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Systematical evolution on a Zn–Mg alloy potentially developed for biodegradable cardiovascular stents

  • Biomaterials Synthesis and Characterization
  • Original Research
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Abstract

To reduce the long-term side effects of permanent metallic stents, a new generation of cardiovascular stents called “biodegradable stents” is being extensively developed. Zinc has been considered as a promising candidate material for biodegradable cardiovascular stents due to its excellent biocompatibility and appropriate biodegradability. However, weak mechanical properties limit its further clinic application. In this study, hot extruded pure Zn and Zn-0.02 Mg alloy were prepared. Compared with pure Zn, Zn-0.02 Mg alloy showed more homogeneous microstructure, much smaller grain size and higher mechanical strength. Zn-0.02 Mg alloy presented uniform corrosion morphologies during the immersion process, and its corrosion rates was higher than that of pure Zn. Hemocompatibility results showed that the Zn-based alloy had extremely low hemolysis rate (0.74 ± 0.15%) and strong inhibitory effect on blood coagulation, platelet adhesion and aggregation. Zn-0.02 Mg alloy also exhibited excellent cytocompatibility. Its extracts could significantly promote the proliferation of endothelial cells. Moreover, the antibacterial activities of the Zn-based alloy were demonstrated by spread plate assay, live/dead viability assay and bacterial morphology observation. These results indicate that the extruded Zn-0.02 Mg alloy has a potential in biodegradable cardiovascular stents.

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References

  1. Laslett LJ, Alagona P, Clark BA, Drozda JP, Saldivar F, Wilson SR, et al. The worldwide environment of cardiovascular disease: prevalence, diagnosis, therapy, and policy issues: a report from the American College of Cardiology. J Am Coll Cardiol. 2012;60:S1–49.

    Article  Google Scholar 

  2. Yahagi K, Kolodgie FD, Otsuka F, Finn AV, Davis HR, Joner M, et al. Pathophysiology of native coronary, vein graft, and in-stent atherosclerosis. Nat Rev Cardiol. 2016;13:79–98.

    Article  CAS  Google Scholar 

  3. Hu T, Yang J, Cui K, Rao Q, Yin T, Tan L, et al. Controlled slow-release drug-eluting stents for the prevention of coronary restenosis: recent progress and future prospects. ACS Appl Mater Interfaces. 2015;7:11695–712.

    Article  CAS  Google Scholar 

  4. Dangas GD, Claessen BE, Caixeta A, Sanidas EA, Mintz GS, Mehran R. In-stent restenosis in the drug-eluting stent era. J Am Coll Cardiol. 2010;56:1897–907.

    Article  Google Scholar 

  5. Hu T, Lin S, Du R, Fu M, Rao Q, Yin T, et al. Design, preparation and performance of a novel drug-eluting stent with multiple layer coatings. Biomater Sci. 2017;5:1845–57.

    Article  CAS  Google Scholar 

  6. Kereiakes DJ, Cox DA, Hermiller JB, Midei MG, Bachinsky WB, Nukta ED, et al. Usefulness of a cobalt chromium coronary stent alloy. Am J Cardiol. 2003;92:463–6.

    Article  CAS  Google Scholar 

  7. Barth KH, Virmani R, Froelich J, Takeda T, Lossef SV, Newsome J, et al. Paired comparison of vascular wall reactions to Palmaz stents, Strecker tantalum stents, and Wallstents in canineiliac and femoral arteries. Circulation. 1996;93:2161–9.

    Article  CAS  Google Scholar 

  8. Cook S, Wenaweser P, Togni M, et al. Incomplete stent apposition and very late stent thrombosis after drug-eluting stent implantation. Circulation. 2007;115:2426–34.

    Article  CAS  Google Scholar 

  9. Farb A, Weber DK, Kolodgie FD, Burke AP, Virmani R. Morphological predictors of restenosis after coronary stenting in humans. Circulation. 2002;105:2974–80.

    Article  Google Scholar 

  10. Finn AV, Virmani R. The clinical challenge of disappearing stents. Lancet. 2016;387:510–2.

    Article  Google Scholar 

  11. Chung WS, Park CS, Seung KB, Kim PJ, Lee JM, Koo BK, et al. The incidence and clinical impact of stent strut fractures developed after drug-eluting stent implantation. Int J Cardiol. 2008;125:325–31.

