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REVIEW
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Biodegradable magnesium alloys for orthopaedic applications

Yu Lu1 Subodh Deshmukh2 Ian Jones1 Yu-Lung Chiu1*
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1 School of Metallurgy and Materials, University of Birmingham, Birmingham, UK
2 Sandwell and West Birmingham Hospitals NHS Trust, Birmingham, UK
Submitted: 1 June 2021 | Revised: 14 July 2021 | Accepted: 16 August 2021 | Published: 28 September 2021
Copyright © 2021 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution–NonCommercial–ShareAlike 4.0 License.
Abstract

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.

Keywords
biodegradability ; magnesium alloys ; mechanical behaviour ; microstructure ; orthopaedic application
References

Below is the content of the Citations in the paper which has been de-formatted, however, the content stays consistent with the original.

1.National Bureau of Statistics. The main data of the seventh national census, National Bure...os, C. M.; Muramatsu, T.; Iqbal, J.; Zhang, Y. J.; Onuma, Y.; Garcia-Garcia, H. M.; Haude, M.; Lemos, P.
2. Lu, Y.; Deshmukh, S.; Jones, I.; Chiu, Y. Biodegradable magnesium alloys for orthopaedic  applications. Biomater Transl. 2021, 2(3), 214-235.
3. Zheng, Y. F.; Gu, X. N.; Witte, F. Biodegradable metals. Mater Sci Eng R Rep. 2014, 77, 1-34.
4. Ermanno, B. Basic Composition and Structure of Bone. In Mechanical testing of bone and the bone-implant interface, An, Y. H.; Draughn, R. A.,  eds.; CRC Press: Boca Raton, 1999; pp 3-22.
5. Suzuki, H.; He, J. Evaluation on bending properties of biomaterial  GUM Metal meshed plates for bone graft applications. In IOP Conference Series: Materials Science and Engineering, IOP Publishing:  Tianjin. 2017; Vol. 269, p 012078.
6. Augat, P.; von Rüden, C. Evolution of fracture treatment with bone  plates. Injury. 2018, 49 Suppl 1, S2-S7.
7. Nana, A. D.; Joshi, A.; Lichtman, D. M. Plating of the distal radius. J Am  Acad Orthop Surg. 2005, 13, 159-171.
8. AO Foundation. AO Foundation Surgery Reference. https:// surgeryreference.aofoundation.org/. Accessed April 13, 2021.
9. Gueorguiev, B.; Lenz, M. Why and how do locking plates fail? Injury. 2018, 49 Suppl 1, S56-S60.
10. Perren, S. M. Evolution of the internal fixation of long bone fractures. The scientific basis of biological internal fixation: choosing a new  balance between stability and biology. J Bone Joint Surg Br. 2002, 84,  1093-1110.
11. Bastias, C.; Henríquez, H.; Pellegrini, M.; Rammelt, S.; Cuchacovich,  N.; Lagos, L.; Carcuro, G. Are locking plates better than non-locking  plates for treating distal tibial fractures? Foot Ankle Surg. 2014, 20, 115- 119.
12. Hsu, K. L.; Kuan, F. C.; Chang, W. L.; Liu, Y. F.; Hong, C. K.; Yeh,  M. L.; Su, W. R. Interlocking nailing of femoral shaft fractures with  an extremely narrow medullary canal is associated with iatrogenic  fractures. Injury. 2019, 50, 2306-2311.
13. Cronier, P.; Pietu, G.; Dujardin, C.; Bigorre, N.; Ducellier, F.; Gerard,  R. The concept of locking plates. Orthop Traumatol Surg Res. 2010. doi:  10.1016/j.otsr.2010.03.008.
14. McRae, R.; Esser, M. Practical Fracture Treatment. 5th ed. Churchill  Livingstone: 2008.
15. Elias, C. N.; Lima, J. H. C.; Valiev, R.; Meyers, M. A. Biomedical  applications of titanium and its alloys. JOM. 2008, 60, 46-49.
16. ASTM F67. Standard specification for unalloyed titanium, for surgical  implant applications. 2006.
17. ASTM F138-19. Standard specification for wrought 18chromium- 14nickel-2.5molybdenum stainless steel bar and wire for surgical  implants. 2020.
18. ASTM F1537-20. Standard specification for wrought cobalt- 28chromium-6molybdenum alloys for surgical implants. 2020.
19. Disegi, J. A.; Eschbach, L. Stainless steel in bone surgery. Injury. 2000, 31 Suppl 4, 2-6.
20. Disegi, J. A. Titanium alloys for fracture fixation implants. Injury. 2000, 31 Suppl 4, 14-17.
21. Golish, S. R.; Mihalko, W. M. Principles of biomechanics and  biomaterials in orthopaedic surgery. Instr Course Lect. 2011, 60, 575-581.
22. Bayraktar, H. H.; Morgan, E. F.; Niebur, G. L.; Morris, G. E.; Wong,  E. K.; Keaveny, T. M. Comparison of the elastic and yield properties of  human femoral trabecular and cortical bone tissue. J Biomech. 2004, 37,  27-35.
23. Ryan, G.; Pandit, A.; Apatsidis, D. P. Fabrication methods of porous  metals for use in orthopaedic applications. Biomaterials. 2006, 27, 2651- 2670.
24. Vamsi Krishna, B.; Xue, W.; Bose, S.; Bandyopadhyay, A. Engineered  porous metals for implants. JOM. 2008, 60, 45-48.
25. Lhotka, C.; Szekeres, T.; Steffan, I.; Zhuber, K.; Zweymüller, K. Four- year study of cobalt and chromium blood levels in patients managed  with two different metal-on-metal total hip replacements. J Orthop Res. 2003, 21, 189-195.
26. Maehara, T.; Moritani, S.; Ikuma, H.; Shinohara, K.; Yokoyama, Y.  Difficulties in removal of the titanium locking plate in Japan. Injury. 2013, 44, 1122-1126.
27. Morgan, E. F.; Unnikrisnan, G. U.; Hussein, A. I. Bone mechanical  properties in healthy and diseased states. Annu Rev Biomed Eng. 2018, 20,
28. Friedrich, H. E.; Mordike, B. L. Magnesium technology: metallurgy, design  data, applications. Springer, Berlin, Heidelberg, 2006.
29. Schweitzer, P. E. Metallic materials: physical, mechanical, and corrosion  properties. CRC Press: 2020.
30. Staiger, M. P.; Pietak, A. M.; Huadmai, J.; Dias, G. Magnesium and its  alloys as orthopedic biomaterials: a review. Biomaterials. 2006, 27, 1728- 1734.
31. Park, J. B. Biomaterials science and engineering. Plenum Press: New  York,1984.
32. Hartwig, A. Role of magnesium in genomic stability. Mutat Res. 2001, 475, 113-121.
33. Okuma, T. Magnesium and bone strength. Nutrition. 2001, 17, 679-680.
34. Song, G.; Song, S. A possible biodegradable magnesium implant  material. Adv Eng Mater. 2007, 9, 298-302.
35. Rodríguez-Sánchez, J.; Pacha-Olivenza, M. Á.; González-Martín, M.  L. Bactericidal effect of magnesium ions over planktonic and sessile  Staphylococcus epidermidis and Escherichia coli. Mater Chem Phys. 2019, 221, 342-348.
