Biocompatibility Assessment of Novel Bioresorbable Alloys Mg-Zn-Se and Mg-Zn-Cu for Endovascular Applications: In Vitro Studies

Abstract:

Previous studies have shown that using biodegradable magnesium alloys such as Mg-Zn and Mg-Zn-Al possess the appropriate mechanical properties and biocompatibility to serve in a multitude of biological applications ranging from endovascular to orthopaedic and fixation devices. The objective of this study was to evaluate the biocompatibility of novel as-cast magnesium alloys Mg-1Zn-1Cu wt.% and Mg-1Zn-1Se wt.% as potential implantable biomedical materials, and compare their biologically effective properties to a binary Mg-Zn alloy. The cytotoxicity of these experimental alloys was evaluated using a tetrazolium based-MTS (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium) assay and a lactate dehydrogenase membrane integrity assay (LDH). The MTS assay was performed on extract solutions obtained from a 30-day period of alloy immersion and agitation in simulated body fluid to evaluate the major degradation products eluted from the alloy materials. Human foreskin fibroblast cell growth on the experimental magnesium alloys was evaluated for a 72 hour period, and cell death was quantified by measuring lactate dehydrogenase concentrations. Both Mg-Zn-Se and Mg-Zn-Cu alloys exhibit low cytotoxicity levels which are suitable for biomaterial applications. The Mg-Zn-Cu alloy was found to completely degrade within 72 hours, resulting in lower human foreskin fibroblast cell viability. The Mg-Zn-Se alloy was shown to be less cytotoxic than both the Mg-Zn-Cu and Mg-Zn alloys.

• Periodical: Journal of Biomimetics, Biomaterials and Tissue Engineering (Volume 17)
• Pages: 25-43
• DOI: https://doi.org/10.4028/www.scientific.net/JBBTE.17.25
• Online since: June 2013
• Authors: Dharam Persaud-Sharma, Noah Budiansky, Anthony J. McGoron
• Keywords: Biocompatibility, Biodegradable Alloys, Cell Adhesion, Cytotoxicity, Magnesium

References

[1] M. Moravej, D. Mantovani. Biodegradable metals for cardiovascular stent application: interest and new opportunities. Int. J. Mol. Sci., (2011), 12 (7), 4250-70.

DOI: 10.3390/ijms12074250

[2] E. Ma, J. Xu. Biodegradable Alloys: The glass window of opportunities. Nature Materials, (2009), 8, 855-57.

[3] H. Hermawan, D. Dubé, D. Mantovani. Degradable metallic biomaterials: design and development of Fe-Mn alloys for stents. J. Biomed. Mater. Res. A, (2010), 93(1), 1-11.

DOI: 10.1002/jbm.a.32224

[4] B. Liu, Y.F Zheng, L. Ruan. In-vitro investigation of Fe30MnSi shape memory alloy as a potential biodegradable material. Materials Letters, (2011), 65, 540-543.

DOI: 10.1016/j.matlet.2010.10.068

[5] A. Lendlein, A.T Neffe, B.F Pierce, J. Vienken. Why are so few degradable polymeric biomaterials currently established in clinical applications? Int. J. Artif. Organs, (2011), 34 (2), 71-75.

DOI: 10.5301/ijao.2011.6422

[6] D. Persaud-Sharma, A. McGoron. Biodegradable magnesium alloys: a review of material development and applications. J. Biomim., Biomater. Tiss. Eng., (2012), 12, 25-39.

DOI: 10.4028/www.scientific.net/jbbte.12.25

[7] Z.G Huan, M.A Leeflang, J. Zhou, L.E Fratila-Apachitei, J. Duszczyk. In-vitro degradation behavior and cytocompatibility of Mg-Zn-Zr alloys. J. Mater. Sci.: Mater. Med., (2010), 21 (9), 2623-35.

DOI: 10.1007/s10856-010-4111-8

[8] V.M Babkin. Effect of zirconium on the grain size of magnesium containing 4.5% Zn. Metal Sci. Heat Treat., (1963), 5 (9), 543-44.

DOI: 10.1007/bf00648969

[9] J.M Benson. Safety considerations when handling metal powders. J. South African Instit. Mining and Metallurgy, (2012), 112 (7), 563-75.

[10] M. Rederstoff, A. Krol, A. Lescure. Understanding the importance of selenium and selenoproteins in muscle function. Cell. Mol Life Sci., (2006), 63 (1), 52-9.

DOI: 10.1007/s00018-005-5313-y

[11] D.L Hartfield. Introduction to Selenium, Selenium: Its Molecular Biology and Role in Human Health. (2001). Springer, Boston.

[12] J.R Turnlund. Copper, in: M.E Shils, M. Shike, A.C Ross, B. Caballero, R.J Cousins. Modern Nutrition in Health and Disease. 10th edition. Philadelphia: Lippincott, Williams & Wilkins. (2005), 286-99.

[13] M.Angelova, S. Asenova, V. Nedkova, R. Koleva-Kolarova. Copper in the Human Organism. Trakia J. Sciences, (2011), 9 (1), 88-98.

[14] D. Persaud-Sharma, N. Budiansky, A. McGoron. Mechanical properties and tensile failure analysis of novel-bioabsorbable Mg-Zn-Cu and Mg-Zn-Se Alloys for endovascular applications. Metals, (2013), 3, 23-40.

