Microstructure-modified biodegradable magnesium alloy for promoting cytocompatibility and wound healing in vitro

  • Da-Jun Lin
  • Fei-Yi HungEmail author
  • Ming-Long Yeh
  • Truan-Sheng Lui
Biocompatibility Studies Original Research
Part of the following topical collections:
  1. Biocompatibility Studies


The microstructure of biomedical magnesium alloys has great influence on anti-corrosion performance and biocompatibility. In practical application and for the purpose of microstructure modification, heat treatments were chosen to provide widely varying microstructures. The aim of the present work was to investigate the influence of the microstructural parameters of an Al-free Mg–Zn–Zr alloy (ZK60), and the corresponding heat-treatment-modified microstructures on the resultant corrosion resistance and biological performance. Significant enhancement in corrosion resistance was obtained in Al-free Mg–Zn–Zr alloy (ZK60) through 400 °C solid-solution heat treatment. It was found that the optimal condition of solid-solution treatment homogenized the matrix and eliminated internal defects; after which, the problem of unfavorable corrosion behavior was improved. Further, it was also found that the Mg ion-release concentration from the modified ZK60 significantly induced the cellular activity of fibroblast cells, revealing in high viability value and migration ability. The experimental evidence suggests that this system can further accelerate wound healing. From the perspective of specific biomedical applications, this research result suggests that the heat treatment should be applied in order to improve the biological performance.


Corrosion Resistance Magnesium Alloy Corrosion Current Density Bimodal Microstructure Anticorrosion Performance 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



The authors are grateful to The Instrument Center of National Cheng Kung University and Ministry of Science and Technology, 103-2221-E-006-066 for the financial support of this research.