36. Xu, L.; Yu, G.; Zhang, E.; Pan, F.; Yang, K. In vivo corrosion behavior  of Mg-Mn-Zn alloy for bone implant application. J Biomed Mater Res A.  2007, 83, 703-711.
37. Saris, N. E.; Mervaala, E.; Karppanen, H.; Khawaja, J. A.; Lewenstam,  A. Magnesium. Clin Chim Acta. 2000, 294, 1-26.
38. Gu, X.; Zheng, Y.; Cheng, Y.; Zhong, S.; Xi, T. In vitro corrosion and  biocompatibility of binary magnesium alloys. Biomaterials. 2009, 30,  484-498.
39. Witte, F.; Kaese, V.; Haferkamp, H.; Switzer, E.; Meyer-Lindenberg,  A.; Wirth, C. J.; Windhagen, H. In vivo corrosion of four magnesium  alloys and the associated bone response. Biomaterials. 2005, 26, 3557- 3563.
40. Witte, F.; Ulrich, H.; Rudert, M.; Willbold, E. Biodegradable  magnesium scaffolds: Part 1: appropriate inflammatory response. J  Biomed Mater Res A. 2007, 81, 748-756.
41. Claes, L. E. Mechanical characterization of biodegradable implants. Clin  Mater. 1992, 10, 41-46.
42. Ruedi, T. P.; Buckley, R. E.; Moran, C. G. Principles of fracture  management. 2nd ed. Thieme: 2007.
43. Chalisgaonkar, R. Insight in applications, manufacturing and corrosion  behaviour of magnesium and its alloys – A review. Mater Today Proc. 2020, 26, 1060-1071.
44. Scarritt, M. E.; Londono, R.; Badylak, S. F. Host response to implanted  materials and devices: an overview. In The immune response to implanted  materials and devices: the impact of the immune system on the success of an  implant, Corradetti, B., ed. Springer International Publishing: Cham,  2017; pp 1-14.

45. Lu, Y. Microstructure and degradation behaviour of Mg-Zn(-Ca) alloys. University of Birmingham: Birmingham,2014.
46. Song, G.; Atrens, A. Understanding magnesium corrosion—a  framework for improved alloy performance. Adv Eng Mater. 2003, 5,  837-858.
47. Ambat, R.; Aung, N. N.; Zhou, W. Studies on the influence of chloride  ion and pH on the corrosion and electrochemical behaviour of AZ91D  magnesium alloy. J Appl Electrochem. 2000, 30, 865-874.
48. Ambat, R.; Aung, N. N.; Zhou, W. Evaluation of microstructural effects  on corrosion behaviour of AZ91D magnesium alloy. Corros Sci. 2000, 42, 1433-1455.
49. Kraus, T.; Fischerauer, S. F.; Hänzi, A. C.; Uggowitzer, P. J.; Löffler,  J. F.; Weinberg, A. M. Magnesium alloys for temporary implants in  osteosynthesis: in vivo studies of their degradation and interaction with  bone. Acta Biomater. 2012, 8, 1230-1238.
50. Xin, Y.; Hu, T.; Chu, P. K. In vitro studies of biomedical magnesium  alloys in a simulated physiological environment: a review. Acta  Biomater. 2011, 7, 1452-1459.
51. Holweg, P.; Berger, L.; Cihova, M.; Donohue, N.; Clement, B.;  Schwarze, U.; Sommer, N. G.; Hohenberger, G.; van den Beucken,  J.; Seibert, F.; Leithner, A.; Löffler, J. F.; Weinberg, A. M. A  lean magnesium-zinc-calcium alloy ZX00 used for bone fracture  stabilization in a large growing-animal model. Acta Biomater. 2020, 113,  646-659.
52. Jahnen-Dechent, W.; Ketteler, M. Magnesium basics. Clin Kidney J.  2012, 5, i3-i14.
53. Shahi, A.; Aslani, S.; Ataollahi, M.; Mahmoudi, M. The role of  magnesium in different inflammatory diseases. Inflammopharmacology. 2019, 27, 649-661.
54. al-Ghamdi, S. M.; Cameron, E. C.; Sutton, R. A. Magnesium deficiency:  pathophysiologic and clinical overview. Am J Kidney Dis. 1994, 24, 737- 752.
55. Ding, S.; Zhang, J.; Tian, Y.; Huang, B.; Yuan, Y.; Liu, C. Magnesium  modification up-regulates the bioactivity of bone morphogenetic  protein-2 upon calcium phosphate cement via enhanced BMP receptor  recognition and Smad signaling pathway. Colloids Surf B Biointerfaces. 2016, 145, 140-151.
56. Zhou, H.; Liang, B.; Jiang, H.; Deng, Z.; Yu, K. Magnesium-based  biomaterials as emerging agents for bone repair and regeneration: from  mechanism to application. J Magnes Alloys. 2021, 9, 779-804.
57. Qiao, W.; Wong, K. H. M.; Shen, J.; Wang, W.; Wu, J.; Li, J.; Lin,  Z.; Chen, Z.; Matinlinna, J. P.; Zheng, Y.; Wu, S.; Liu, X.; Lai, K. P.;  Chen, Z.; Lam, Y. W.; Cheung, K. M. C.; Yeung, K. W. K. TRPM7  kinase-mediated immunomodulation in macrophage plays a central role  in magnesium ion-induced bone regeneration. Nat Commun. 2021, 12,  2885.
58. Zhang, Y.; Xu, J.; Ruan, Y. C.; Yu, M. K.; O’Laughlin, M.; Wise, H.;  Chen, D.; Tian, L.; Shi, D.; Wang, J.; Chen, S.; Feng, J. Q.; Chow, D. H.;  Xie, X.; Zheng, L.; Huang, L.; Huang, S.; Leung, K.; Lu, N.; Zhao, L.;  Li, H.; Zhao, D.; Guo, X.; Chan, K.; Witte, F.; Chan, H. C.; Zheng, Y.;  Qin, L. Implant-derived magnesium induces local neuronal production  of CGRP to improve bone-fracture healing in rats. Nat Med. 2016, 22,
59. Cheng, S.; Zhang, D.; Li, M.; Liu, X.; Zhang, Y.; Qian, S.; Peng, F.  Osteogenesis, angiogenesis and immune response of Mg-Al layered  double hydroxide coating on pure Mg. Bioact Mater. 2021, 6, 91-105.
60. Yoshizawa, S.; Brown, A.; Barchowsky, A.; Sfeir, C. Magnesium ion  stimulation of bone marrow stromal cells enhances osteogenic activity,  simulating the effect of magnesium alloy degradation. Acta Biomater. 2014, 10, 2834-2842.
