lingnan Modern AgricultureGenome Analysis Laboratory of the Ministry of Agriculture and Rural AffairsAgricultural Genomics Institute at ShenzhenChinese Academy of Agricultural SciencesShenzhen 518120China Department of Orthopaedics Peking University People’s HospitalBeijing 100044China Division of Metallic Biomaterials Institute of Materials ResearchHelmholtz-Zentrum HereonGeesthacht 21502Germany National&Local Joint Engineering Research Center of Orthopaedic Biomaterials Peking University Shenzhen HospitalShenzhen 518036China

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

关键词： Porous Mg scaffold Degradability Porosity Dynamic immersion test Degradation rate

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Deteriorated corrosion performance of micro-alloyed Mg-Zn alloy after heat treatment and mechanical processing

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Journal of Materials Science & Technology 2021年第33期92卷 214-224页

作者： Yiming Jin Carsten Blawert Hong Yang Bjorn Wiese Jan Bohlen Di Mei Min Deng Frank feyerabend Regine Willumeit Division of Metallic Biomaterials Helmholtz-Zentrum Geesthacht21502 GeesthachtGermany Southwest Technology and Engineering Research Institute 400039 ChongqingChina Magnesium Innovation Center Helmholtz-Zentrum Geesthacht21502 GeesthachtGermany State Key Laboratory of Mechanical Transmissions College of Materials Science and EngineeringChongqing UniversityChongqing400044China National Engineering Research Center for Magnesium Alloys Chongqing University400044 ChongqingChina Faculty of Engineering Christian-Albrechts-Universität zu Kiel24143 KielGermany

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

关键词： Magnesium Alloy Internetallics SEM Inclusions Corrosion

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金属注射成型生物医用Ti-22Nb合金的表面形貌和细胞相容性（英文）

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Transactions of Nonferrous Metals Society of China 2018年第7期28卷 1342-1350页

作者：赵大鹏陈钰凯常可可 Thomas EBEL Bérengère JCLUTHRIGNER-feyerabend Regine WILLUMEIT-R?MER Florian PYCZAK 湖南大学生物学院 Institute of Materials Research Helmholtz-Zentrum Geesthacht 中国科学院宁波材料技术与工程研究所

采用金属注射成型(MIM)工艺制备Ti-22Nb(质量分数,%)和商业纯钛(CP-Ti)参比样,并选取电弧熔炼后抛光的Ti-22Nb作为另一种参比样。采用激光共聚焦显微镜、扫描电子显微镜和酶联免疫检测仪检测每组样品的表面拓扑结构和细胞相容性。结果显... 详细信息

采用金属注射成型(MIM)工艺制备Ti-22Nb(质量分数,%)和商业纯钛(CP-Ti)参比样,并选取电弧熔炼后抛光的Ti-22Nb作为另一种参比样。采用激光共聚焦显微镜、扫描电子显微镜和酶联免疫检测仪检测每组样品的表面拓扑结构和细胞相容性。结果显示,MIM工艺可以得到微米级粗糙度,而且采用混合元素粉而不是单一钛粉作为原料可以获得更高的表面粗糙度和比表面积。所有测试样品都不存在细胞毒性。人原代细胞在MIM Ti-22Nb样品表面(特别是在闭孔附近)的吸附效果更好。

关键词：金属注射成型 Ti-Nb合金表面拓扑结构细胞吸附细胞增殖

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