  1. 1.
    Staiger MP, Pietak AM, Huadmai J, Dias G. Magnesium and its alloys as orthopedic biomaterials: a review. Biomaterials. 2006;27:1728–34.CrossRefGoogle Scholar
  2. 2.
    Hornberger H, Virtanen S, Boccaccini AR. Biomedical coatings on magnesium alloys—a review. Acta Biomater. 2012;8:2442–55.CrossRefGoogle Scholar
  3. 3.
    Zhang SX, Zhang XN, Zhao CL, Li JA, Song Y, Xie CY, et al. Research on an Mg-Zn alloy as a degradable biomaterial. Acta Biomater. 2010;6:626–40.CrossRefGoogle Scholar
  4. 4.
    Li ZJ, Gu XN, Lou SQ, Zheng YF. The development of binary Mg-Ca alloys for use as biodegradable materials within bone. Biomaterials. 2008;29:1329–44.CrossRefGoogle Scholar
  5. 5.
    Lin DJ, Hung FY, Lui TS, Yeh ML. Heat treatment mechanism and biodegradable characteristics of ZAX1330 Mg alloy. Materials science & engineering C, Materials for biological applications. 2015;51:300–8.CrossRefGoogle Scholar
  6. 6.
    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;89:651–6.CrossRefGoogle Scholar
  7. 7.
    Li X, Chu CL, Liu L, Liu XK, Bai J, Guo C, et al. Biodegradable poly-lactic acid based-composite reinforced unidirectionally with high-strength magnesium alloy wires. Biomaterials. 2015;49:135–44.CrossRefGoogle Scholar
  8. 8.
    Kirkland NT, Birbilis N, Staiger MP. Assessing the corrosion of biodegradable magnesium implants: a critical review of current methodologies and their limitations. Acta Biomater. 2012;8:925–36.CrossRefGoogle Scholar
  9. 9.
    Zhang WJ, Li MH, Chen Q, Hu WY, Zhang WM, Xin W. Effects of Sr and Sn on microstructure and corrosion resistance of Mg-Zr-Ca magnesium alloy for biomedical applications. Mater Design. 2012;39:379–83.CrossRefGoogle Scholar
  10. 10.
    Pu Z, Song GL, Yang S, Outeiro JC, Dillon OW, Puleo DA, et al. Grain refined and basal textured surface produced by burnishing for improved corrosion performance of AZ31B Mg alloy. Corros Sci. 2012;57:192–201.CrossRefGoogle Scholar
  11. 11.
    Aung NN, Zhou W. Effect of grain size and twins on corrosion behaviour of AZ31B magnesium alloy. Corros Sci. 2010;52:589–94.CrossRefGoogle Scholar
  12. 12.
    Janning C, Willbold E, Vogt C, Nellesen J, Meyer-Lindenberg A, Windhagen H, et al. Magnesium hydroxide temporarily enhancing osteoblast activity and decreasing the osteoclast number in peri-implant bone remodelling. Acta Biomater. 2010;6:1861–8.CrossRefGoogle Scholar
  13. 13.
    Sternberg K, Gratz M, Koeck K, Mostertz J, Begunk R, Loebler M, et al. Magnesium used in bioabsorbable stents controls smooth muscle cell proliferation and stimulates endothelial cells in vitro. J Biomed Mater Res B. 2012;100B:41–50.CrossRefGoogle Scholar
  14. 14.
    Nguyen TY, Cipriano AF, Guan RG, Zhao ZY, Liu H. In vitro interactions of blood, platelet, and fibroblast with biodegradable magnesium-zinc-strontium alloys. J Biomed Mater Res A. 2015;103(9):2974–86.CrossRefGoogle Scholar
  15. 15.
    Hartwig A. Role of magnesium in genomic stability. Mutat Res-Fund Mol M. 2001;475:113–21.CrossRefGoogle Scholar
  16. 16.
    Zreiqat H, Howlett CR, Zannettino A, Evans P, Schulze-Tanzil G, Knabe C, et al. Mechanisms of magnesium-stimulated adhesion of osteoblastic cells to commonly used orthopaedic implants. J Biomed Mater Res. 2002;62:175–84.CrossRefGoogle Scholar
  17. 17.
    Tapiero H, Tew KD. Trace elements in human physiology and pathology: zinc and metallothioneins. Biomed Pharmacother. 2003;57:399–411.CrossRefGoogle Scholar
  18. 18.
    ISO 10993-5 I. Biological evaluation of medical devices. Part 5 Tests for Cytotoxicity: In Vitro MethodsANSI/AAMI, Arlington, VA (1999).Google Scholar
  19. 19.
    Massalski TB. Binary alloy phase diagrams. Ohio: Am Soc Metals; 1986.Google Scholar
  20. 20.
    Song GL. Recent progress in corrosion and protection of magnesium alloys. Adv Eng Mater. 2005;7:563–86.CrossRefGoogle Scholar
  21. 21.
    Kannan MB, Raman RKS. In vitro degradation and mechanical integrity of calcium-containing magnesium alloys in modified-simulated body fluid. Biomaterials. 2008;29:2306–14.CrossRefGoogle Scholar
  22. 22.
    Stern M, Geary AL. Electrochemical polarization. 1. A theoretical analysis of the shape of polarization curves. J Electrochem Soc. 1957;104:56–63.CrossRefGoogle Scholar
  23. 23.
    Zhao MC, Liu M, Song GL, Atrens A. Influence of microstructure on corrosion of as-cast ZE41. Adv Eng Mater. 2008;10:104–11.CrossRefGoogle Scholar
  24. 24.
    Mueller WD, Nascimento ML, de Mele MFL. Critical discussion of the results from different corrosion studies of Mg and Mg alloys for biomaterial applications. Acta Biomater. 2010;6:1749–55.CrossRefGoogle Scholar
  25. 25.
    Cheng YL, Qin TW, Wang HM, Zhang Z. Comparison of corrosion behaviors of AZ31, AZ91, AM60 and ZK60 magnesium alloys. T Nonferr Metal Soc. 2009;19:517–24.CrossRefGoogle Scholar
  26. 26.
    Liu CL, Wang YJ, Zeng RC, Zhang XM, Huang WJ, Chu PK. In vitro corrosion degradation behaviour of Mg-Ca alloy in the presence of albumin. Corros Sci. 2010;52:3341–7.CrossRefGoogle Scholar
  27. 27.
    Walker GM, Duffus JH. Magnesium-Ions and the Control of the Cell-Cycle in Yeast. J Cell Sci. 1980;42:329–56.Google Scholar
  28. 28.
    Valerio P, Pereira MM, Goes AM, Leite MF. The effect of ionic products from bioactive glass dissolution on osteoblast proliferation and collagen production. Biomaterials. 2004;25:2941–8.CrossRefGoogle Scholar
  29. 29.
    Zhao N, Zhu DH. Endothelial responses of magnesium and other alloying elements in magnesium-based stent materials. Metallomics. 2015;7:113–23.CrossRefGoogle Scholar
  30. 30.
    Lange TS, Kirchberg J, Bielinsky AK, Leuker A, Bank I, Ruzicka T, et al. Divalent cations (Mg2+, Ca2+) differentially influence the beta 1 integrin-mediated migration of human fibroblasts and keratinocytes to different extracellular matrix proteins. Exp Dermatol. 1995;4:130–7.CrossRefGoogle Scholar
  31. 31.
    Grzesiak JJ, Pierschbacher MD. Changes in the concentrations of extracellular Mg++ and Ca++ down-regulate E-cadherin and up-regulate Alpha(2)Beta(1) integrin function, activating keratinocyte migration on type-I collagen. J Invest Dermatol. 1995;104:768–74.CrossRefGoogle Scholar
  32. 32.
    Rubin H. Magnesium: the missing element in molecular views of cell proliferation control. BioEssays. 2005;27:311–20.CrossRefGoogle Scholar
  33. 33.
    Hazelton B, Mitchell B, Tupper J. Calcium, magnesium, and growth-control in the Wi-38 human fibroblast cell. J Cell Biol. 1979;83:487–98.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  • Da-Jun Lin
    • 1
  • Fei-Yi Hung
    • 1
    Email author
  • Ming-Long Yeh
    • 2
  • Truan-Sheng Lui
    • 1
  1. 1.Department of Materials Science and EngineeringNational Cheng Kung UniversityTainanTaiwan
  2. 2.Department of Biomedical EngineeringNational Cheng Kung UniversityTainanTaiwan

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