61. Salimi, M. H.; Heughebaert, J. C.; Nancollas, G. H. Crystal growth of  calcium phosphates in the presence of magnesium ions. Langmuir. 1985,  1, 119-122.
62. Fox, C.; Ramsoomair, D.; Carter, C. Magnesium: its proven and  potential clinical significance. South Med J. 2001, 94, 1195-1201.
63. Musso, C. G. Magnesium metabolism in health and disease. Int Urol  Nephrol. 2009, 41, 357-362.
64. Institute of Medicine Standing Committee on the Scientific Evaluation  of Dietary Reference, I. The National Academies Collection: Reports
65. Office of Dietary Supplements, National Institutes of Health. Magnesium: fact sheet for health professionals. https://ods.od.nih.gov/ factsheets/Magnesium-HealthProfessional/. Accessed May 1, 2021.
66. Windhagen, H.; Radtke, K.; Weizbauer, A.; Diekmann, J.; Noll,  Y.; Kreimeyer, U.; Schavan, R.; Stukenborg-Colsman, C.; Waizy,  H. Biodegradable magnesium-based screw clinically equivalent to  titanium screw in hallux valgus surgery: short term results of the first  prospective, randomized, controlled clinical pilot study. Biomed Eng  Online. 2013, 12, 62.
67. Willbold, E.; Kaya, A. A.; Kaya, R. A.; Beckmann, F.; Witte, F.  Corrosion of magnesium alloy AZ31 screws is dependent on the  implantation site. Mater Sci Eng B. 2011, 176, 1835-1840.

68. Thomann, M.; Krause, C.; Bormann, D.; von der Höh, N.; Windhagen,  H.; Meyer-Lindenberg, A. Comparison of the resorbable magnesium .
69. Gilbert, S. G. A small dose of toxicology: the health effects of common  chemicals. CRC Press: 2004.
70. World Health Organization, International Atomic Energy  Agency & Food and Agriculture Organization of the United Nations. Trace elements in human nutrition and health. World Health Organization:  Geneva, 1996.
71. Alzheimer’s Society. Aluminium, metals and dementia. https://www.
72. Exley, C. The coordination chemistry of aluminium in  neurodegenerative disease. Coord Chem Rev. 2012, 256, 2142-2146.
73. Exley, C. What is the risk of aluminium as a neurotoxin? Expert Rev  Neurother. 2014, 14, 589-591.
74. Liu, X.; Shan, D.; Song, Y.; Han, E.H. Influence of yttrium element on  the corrosion behaviors of Mg–Y binary magnesium alloy. J Magnes  Alloys. 2017, 5, 26-34.
75. Miller, P. L.; Shaw, B. A.; Wendt, R. G.; Moshier, W. C. Assessing the  corrosion resistance of nonequilibrium magnesium-yttrium alloys. Corrosion. 1995, 51, 922-931.
76. McCarty, M. F. Reported antiatherosclerotic activity of silicon may
77. Pors Nielsen, S. The biological role of strontium. Bone. 2004, 35, 583- 588.
78. Atkins, G. J.; Welldon, K. J.; Halbout, P.; Findlay, D. M. Strontium  ranelate treatment of human primary osteoblasts promotes an  osteocyte-like phenotype while eliciting an osteoprotegerin response. Osteoporos Int. 2009, 20, 653-664.
79. Qin, H.; Zhao, Y.; An, Z.; Cheng, M.; Wang, Q.; Cheng, T.; Wang,  Q.; Wang, J.; Jiang, Y.; Zhang, X.; Yuan, G. Enhanced antibacterial  properties, biocompatibility, and corrosion resistance of degradable  Mg-Nd-Zn-Zr alloy. Biomaterials. 2015, 53, 211-220.
80. Alzheimer’s Society. Aluminium, metals and dementia. https://www.
81. Exley, C. The coordination chemistry of aluminium in  neurodegenerative disease. Coord Chem Rev. 2012, 256, 2142-2146.
82. Exley, C. What is the risk of aluminium as a neurotoxin? Expert Rev  Neurother. 2014, 14, 589-591.
83. CrystalMaker Software Ltd. Elements, atomic radii and the periodic  table: How big is an atom? Why does its size vary? How can we show  this in CrystalMaker? http://crystalmaker.com/support/tutorials/ atomic-radii/index.html. Accessed June 4, 2021.
84. CrystalMaker Software Ltd. Elements, atomic radii and the periodic  table: How big is an atom? Why does its size vary? How can we show  this in CrystalMaker? http://crystalmaker.com/support/tutorials/ atomic-radii/index.html. Accessed June 4, 2021.
85. CrystalMaker Software Ltd. Elements, atomic radii and the periodic  table: How big is an atom? Why does its size vary? How can we show  this in CrystalMaker? http://crystalmaker.com/support/tutorials/ atomic-radii/index.html. Accessed June 4, 2021.
86. Easton, M. A.; StJohn, D. H. A model of grain refinement incorporating  alloy constitution and potency of heterogeneous nucleant particles. Acta  Mater. 2001, 49, 1867-1878.
87. Easton, M.; StJohn, D. Grain refinement of aluminum alloys: Part I. the  nucleant and solute paradigms—a review of the literature. Metall Mater  Trans A. 1999, 30, 1613-1623.
88. Easton, M.; StJohn, D. Grain refinement of aluminum alloys: Part II.  Confirmation of, and a mechanism for, the solute paradigm. Metall  Mater Trans A. 1999, 30, 1625-1633.
89. StJohn, D. H.; Qian, M.; Easton, M. A.; Cao, P.; Hildebrand, Z. Grain  refinement of magnesium alloys. Metall Mater Trans A. 2005, 36, 1669- 1679.
90. Lee, Y. C.; Dahle, A. K.; StJohn, D. H. The role of solute in grain  refinement of magnesium. Metall Mater Trans A. 2000, 31, 2895-2906.
91. Song, G. L.; Atrens, A. Corrosion mechanisms of magnesium alloys. Adv Eng Mater. 1999, 1, 11-33.
92. Velikokhatnyi, O. I.; Kumta, P. N. First-principles studies on alloying  and simplified thermodynamic aqueous chemical stability of calcium-,  zinc-, aluminum-, yttrium- and iron-doped magnesium alloys. Acta  Biomater. 2010, 6, 1698-1704.
93. Li, H.; Wang, P.; Lin, G.; Huang, J. The role of rare earth elements in  biodegradable metals: A review. Acta Biomater. 2021, 129, 33-42.
94. Zhang, X.; Yuan, G.; Mao, L.; Niu, J.; Ding, W. Biocorrosion properties  of as-extruded Mg–Nd–Zn–Zr alloy compared with commercial AZ31  and WE43 alloys. Mater Lett. 2012, 66, 209-211.
95. Wang, L.; Li, J. B.; Li, L.; Nie, K. B.; Zhang, J. S.; Yang, C. W.; Yan, P.  W.; Liu, Y. P.; Xu, C. X. Microstructure, mechanical and bio-corrosion  properties of Mg–Zn–Zr alloys with minor Ca addition. Mater Sci  Technol. 2017, 33, 9-16.
