Unique antitumor property of the Mg-Ca-Sr alloys with addition of Zn

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Abstract

In clinical practice, tumor recurrence and metastasis after orthopedic prosthesis implantation is an intensely troublesome matter. Therefore, to develop implant materials with antitumor property is extremely necessary and meaningful. Magnesium (Mg) alloys possess superb biocompatibility, mechanical property and biodegradability in orthopedic applications. However, whether they possess antitumor property had seldom been reported. In recent years, it showed that zinc (Zn) not only promote the osteogenic activity but also exhibit good antitumor property. In our present study, Zn was selected as an alloying element for the Mg-1Ca-0.5Sr alloy to develop a multifunctional material with antitumor property. We investigated the influence of the Mg-1Ca-0.5Sr-xZn (x = 0, 2, 4, 6 wt%) alloys extracts on the proliferation rate, cell apoptosis, migration and invasion of the U2OS cell line. Our results show that Zn containing Mg alloys extracts inhibit the cell proliferation by alteration the cell cycle and inducing cell apoptosis via the activation of the mitochondria pathway. The cell migration and invasion property were also suppressed by the activation of MAPK (mitogen-activated protein kinase) pathway. Our work suggests that the Mg-1Ca-0.5Sr-6Zn alloy is expected to be a promising orthopedic implant in osteosarcoma limb-salvage surgery for avoiding tumor recurrence and metastasis.

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Comparison of the mechanism of toxicity of zinc oxide and cerium oxide nanoparticles based on dissolution and oxidative stress properties.

Tian Xia, Michael Kovochich, Monty Liong … (2008)

Nanomaterials (NM) exhibit novel physicochemical properties that determine their interaction with biological substrates and processes. Three metal oxide nanoparticles that are currently being produced in high tonnage, TiO(2), ZnO, and CeO(2), were synthesized by flame spray pyrolysis process and compared in a mechanistic study to elucidate the physicochemical characteristics that determine cellular uptake, subcellular localization, and toxic effects based on a test paradigm that was originally developed for oxidative stress and cytotoxicity in RAW 264.7 and BEAS-2B cell lines. ZnO induced toxicity in both cells, leading to the generation of reactive oxygen species (ROS), oxidant injury, excitation of inflammation, and cell death. Using ICP-MS and fluorescent-labeled ZnO, it is found that ZnO dissolution could happen in culture medium and endosomes. Nondissolved ZnO nanoparticles enter caveolae in BEAS-2B but enter lysosomes in RAW 264.7 cells in which smaller particle remnants dissolve. In contrast, fluorescent-labeled CeO(2) nanoparticles were taken up intact into caveolin-1 and LAMP-1 positive endosomal compartments, respectively, in BEAS-2B and RAW 264.7 cells, without inflammation or cytotoxicity. Instead, CeO(2) suppressed ROS production and induced cellular resistance to an exogenous source of oxidative stress. Fluorescent-labeled TiO(2) was processed by the same uptake pathways as CeO(2) but did not elicit any adverse or protective effects. These results demonstrate that metal oxide nanoparticles induce a range of biological responses that vary from cytotoxic to cytoprotective and can only be properly understood by using a tiered test strategy such as we developed for oxidative stress and adapted to study other aspects of nanoparticle toxicity.

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The history of biodegradable magnesium implants: a review.

Frank Witte (2010)

Today, more than 200years after the first production of metallic magnesium by Sir Humphry Davy in 1808, biodegradable magnesium-based metal implants are currently breaking the paradigm in biomaterial science to develop only highly corrosion resistant metals. This groundbreaking approach to temporary metallic implants is one of the latest developments in biomaterials science that is being rediscovered. It is a challenging topic, and several secrets still remain that might revolutionize various biomedical implants currently in clinical use. Magnesium alloys were investigated as implant materials long ago. A very early clinical report was given in 1878 by the physician Edward C. Huse. He used magnesium wires as ligature for bleeding vessels. Magnesium alloys for clinical use were explored during the last two centuries mainly by surgeons with various clinical backgrounds, such as cardiovascular, musculoskeletal and general surgery. Nearly all patients benefited from the treatment with magnesium implants. Although most patients experienced subcutaneous gas cavities caused by rapid implant corrosion, most patients had no pain and almost no infections were observed during the postoperative follow-up. This review critically summarizes the in vitro and in vivo knowledge and experience that has been reported on the use of magnesium and its alloys to advance the field of biodegradable metals. Copyright (c) 2010 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

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The development of binary Mg-Ca alloys for use as biodegradable materials within bone.