    Article  Google Scholar 

  12. Waksman R. Update on bioabsorbable stents: from bench to clinical. J Inter Cardiol. 2006;19:414–21.

    Article  Google Scholar 

  13. Yue Y, Wang L, Yang N, Huang J, Lei L, Ye H, et al. Effectiveness of biodegradable magnesium alloy stents in coronary artery and femoral artery. J Inter Cardiol. 2015;28:358–64.

    Article  Google Scholar 

  14. Bowen PK, Shearier ER, Zhao S, Guillory RJ, Zhao F, Goldman J, et al. Biodegradable metals for cardiovascular stents: from clinical concerns to recent Zn-alloys. Adv Health Mater. 2016;5:1121–40.

    Article  CAS  Google Scholar 

  15. Wykrzykowska JJ, Kraak RP, Hofma SH, van der Schaaf RJ, Arkenbout EK, IJsselmuiden AJ, et al. Bioresorbable scaffolds versus metallic stents in routine PCI. N Engl J Med. 2017;376:2319–28.

    Article  CAS  Google Scholar 

  16. Montone RA, Niccoli G, De Marco F, Minelli S, D’Ascenzo F, Testa L, et al. Temporal trends in adverse events after everolimus-eluting bioresorbable vascular scaffold versus everolimus-eluting metallic stent implantation: a meta-analysis of randomized controlled trials. Circulation. 2017;135:2145–54.

    Article  CAS  Google Scholar 

  17. Zheng YF, Gu XN, Witte F. Biodegradable metals. Mater Sci Eng R. 2014;77:1–34.

    Article  Google Scholar 

  18. Gu X, Zheng Y, Cheng Y, Zhong S, Xi T. In vitro corrosion and biocompatibility of binary magnesium alloys. Biomaterials. 2009;30:484–98.

    Article  CAS  Google Scholar 

  19. Silva CLP, Oliveira AC, Costa CGF, Figueiredo RB, Leite MF, Pereira MM, et al. Effect of severe plastic deformation on the biocompatibility and corrosion rate of pure magnesium. J Mater Sci. 2017;52:5992–6003.

    Article  CAS  Google Scholar 

  20. Pierson D, Edick J, Tauscher A, Pokorney E, Bowen P, Gelbaugh J, et al. A simplified in vivo approach for evaluating the bioabsorbable behavior of candidate stent materials. J Biomed Mater Res B Appl Biomater. 2012;100:58–67.

    Article  CAS  Google Scholar 

  21. Tapiero H, Tew KD. Trace elements in human physiology and pathology: zinc and metallothioneins. Biomed Pharmacother. 2003;57:399–411.

    Article  CAS  Google Scholar 

  22. Prasad AS. Zinc in human health: effect of zinc on immune cells. Mol Med. 2008;14:353–7.

    Article  CAS  Google Scholar 

  23. Powell SR, Hambidge M, Cousins RJ, Costello RB. The antioxidant properties of zinc. J Nutr. 2000;130:1447s–54s.

    Article  CAS  Google Scholar 

  24. Meika F, Samir S. Zinc and regulation of inflammatory cytokines: implications for cardiometabolic disease. Nutrients. 2012;4:676–94.

    Article  CAS  Google Scholar 

  25. Meerarani P, Reiterer G, Toborek M, Hennig B. Zinc modulates PPARγ21 signaling and activation of porcine endothelial cells. J Nutr. 2003;133:3058–64.

    Article  CAS  Google Scholar 

  26. Hennig B, Toborek M, Mcclain CJ. Antiatherogenic properties of zinc: implications in endothelial cell metabolism. Nutrition. 1996;12:711–7.

    Article  CAS  Google Scholar 

  27. Bowen PK, Drelich J, Goldman J. Zinc exhibits ideal physiological corrosion behavior for bioabsorbable stents. Adv Mater. 2013;25:2577–82.

    Article  CAS  Google Scholar 

  28. Bowen PK, Guillory RJ, Shearier ER, Seitz JM, Drelich J, Bocks M, et al. Metallic zinc exhibits optimal biocompatibility for bioabsorbable endovascular stents. Mater Sci Eng C Mater Biol Appl. 2015;56:467–72.