96. Yin, D. S.; Zhang, E. L.; Zeng, S. Y. Effect of Zn on mechanical property  and corrosion property of extruded Mg-Zn-Mn alloy. Trans Nonferrous  Metals Soc China. 2008, 18, 763-768.
97. Kang, Y. H.; Wu, D.; Chen, R. S.; Han, E. H. Microstructures and  mechanical properties of the age hardened Mg–4.2Y–2.5Nd–1Gd–0.6Zr  (WE43) microalloyed with Zn. J Magnes Alloys. 2014, 2, 109-115.
98. Hänzi, A. C.; Gerber, I.; Schinhammer, M.; Löffler, J. F.; Uggowitzer, P.  J. On the in vitro and in vivo degradation performance and biological  response of new biodegradable Mg-Y-Zn alloys. Acta Biomater. 2010, 6,  1824-1833.
99. Peng, Q.; Huang, Y.; Zhou, L.; Hort, N.; Kainer, K. U. Preparation and  properties of high purity Mg-Y biomaterials. Biomaterials. 2010, 31, 398- 403.

100. Lu, Y.; Bradshaw, A. R.; Chiu, Y. L.; Jones, I. P. The role of β1’
101. Cheng, M.; Chen, J.; Yan, H.; Su, B.; Yu, Z.; Xia, W.; Gong, X. Effects
102. Lu, Y.; Chiu, Y. L.; Jones, I. P. Three-dimensional analysis of the  microstructure and bio-corrosion of Mg–Zn and Mg–Zn–Ca alloys.
103. Li, Z.; Gu, X.; Lou, S.; Zheng, Y. The development of binary Mg-Ca  alloys for use as biodegradable materials within bone. Biomaterials. 2008, 29, 1329-1344.
104. Sun, Y.; Zhang, B.; Wang, Y.; Geng, L.; Jiao, X. Preparation and
105. Lu, Y.; Ding, R. G.; Chiu, Y. L.; Jones, I. P. Tomographic investigation  of the effects of second phases on the biodegradation and nano- mechanical performance of a Mg–Zn–Ca alloy. Materialia. 2018, 4, 1-9.
106. Zhang, E.; Yang, L.; Xu, J.; Chen, H. Microstructure, mechanical  properties and bio-corrosion properties of Mg-Si(-Ca, Zn) alloy for  biomedical application. Acta Biomater. 2010, 6, 1756-1762.
107. Zhao, C.; Pan, F.; Zhang, L.; Pan, H.; Song, K.; Tang, A.
108. Wen, Z.; Wu, C.; Dai, C.; Yang, F. Corrosion behaviors of Mg and its  alloys with different Al contents in a modified simulated body fluid. J  Alloys Compd. 2009, 488, 392-399.
109. Witte, F.; Fischer, J.; Nellesen, J.; Crostack, H. A.; Kaese, V.; Pisch,  A.; Beckmann, F.; Windhagen, H. In vitro and in vivo corrosion  measurements of magnesium alloys. Biomaterials. 2006, 27, 1013-1018.
110. Zhang, B.; Hou, Y.; Wang, X.; Wang, Y.; Geng, L. Mechanical
111. Lu, Y.; Bradshaw, A. R.; Chiu, Y. L.; Jones, I. P. Effects of secondary  phase and grain size on the corrosion of biodegradable Mg-Zn-Ca  alloys. Mater Sci Eng C Mater Biol Appl. 2015, 48, 480-486.
112. Cho, D. H.; Lee, B. W.; Park, J. Y.; Cho, K. M.; Park, I. M. Effect of Mn  addition on corrosion properties of biodegradable Mg-4Zn-0.5Ca-xMn  alloys. J Alloys Compd. 2017, 695, 1166-1174.
113. Zhang, E.; He, W.; Du, H.; Yang, K. Microstructure, mechanical
114. Zhang, X.; Wu, Y.; Xue, Y.; Wang, Z.; Yang, L. Biocorrosion behavior  and cytotoxicity of a Mg–Gd–Zn–Zr alloy with long period stacking  ordered structure. Mater Lett. 2012, 86, 42-45.
115. Krause, A.; von der Höh, N.; Bormann, D.; Krause, C.; Bach, F. W.;  Windhagen, H.; Meyer-Lindenberg, A. Degradation behaviour and  mechanical properties of magnesium implants in rabbit tibiae. J Mater  Sci. 2010, 45, 624-632.
116. Gu, X. N.; Xie, X. H.; Li, N.; Zheng, Y. F.; Qin, L. In vitro and in vivo  studies on a Mg-Sr binary alloy system developed as a new kind of  biodegradable metal. Acta Biomater. 2012, 8, 2360-2374.
117. Zhang, S.; Zhang, X.; Zhao, C.; Li, J.; Song, Y.; Xie, C.; Tao, H.;
118. Li, N.; Zheng, Y. Novel magnesium alloys developed for biomedical  application: a review. J Mater Sci Technol. 2013, 29, 489-502.
119. Song, G.; Atrens, A.; Dargusch, M. Influence of microstructure on the  corrosion of diecast AZ91D. Corros Sci. 1998, 41, 249-273.

120. Aung, N. N.; Zhou, W. Effect of grain size and twins on corrosion behaviour of AZ31B magnesium alloy. Corros Sci. 2010, 52, 589-594.  
121. Hamu, G. B.; Eliezer, D.; Wagner, L. The relation between severe plastic deformation microstructure and corrosion behavior of AZ31 magnesium alloy. J Alloys Compd. 2009, 468, 222-229.  
122. Birbilis, N.; Ralston, K. D.; Virtanen, S.; Fraser, H. L.; Davies, C. H. J. Grain character influences on corrosion of ECAPed pure magnesium. Corros Eng Sci Technol. 2010, 45, 224-230.  
123. Ralston, K. D.; Birbilis, N.; Davies, C. H. J. Revealing the relationship between grain size and corrosion rate of metals. Scripta Mater. 2010, 63, 1201-1204.  
124. op’t Hoog, C.; Birbilis, N.; Estrin, Y. Corrosion of pure Mg as a function of grain size and processing route. Adv Eng Mater. 2008, 10, 579-582.  
125. Jang, Y. H.; Kim, S. S.; Yim, C. D.; Lee, C. G.; Kim, S. J. Corrosion behaviour of friction stir welded AZ31B Mg in 3•5%NaCl solution. Corros Eng Sci Technol. 2007, 42, 119-122.  
126. Song, G.; StJohn, D. The effect of zirconium grain refinement on the corrosion behaviour of magnesium-rare earth alloy MEZ. J Light Metals. 2002, 2, 1-16.  
127. Song, G. Recent progress in corrosion and protection of magnesium alloys. Adv Eng Mater. 2005, 7, 563-586.  
128. Lunder, O.; Lein, J. E.; Aune, T. K.; Nisancioglu, K. The role of Mg17Al12 phase in the corrosion of Mg alloy AZ91. Corrosion. 1989, 45, 741-748.  