Zijian Li, Xunan Gu, Siquan Lou … (2008)

Binary Mg-Ca alloys with various Ca contents were fabricated under different working conditions. X-ray diffraction (XRD) analysis and optical microscopy observations showed that Mg-xCa (x=1-3 wt%) alloys were composed of two phases, alpha (Mg) and Mg2Ca. The results of tensile tests and in vitro corrosion tests indicated that the mechanical properties could be adjusted by controlling the Ca content and processing treatment. The yield strength (YS), ultimate tensile strength (UTS) and elongation decreased with increasing Ca content. The UTS and elongation of as-cast Mg-1Ca alloy (71.38+/-3.01 MPa and 1.87+/-0.14%) were largely improved after hot rolling (166.7+/-3.01 MPa and 3+/-0.78%) and hot extrusion (239.63+/-7.21 MPa and 10.63+/-0.64%). The in vitro corrosion test in simulated body fluid (SBF) indicated that the microstructure and working history of Mg-xCa alloys strongly affected their corrosion behaviors. An increasing content of Mg2Ca phase led to a higher corrosion rate whereas hot rolling and hot extrusion could reduce it. The cytotoxicity evaluation using L-929 cells revealed that Mg-1Ca alloy did not induce toxicity to cells, and the viability of cells for Mg-1Ca alloy extraction medium was better than that of control. Moreover, Mg-1Ca alloy pins, with commercial pure Ti pins as control, were implanted into the left and right rabbit femoral shafts, respectively, and observed for 1, 2 and 3 months. High activity of osteoblast and osteocytes were observed around the Mg-1Ca alloy pins as shown by hematoxylin and eosin stained tissue sections. Radiographic examination revealed that the Mg-1Ca alloy pins gradually degraded in vivo within 90 days and the newly formed bone was clearly seen at month 3. Both the in vitro and in vivo corrosion suggested that a mixture of Mg(OH)2 and hydroxyapatite formed on the surface of Mg-1Ca alloy with the extension of immersion/implantation time. In addition, no significant difference (p>0.05) of serum magnesium was detected at different degradation stages. All these results revealed that Mg-1Ca alloy had the acceptable biocompatibility as a new kind of biodegradable implant material. Based on the above results, a solid alloy/liquid solution interface model was also proposed to interpret the biocorrosion process and the associated hydroxyapatite mineralization.

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Author and article information

Journal

Journal ID (nlm-ta): Sci Rep

Journal ID (iso-abbrev): Sci Rep

Title: Scientific Reports

Publisher: Nature Publishing Group

ISSN (Electronic): 2045-2322

Publication date (Electronic): 24 February 2016

Publication date Collection: 2016

Volume: 6

Electronic Location Identifier: 21736

Affiliations

[1 ]Center for Biomedical Materials and Tissue Engineering, Academy for Advanced Interdisciplinary Studies, Peking University , Beijing 100871, China

[2 ]Southern Medical University , Guangzhou 510515, China

[3 ]Department of Orthopedics, Guangdong Key Lab of Orthopedic Technology and Implant, Guangzhou General Hospital of Guangzhou Military Command , 111 Liuhua Road, Guangzhou, Guangdong 510010, China

[4 ]Department of Materials Science and Engineering, College of Engineering, Peking University , Beijing 100871, China

Author notes

[a ] yfzheng@ 123456pku.edu.cn)

[b ] gz_yqs@ 123456126.com

[*]

These authors contributed equally to this work.

Article

Publisher Item ID: srep21736

DOI: 10.1038/srep21736

PMC ID: 4764862

PubMed ID: 26907515

SO-VID: 7578d9e2-0769-4fe3-b87f-d822ba853a36

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Unique antitumor property of the Mg-Ca-Sr alloys with addition of Zn

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Most cited references 31

Comparison of the mechanism of toxicity of zinc oxide and cerium oxide nanoparticles based on dissolution and oxidative stress properties.

The history of biodegradable magnesium implants: a review.

The development of binary Mg-Ca alloys for use as biodegradable materials within bone.

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