DOI: 10.3390/met3010023

[15] L.M Gaetke, C.K Chow. Copper toxicity, oxidative stress, and antioxidant nutrients. Toxicology, (2003), 189 (1-2), 147-63.

DOI: 10.1016/s0300-483x(03)00159-8

[16] R. Alvarez, H. Martin, M.F Horstemeyer, M. Chandler, N. Williams, P. Wang, A. Ruiz. Corrosion relationship as a function of time and surface roughness on a structural AE44 Magnesium alloy. Corrosion Sci., (2010), 52 (5), 1635-48.

DOI: 10.1016/j.corsci.2010.01.018

[17] R. Walter, B. Kannan. Influence of surface roughness on the corrosion behavior of magnesium alloy. Mater. and Design, (2011), 32 (4), 2350-54.

[18] D. Persaud-Sharma, N. Munroe, A.J McGoron. Electro and magneto-electropolished surface micro-patterning on binary and ternary Nitinol. Trends Biomater. Artif. Organs, (2012), 26 (2), 74-85.

[19] P.C Hiemenz, R. Rajagopolan. Principles of Colloid and Surface Chemistry, (1997), 3rd Edition, Marcel Dekker, Inc.

[20] K. Grundke. Wetting, Spreading, and Penetration, in: Handbook of Applied Surface and Colloid Chemistry. (2002), K. Holmberg, Editor, John Wiley & Sons, Ltd.

[21] T. Young. An Essay on the Cohesion of Fluids. Philosophical Transactions of the Royal Society of London. (1805), 95, 65-87.

DOI: 10.1098/rstl.1805.0005

[22] R.N Wenzel. Resistance of Solid Surfaces to wetting by Water. Ind. Eng Chem., (1936), 28 (8), 988-94.

[23] A.B.D Cassie, S. Baxter. Wettability of Porous Surfaces. Trans. Faraday Soc., (1944), 40, 546-51.

DOI: 10.1039/tf9444000546

[24] D. Chen, Y. He, H. Tao, Y. Zhang, Y. Jiang, X. Zhang, S. Zhang. Biocompatibility of magnesium-zinc alloy in biodegradable orthopedic implants. Int. J. Mol. Med., (2011), 28 (3), 343-48.

DOI: 10.3892/ijmm.2011.707

[25] G.J Brewer. The risks of copper-toxicity contributing to cognitive decline in the aging population and to Alzheimer's disease. J. Am. Coll. Nutr., (2009), 28 (3), 238-42.

[26] A.P Marques, R.L Reis, J.A Hunt. The biocompatibility of novel starch-based polymers and composites: in-vitro studies. Biomater., (2003), 23 (6), 1471-78.

DOI: 10.1016/s0142-9612(01)00272-1

[27] I.S Berglund, H.S Brar, N. Dolgova, A.P Acharya, B.G Keselowsky, M. Sarntinoranont, M.V Manuel. Synthesis and Characterization of Mg-Ca-Sr alloys for biodegradable orthopedic implant applications. J. Biomed. Mater. Res. B Appl. Biomater., (2012), 100 (6), 1524-34.

DOI: 10.1002/jbm.b.32721

[28] M. Bornapour, N. Muja, D. Shum-Tim, M. Cerruti, M. Pekguleryuz. Biocompatibility and biodegradability of Mg-Sr alloys: The formation of Sr-substituted hydroxyapatite. Acta Biomater., (2013), 9 (2), 5319-30.

DOI: 10.1016/j.actbio.2012.07.045

[29] S. Itoh, H. Kim, O. Nakagawa, K. Ozumi, S. Lessner, H. Aoki, K. Akram, R. McKinney, M. Ushio-Fukai, T. Fukai. Novel role of antioxidant-1 (Atox1) as a copper-dependent transcription factor involved in cell proliferation. J. Biol. Chem., (2008), 283 (14), 9157-67.

DOI: 10.1074/jbc.m709463200

[30] S. Keim, J. Brunner, B. Fabry, S. Virtanen. Control of magnesium corrosion and biocompatibility with biomimetic coatings. J. Biomed. Mater. Res. B App. Biomater., (2011), 96 (1), 84-90.

DOI: 10.1002/jbm.b.31742

[31] R.E Baier, A.E Meyer, J.R Natiella, R.R Natiella, J.M Carter. Surface properties determine bioadhesive outcomes: methods and results. J. Biomed. Mater. Res., (1984), 18 (4), 337-55.

DOI: 10.1002/jbm.820180404

[32] P. van der Valk, A.W van Pelt, H.J Busscher, H.P De Jong, C.R Wildeyuur, J. Arends. Interaction of fibroblasts and polymer surfaces: relationship between surface free energy and fibroblasts spreading. J. Biomed. Mater. Res., (1983), 17: (5), 807-17.

DOI: 10.1002/jbm.820170508

[33] Y. Xin, C. Liu, X. Zhang, G. Tang, X. Tian, P. Chu. Corrosion behavior of biomedical AZ91 magnesium alloy in simulated body fluids. J. Mater. Res., (2007), 22 (7), 2004-11.

DOI: 10.1557/jmr.2007.0233

[34] M.F Morks. Magnesium phosphate treatment of steel. Materials Letters, (2004), 58 (26), 3316-19.

DOI: 10.1016/j.matlet.2004.06.027