129. Beldjoudi, T.; Fiaud, C.; Robbiola, L. Influence of homogenization and artificial aging heat treatments on corrosion behavior of Mg-Al alloys. Corrosion. 1993, 49, 738-745.  
130. Pardo, A.; Merino, M. C.; Coy, A. E.; Arrabal, R.; Viejo, F.; Matykina, E. Corrosion behaviour of magnesium/aluminium alloys in 3.5wt.% NaCl. Corros Sci. 2008, 50, 823-834.  
131. Lunder, O.; Videm, M.; Nisancioglu, K. Corrosion resistant magnesium alloys. SAE Trans. 1995, 104, 352-357.  
132. Srinivasan, A.; Ningshen, S.; Kamachi Mudali, U.; Pillai, U. T. S.; Pai, B. C. Influence of Si and Sb additions on the corrosion behavior of AZ91 magnesium alloy. Intermetallics. 2007, 15, 1511-1517.  
133. Mao, L.; Shen, L.; Chen, J.; Zhang, X.; Kwak, M.; Wu, Y.; Fan, R.; Zhang, L.; Pei, J.; Yuan, G.; Song, C.; Ge, J.; Ding, W. A promising biodegradable magnesium alloy suitable for clinical vascular stent application. Sci Rep. 2017, 7, 46343.  
134. Zhang, X.; Yuan, G.; Mao, L.; Niu, J.; Fu, P.; Ding, W. Effects of extrusion and heat treatment on the mechanical properties and biocorrosion behaviors of a Mg-Nd-Zn-Zr alloy. J Mech Behav Biomed Mater. 2012, 7, 77-86.  
135. Zong, Y.; Yuan, G.; Zhang, X.; Mao, L.; Niu, J.; Ding, W. Comparison of biodegradable behaviors of AZ31 and Mg–Nd–Zn–Zr alloys in Hank’s physiological solution. Mater Sci Eng B. 2012, 177, 395-401.  
136. Andrei, M.; Eliezer, A.; Bonora, P. L.; Gutman, E. M. DC and AC polarisation study on magnesium alloys Influence of the mechanical deformation. Mater Corros. 2002, 53, 455-461.  
137. Xin, R. L.; Wang, M. Y.; Gao, J. C.; Liu, P.; Liu, Q. Effect of microstructure and texture on corrosion resistance of magnesium alloy. Mater Sci Forum. 2009, 610-613, 1160-1163.  
138. Schmutz, P.; Guillaumin, V.; Lillard, R. S.; Lillard, J. A.; Frankel, G. S. Influence of dichromate ions on corrosion processes on pure magnesium. J Electrochem Soc. 2003, 150, B99.  
139. Gu, X.; Zheng, Y.; Zhong, S.; Xi, T.; Wang, J.; Wang, W. Corrosion of, and cellular responses to Mg-Zn-Ca bulk metallic glasses. Biomaterials. 2010, 31, 1093-1103.  
140. Zberg, B.; Uggowitzer, P. J.; Löffler, J. F. MgZnCa glasses without clinically observable hydrogen evolution for biodegradable implants. Nat Mater. 2009, 8, 887-891.  
141. Zhang, X. L.; Chen, G.; Bauer, T. Mg-based bulk metallic glass composite with high bio-corrosion resistance and excellent mechanical properties. Intermetallics. 2012, 29, 56-60.  
142. Zberg, B.; Arata, E. R.; Uggowitzer, P. J.; Löffler, J. F. Tensile properties of glassy MgZnCa wires and reliability analysis using Weibull statistics. Acta Mater. 2009, 57, 3223-3231.  
143. Park, E. S.; Kim, W. T.; Kim, D. H. Bulk glass formation in Mg-Cu-Ag-Y-Gd alloy. Mater Trans. 2004, 45, 2474-2477.  
144. Sun, Y.; Zhang, H. F.; Fu, H. M.; Wang, A. M.; Hu, Z. Q. Mg–Cu–Ag–Er bulk metallic glasses with high glass forming ability and compressive strength. Mater Sci Eng A. 2009, 502, 148-152.  
145. Wessels, V.; Le Mené, G.; Fischerauer, S. F.; Kraus, T.; Weinberg, A. M.; Uggowitzer, P. J.; Löffler, J. F. In vivo performance and structural relaxation of biodegradable bone implants made from Mg Zn Ca bulk metallic glasses. Adv Eng Mater. 2012, 14, B357-B364.  
146. Yu, H. J.; Wang, J. Q.; Shi, X. T.; Louzguine-Luzgin, D. V.; Wu, H.-K.; Perepezko, J. H. Ductile biodegradable Mg-based metallic glasses with excellent biocompatibility. Adv Funct Mater. 2013, 23, 4793-4800.  
147. Ashby, M. F.; Greer, A. L. Metallic glasses as structural materials. Scripta Mater. 2006, 54, 321-326.  
148. Razavi, M.; Fathi, M. H.; Meratian, M. Microstructure, mechanical properties and bio-corrosion evaluation of biodegradable AZ91-FA nanocomposites for biomedical applications. Mater Sci Eng A. 2010, 527, 6938-6944.  
149. Lei, T.; Tang, W.; Cai, S. H.; Feng, F. F.; Li, N. F. On the corrosion behaviour of newly developed biodegradable Mg-based metal matrix composites produced by in situ reaction. Corros Sci. 2012, 54, 270-277.  
150. Feng, A.; Han, Y. The microstructure, mechanical and corrosion properties of calcium polyphosphate reinforced ZK60A magnesium alloy composites. J Alloys Compd. 2010, 504, 585-593.  
151. Gu, X.; Zhou, W.; Zheng, Y.; Dong, L.; Xi, Y.; Chai, D. Microstructure, mechanical property, bio-corrosion and cytotoxicity evaluations of Mg/HA composites. Mater Sci Eng C. 2010, 30, 827-832.  
152. Ye, X.; Chen, M.; Yang, M.; Wei, J.; Liu, D. In vitro corrosion resistance and cytocompatibility of nano-hydroxyapatite reinforced Mg–Zn–Zr composites. J Mater Sci Mater Med. 2010, 21, 1321-1328.  
153. Liu, D.; Zuo, Y.; Meng, W.; Chen, M.; Fan, Z. Fabrication of biodegradable nano-sized β-TCP/Mg composite by a novel melt shearing technology. Mater Sci Eng C. 2012, 32, 1253-1258.  
154. Wang, T.; Lin, C.; Batalu, D.; Zhang, L.; Hu, J.; Lu, W. In vitro study of the PLLA-Mg65Zn30Ca5 composites as potential biodegradable materials for bone implants. J Magnes Alloys. 2021. doi:10.1016/j.jma.2020.12.014.  
155. Antoniac, I. V.; Antoniac, A.; Vasile, E.; Tecu, C.; Fosca, M.; Yankova, V. G.; Rau, J. V. In vitro characterization of novel nanostructured collagen-hydroxyapatite composite scaffolds doped with magnesium with improved biodegradation rate for hard tissue regeneration. Bioact Mater. 2021, 6, 3383-3395.  
156. Shen, J.; Chen, B.; Zhai, X.; Qiao, W.; Wu, S.; Liu, X.; Zhao, Y.; Ruan, C.; Pan, H.; Chu, P. K.; Cheung, K. M. C.; Yeung, K. W. K. Stepwise 3D-spatio-temporal magnesium cationic niche: Nanocomposite scaffold mediated microenvironment for modulating intramembranous ossification. Bioact Mater. 2021, 6, 503-519.  
157. Shen, J.; Wang, W.; Zhai, X.; Chen, B.; Qiao, W.; Li, W.; Li, P.; Zhao, Y.; Meng, Y.; Qian, S.; Liu, X.; Chu, P. K.; Yeung, K. W. K. 3D-printed nanocomposite scaffolds with tunable magnesium ionic microenvironment induce in situ bone tissue regeneration. Appl Mater Today. 2019, 16, 493-507.  
158. Wang, X.; Xu, S.; Zhou, S.; Xu, W.; Leary, M.; Choong, P.; Qian, M.; Brandt, M.; Xie, Y. M. Topological design and additive manufacturing of porous metals for bone scaffolds and orthopaedic implants: A review. Biomaterials. 2016, 83, 127-141.  
159. Zou, X.; Li, H.; Bünger, M.; Egund, N.; Lind, M.; Bünger, C. Bone ingrowth characteristics of porous tantalum and carbon fiber interbody devices: an experimental study in pigs. Spine J. 2004, 4, 99-105.  
160. Pamula, E.; Bacakova, L.; Filova, E.; Buczynska, J.; Dobrzynski, P.; Noskova, L.; Grausova, L. The influence of pore size on colonization of poly(L-lactide-glycolide) scaffolds with human osteoblast-like MG 63 cells in vitro. J Mater Sci Mater Med. 2008, 19, 425-435.  
161. Pamula, E.; Filová, E.; Bacáková, L.; Lisá, V.; Adamczyk, D. Resorbable polymeric scaffolds for bone tissue engineering: the influence of their microstructure on the growth of human osteoblast-like MG 63 cells. J Biomed Mater Res A. 2009, 89, 432-443.  
162. Lefebvre, L. P.; Banhart, J.; Dunand, D. C. Porous metals and metallic foams: current status and recent developments. Adv Eng Mater. 2008, 10, 775-787.  
163. Cheng, M. Q.; Wahafu, T.; Jiang, G. F.; Liu, W.; Qiao, Y. Q.; Peng, X. C.; Cheng, T.; Zhang, X. L.; He, G.; Liu, X. Y. A novel open-porous magnesium scaffold with controllable microstructures and properties for bone regeneration. Sci Rep. 2016, 6, 24134.  
164. Razavi, M.; Fathi, M.; Savabi, O.; Vashaee, D.; Tayebi, L. In vitro study of nanostructured diopside coating on Mg alloy orthopedic implants. Mater Sci Eng C Mater Biol Appl. 2014, 41, 168-177.  
165. Li, Y.; Zhou, J.; Pavanram, P.; Leeflang, M. A.; Fockaert, L. I.; Pouran, B.; Tümer, N.; Schröder, K. U.; Mol, J. M. C.; Weinans, H.; Jahr, H.; Zadpoor, A. A. Additively manufactured biodegradable porous magnesium. Acta Biomater. 2018, 67, 378-392.  
166. Geng, F.; Tan, L.; Zhang, B.; Wu, C.; He, Y.; Yang, J.; Yang, K. Study on β-TCP coated porous Mg as a bone tissue engineering scaffold material. J Mater Sci Technol. 2009, 25, 123-129.  
167. Tan, L.; Gong, M.; Zheng, F.; Zhang, B.; Yang, K. Study on compression behavior of porous magnesium used as bone tissue engineering scaffolds. Biomed Mater. 2009, 4, 015016.  
168. Witte, F.; Ulrich, H.; Palm, C.; Willbold, E. Biodegradable magnesium scaffolds: Part II: peri-implant bone remodeling. J Biomed Mater Res A. 2007, 81, 757-765.  
169. Gu, X. N.; Zhou, W. R.; Zheng, Y. F.; Liu, Y.; Li, Y. X. Degradation and cytotoxicity of lotus-type porous pure magnesium as potential tissue engineering scaffold material. Mater Lett. 2010, 64, 1871-1874.  
170. Badekila, A. K.; Kini, S.; Jaiswal, A. K. Fabrication techniques of biomimetic scaffolds in three-dimensional cell culture: A review. J Cell Physiol. 2021, 236, 741-762.  
171. Zhao, D.; Witte, F.; Lu, F.; Wang, J.; Li, J.; Qin, L. Current status on clinical applications of magnesium-based orthopaedic implants: A review from clinical translational perspective. Biomaterials. 2017, 112, 287-302.  
172. ASTM B557. Standard test methods for tension testing wrought and cast aluminum- and magnesium-alloy products. 2015.  
173. International Organization of Standards. ISO 6892-1: Metallic materials-Tensile testing-Part 1: Method of test at room temperature. 2019.  
174. ASTM WK61103. New guide for corrosion fatigue evaluation of absorbable metals. 2017.  
175. Jalota, S.; Bhaduri, S. B.; Tas, A. C. Using a synthetic body fluid (SBF) solution of 27 mM HCO3− to make bone substitutes more osteointegrative. Mater Sci Eng C. 2008, 28, 129-140.  
176. Zhang, X.; Yuan, G.; Niu, J.; Fu, P.; Ding, W. Microstructure, mechanical properties, biocorrosion behavior, and cytotoxicity of as-extruded Mg-Nd-Zn-Zr alloy with different extrusion ratios. J Mech Behav Biomed Mater. 2012, 9, 153-162.  

177. Wang, H.; Estrin, Y.; Fu, H.; Song, G.; Zúberová, Z. The Effect of pre-processing and grain structure on the bio-corrosion and fatigue resistance of magnesium alloy AZ31. Adv Eng Mater. 2007, 9, 967-972.  
178. Witte, F.; Feyerabend, F.; Maier, P.; Fischer, J.; Störmer, M.; Blawert, C.; Dietzel, W.; Hort, N. Biodegradable magnesium-hydroxyapatite metal matrix composites. Biomaterials. 2007, 28, 2163-2174.  
179. Wang, Y.; Wei, M.; Gao, J. Improve corrosion resistance of magnesium in simulated body fluid by dicalcium phosphate dihydrate coating. Mater Sci Eng C. 2009, 29, 1311-1316.  
180. Kirkland, N. T.; Lespagnol, J.; Birbilis, N.; Staiger, M. P. A survey of bio-corrosion rates of magnesium alloys. Corros Sci. 2010, 52, 287-291.  
181. Hort, N.; Huang, Y.; Fechner, D.; Störmer, M.; Blawert, C.; Witte, F.; Vogt, C.; Drücker, H.; Willumeit, R.; Kainer, K. U.; Feyerabend, F. Magnesium alloys as implant materials--principles of property design for Mg-RE alloys. Acta Biomater. 2010, 6, 1714-1725.  
182. Song, G. L.; Atrens, A.; St.John, D. H. Magnesium technology. New Orleans, 2001.  
183. Alvarez-Lopez, M.; Pereda, M. D.; del Valle, J. A.; Fernandez-Lorenzo, M.; Garcia-Alonso, M. C.; Ruano, O. A.; Escudero, M. L. Corrosion behaviour of AZ31 magnesium alloy with different grain sizes in simulated biological fluids. Acta Biomater. 2010, 6, 1763-1771.  
184. He, W.; Zhang, E.; Yang, K. Effect of Y on the bio-corrosion behavior of extruded Mg–Zn–Mn alloy in Hank’s solution. Mater Sci Eng C. 2010, 30, 167-174.  
185. Kannan, M. B. Influence of microstructure on the in-vitro degradation behaviour of magnesium alloys. Mater Lett. 2010, 64, 739-742.  
186. Kirkland, N. T.; Birbilis, N.; Staiger, M. P. Assessing the corrosion of biodegradable magnesium implants: a critical review of current methodologies and their limitations. Acta Biomater. 2012, 8, 925-936.  
187. Song, G.; Atrens, A.; Wu, X.; Zhang, B. Corrosion behaviour of AZ21, AZ501 and AZ91 in sodium chloride. Corros Sci. 1998, 40, 1769-1791.  
188. Parai, R.; Bandyopadhyay-Ghosh, S. Engineered bio-nanocomposite magnesium scaffold for bone tissue regeneration. J Mech Behav Biomed Mater. 2019, 96, 45-52.  
189. Dutta, S.; Devi, K. B.; Gupta, S.; Kundu, B.; Balla, V. K.; Roy, M. Mechanical and in vitro degradation behavior of magnesium-bioactive glass composites prepared by SPS for biomedical applications. J Biomed Mater Res B Appl Biomater. 2019, 107, 352-365.  
190. Chen, K.; Xie, X.; Tang, H.; Sun, H.; Qin, L.; Zheng, Y.; Gu, X.; Fan, Y. In vitro and in vivo degradation behavior of Mg-2Sr-Ca and Mg-2Sr-Zn alloys. Bioact Mater. 2020, 5, 275-285.  
191. Heublein, B.; Rohde, R.; Kaese, V.; Niemeyer, M.; Hartung, W.; Haverich, A. Biocorrosion of magnesium alloys: a new principle in cardiovascular implant technology? Heart. 2003, 89, 651-656.  
192. Kaya, R. A.; Cavuşoğlu, H.; Tanik, C.; Kaya, A. A.; Duygulu, O.; Mutlu, Z.; Zengin, E.; Aydin, Y. The effects of magnesium particles in posterolateral spinal fusion: an experimental in vivo study in a sheep model. J Neurosurg Spine. 2007, 6, 141-149.  
193. Huang, S.; Wang, B.; Zhang, X.; Lu, F.; Wang, Z.; Tian, S.; Li, D.; Yang, J.; Cao, F.; Cheng, L.; Gao, Z.; Li, Y.; Qin, K.; Zhao, D. High-purity weight-bearing magnesium screw: Translational application in the healing of femoral neck fracture. Biomaterials. 2020, 238, 119829.  
194. Grün, N. G.; Holweg, P.; Tangl, S.; Eichler, J.; Berger, L.; van den Beucken, J.; Löffler, J. F.; Klestil, T.; Weinberg, A. M. Comparison of a resorbable magnesium implant in small and large growing-animal models. Acta Biomater. 2018, 78, 378-386.  
195. Huang, Q.; Liu, L.; Wu, H.; Li, K.; Li, N.; Liu, Y. The design, development, and in vivo performance of intestinal anastomosis ring fabricated by magnesium-zinc-strontium alloy. Mater Sci Eng C Mater Biol Appl. 2020, 106, 110158.  
196. Imwinkelried, T.; Beck, S.; Schaller, B. Pre-clinical testing of human size magnesium implants in miniature pigs: Implant degradation and bone fracture healing at multiple implantation sites. Mater Sci Eng C Mater Biol Appl. 2020, 108, 110389.  

197. Li, W.; Zhou, J.; Xu, Y. Study of the in vitro cytotoxicity testing of medical devices. Biomed Rep. 2015, 3, 617-620.  
198. International Organization of Standards. ISO 10993-5: biological evaluation of medical devices: tests for in vitro cytotoxicity.  
199. De Melo, W. M.; Maximiano, W. M.; Antunes, A. A.; Beloti, M. M.; Rosa, A. L.; de Oliveira, P. T. Cytotoxicity testing of methyl and ethyl 2-cyanoacrylate using direct contact assay on osteoblast cell cultures. J Oral Maxillofac Surg. 2013, 71, 35-41.  
200. Sjögren, G.; Sletten, G.; Dahl, J. E. Cytotoxicity of dental alloys, metals, and ceramics assessed by millipore filter, agar overlay, and MTT tests. J Prosthet Dent. 2000, 84, 229-236.  
201. Jin, C. Y.; Zhu, B. S.; Wang, X. F.; Lu, Q. H. Cytotoxicity of titanium dioxide nanoparticles in mouse fibroblast cells. Chem Res Toxicol. 2008, 21, 1871-1877.  
202. Liu, L.; Huang, B.; Liu, X.; Yuan, W.; Zheng, Y.; Li, Z.; Yeung, K. W. K.; Zhu, S.; Liang, Y.; Cui, Z.; Wu, S. Photo-controlled degradation of PLGA/Ti(3)C(2) hybrid coating on Mg-Sr alloy using near infrared light. Bioact Mater. 2021, 6, 568-578.  
203. Han, D.; Li, Y.; Liu, X.; Yeung, K. W. K.; Zheng, Y.; Cui, Z.; Liang, Y.; Li, Z.; Zhu, S.; Wang, X.; Wu, S. Photothermy-strengthened photocatalytic activity of polydopamine-modified metal-organic frameworks for rapid therapy of bacteria-infected wounds. J Mater Sci Technol. 2021, 62, 83-95.  
204. Sarkar, K.; Rahaman, M.; Agarwal, S.; Bodhak, S.; Halder, S.; Nandi, S. K.; Roy, M. Degradability and in vivo biocompatibility of doped magnesium phosphate bioceramic scaffolds. Mater Lett. 2020, 259, 126892.  
205. Kumar, V.; Sarkar, K.; Bavya Devi, K.; Ghosh, D.; Nandi, S. K.; Roy, M. Quantitative assessment of degradation, cytocompatibility, and in vivo bone regeneration of silicon-incorporated magnesium phosphate bioceramics. J Mater Res. 2019, 34, 4024-4036.  
206. Wang, J.; Cui, L.; Ren, Y.; Zou, Y.; Ma, J.; Wang, C.; Zheng, Z.; Chen, X.; Zeng, R.; Zheng, Y. In vitro and in vivo biodegradation and biocompatibility of an MMT/BSA composite coating upon magnesium alloy AZ31. J Mater Sci Technol. 2020, 47, 52-67.  
207. Lin, Z.; Zhao, Y.; Chu, P. K.; Wang, L.; Pan, H.; Zheng, Y.; Wu, S.; Liu, X.; Cheung, K. M. C.; Wong, T.; Yeung, K. W. K. A functionalized TiO(2)/Mg(2)TiO(4) nano-layer on biodegradable magnesium implant enables superior bone-implant integration and bacterial disinfection. Biomaterials. 2019, 219, 119372.  
208. Makkar, P.; Kang, H. J.; Padalhin, A. R.; Faruq, O.; Lee, B. In-vitro and in-vivo evaluation of strontium doped calcium phosphate coatings on biodegradable magnesium alloy for bone applications. Appl Surf Sci. 2020, 510, 145333.  
209. International Organization of Standards. ISO 10993-12: biological evaluation of medical devices: sample preparation and reference materials.  
210. Yamamoto, A.; Hiromoto, S. Effect of inorganic salts, amino acids and proteins on the degradation of pure magnesium in vitro. Mater Sci Eng C. 2009, 29, 1559-1568.  
211. Fischer, J.; Pröfrock, D.; Hort, N.; Willumeit, R.; Feyerabend, F. Improved cytotoxicity testing of magnesium materials. Mater Sci Eng B. 2011, 176, 830-834.  
212. Wang, J.; Witte, F.; Xi, T.; Zheng, Y.; Yang, K.; Yang, Y.; Zhao, D.; Meng, J.; Li, Y.; Li, W.; Chan, K.; Qin, L. Recommendation for modifying current cytotoxicity testing standards for biodegradable magnesium-based materials. Acta Biomater. 2015, 21, 237-249.  
213. Jablonská, E.; Kubásek, J.; Vojtěch, D.; Ruml, T.; Lipov, J. Test conditions can significantly affect the results of in vitro cytotoxicity testing of degradable metallic biomaterials. Sci Rep. 2021, 11, 6628.  
214. Razavi, M.; Fathi, M.; Savabi, O.; Razavi, S. M.; Heidari, F.; Manshaei, M.; Vashaee, D.; Tayebi, L. In vivo study of nanostructured diopside (CaMgSi2O6) coating on magnesium alloy as biodegradable orthopedic implants. Appl Surf Sci. 2014, 313, 60-66.  
215. Mahamood, R. M.; Akinlabi, E. T. Types of functionally graded materials and their areas of application. In Functionally Graded Materials, Mahamood, R. M.; Akinlabi, E. T., eds.; Springer International Publishing: Cham, 2017; pp 9-21.  
216. Shuai, C.; Cheng, Y.; Yang, Y.; Peng, S.; Yang, W.; Qi, F. Laser additive manufacturing of Zn-2Al part for bone repair: Formability, microstructure and properties. J Alloys Compd. 2019, 798, 606-615.  
217. Ilich, J. Z.; Kerstetter, J. E. Nutrition in bone health revisited: a story beyond calcium. J Am Coll Nutr. 2000, 19, 715-737.  
218. Atkins, G. J.; Welldon, K. J.; Halbout, P.; Findlay, D. M. Strontium ranelate treatment of human primary osteoblasts promotes an osteocyte-like phenotype while eliciting an osteoprotegerin response. Osteoporos Int. 2009, 20, 653-664.  
219. Qin, H.; Zhao, Y.; An, Z.; Cheng, M.; Wang, Q.; Cheng, T.; Wang, Q.; Wang, J.; Jiang, Y.; Zhang, X.; Yuan, G. Enhanced antibacterial properties, biocompatibility, and corrosion resistance of degradable Mg-Nd-Zn-Zr alloy. Biomaterials. 2015, 53, 211-220.  
220. Medical Devices Business Services, I. 3.5mm, 4.5mm Locking Compression Plate (LCP®). https://www.jnjmedicaldevices.com/en-US/product/35mm-45mm-locking-compression-plate-lcpr. Accessed May 10, 2021.  
221. Buzolin, R. H.; Mohedano, M.; Mendis, C. L.; Mingo, B.; Tolnai, D.; Blawert, C.; Kainer, K. U.; Pinto, H.; Hort, N. As cast microstructures on the mechanical and corrosion behaviour of ZK40 modified with Gd and Nd additions. Mater Sci Eng A. 2017, 682, 238-247.  
222. Zhao, X.; Shi, L. L.; Xu, J. A Comparison of corrosion behavior in saline environment: rare earth metals (Y, Nd, Gd, Dy) for alloying of biodegradable magnesium alloys. J Mater Sci Technol. 2013, 29, 781-787.  
223. Li, Y.; Jahr, H.; Zhang, X. Y.; Leeflang, M. A.; Li, W.; Pouran, B.; Tichelaar, F. D.; Weinans, H.; Zhou, J.; Zadpoor, A. A. Biodegradation-affected fatigue behavior of additively manufactured porous magnesium. Addit Manuf. 2019, 28, 299-311.  
224. Wei, K.; Gao, M.; Wang, Z.; Zeng, X. Effect of energy input on formability, microstructure and mechanical properties of selective laser melted AZ91D magnesium alloy. Mater Sci Eng A. 2014, 611, 212-222.  
225. Zhang, B.; Liao, H.; Coddet, C. Effects of processing parameters on properties of selective laser melting Mg–9%Al powder mixture. Mater Des. 2012, 34, 753-758.  
226. Shuai, C.; Yang, Y.; Wu, P.; Lin, X.; Liu, Y.; Zhou, Y.; Feng, P.; Liu, X.; Peng, S. Laser rapid solidification improves corrosion behavior of Mg-Zn-Zr alloy. J Alloys Compd. 2017, 691, 961-969.  
227. Wei, K.; Wang, Z.; Zeng, X. Influence of element vaporization on formability, composition, microstructure, and mechanical performance of the selective laser melted Mg–Zn–Zr components. Mater Lett. 2015, 156, 187-190.  
228. Salehi, M.; Maleksaeedi, S.; Sapari, M. A. B.; Nai, M. L. S.; Meenashisundaram, G. K.; Gupta, M. Additive manufacturing of magnesium–zinc–zirconium (ZK) alloys via capillary-mediated binderless three-dimensional printing. Mater Des. 2019, 169, 107683.  
229. He, C.; Bin, S.; Wu, P.; Gao, C.; Feng, P.; Yang, Y.; Liu, L.; Zhou, Y.; Zhao, M.; Yang, S.; Shuai, C. Microstructure evolution and biodegradation behavior of laser rapid solidified Mg–Al–Zn alloy. Metals (Basel). 2017, 7, 105.  
230. Shuai, C.; He, C.; Feng, P.; Guo, W.; Gao, C.; Wu, P.; Yang, Y.; Bin, S. Biodegradation mechanisms of selective laser-melted Mg–xAl–Zn alloy: grain size and intermetallic phase. Virtual Phys Prototyp. 2018, 13, 59-69.  

Conflict of interest
The authors declare they have no competing interests.
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