    Article  CAS  Google Scholar 

  29. Drelich AJ, Zhao S, Guillory RJ, Drelich JW, Goldman J. Long-term surveillance of zinc implant in murine artery: surprisingly steady biocorrosion rate. Acta Biomater. 2017;58:539–49.

    Article  CAS  Google Scholar 

  30. Yang H, Wang C, Liu C, Chen H, Wu Y, Han J, et al. Evolution of the degradation mechanism of pure zinc stent in the one-year study of rabbit abdominal aorta model. Biomaterials. 2017;145:92–105.

    Article  CAS  Google Scholar 

  31. Gong H, Wang K, Strich R, Zhou JG. In vitro biodegradation behavior, mechanical properties, and cytotoxicity of biodegradable Zn-Mg alloy. J Biomed Mater Res B Appl Biomater. 2015;103:1632–40.

    Article  CAS  Google Scholar 

  32. Wang LQ, Ren YP, Sun SN, Zhao H, Li S, Qin GW. Microstructure, mechanical properties and fracture behavior of as-extruded Zn-Mg binary alloys. Acta Met Sin. 2017;30:931–40.

    Article  CAS  Google Scholar 

  33. Li HF, Xie XH, Zheng YF, Cong Y, Zhou FY, Qiu KJ, et al. Development of biodegradable Zn-1X binary alloys with nutrient alloying elements Mg, Ca and Sr. Sci Rep. 2015;5:10719.

    Article  Google Scholar 

  34. ASTM, ASTM-E8/E8m-11: standard test methods for tension testing of metallic materials, annual book of ASTM standards. ASTM, USA; 2011.

  35. ASTM, ASTM-G102-89: standard practice for calculation of corrosion rates and related information from electrochemical measurements. annual book of ASTM standards. ASTM, USA; 2004.

  36. ASTM, ASTM-G31-72: standard practice for laboratory immersion corrosion testing of metals, annual book of ASTM standards. ASTM, USA; 2004.

  37. IOS, ISO 10993-12: biological evaluation of medical devices-part 12: sample preparation and reference materials. IOS, Switzerland; 2012.

  38. Lin S, Wang Q, Yan X, Ran X, Wang L, Zhou JG, et al. Mechanical properties, degradation behaviors and biocompatibility evaluation of a biodegradable Zn-Mg-Cu alloy for cardiovascular implants. Mater Lett. 2019;234:294–7.

    Article  CAS  Google Scholar 

  39. ASTM, ASTM-F756-08: Standard Practice for Assessment of Hemolytic Properties of Materials, Annual Book of ASTM Standards. ASTM, USA; 2008.

  40. IOS, ISO 10993-5: biological evaluation of medical devices-part 5: tests for in vitro cytotoxicity. IOS, Switzerland; 2009.

  41. Hermawan H, Dubé D, Mantovani D. Developments in metallic biodegradable stents. Acta Biomater. 2010;6:1693–7.

    Article  CAS  Google Scholar 

  42. Trumbo P, Yates AA, Schlicker S, Poos M. Dietary reference intakes: vitamin A, vitamin K, arsenic, boron, chromium, copper, iodine, iron, manganese, molybdenum, nickel, silicon, vanadium, and zinc. J Am Diet Assoc. 2001;101:294–301.

    Article  CAS  Google Scholar 

  43. Monchaux E, Vermette P. Effects of surface properties and bioactivation of biomaterials on endothelial cells. Front Biosci. 2010;2:239–55.

    Google Scholar 

  44. Huang N, Yang P, Leng YX, Chen JY, Sun H, Wang J, et al. Hemocompatibility of titanium oxide films. Biomaterials. 2003;24:2177–87.

    Article  CAS  Google Scholar 

  45. Darouiche RO. Treatment of infections associated with surgical implants. N Engl J Med. 2004;350:1422–9.

    Article  CAS  Google Scholar 

  46. Ning C, Wang X, Li L, Zhu Y, Li M, Yu P, et al. Concentration ranges of antibacterial cations for showing the highest antibacterial efficacy but the least cytotoxicity against mammalian cells: implications for a new antibacterial mechanism. Chem Res Toxicol. 2015;28:1815–22.

    Article  CAS  Google Scholar 

  47. Phan TN, Buckner T, Sheng J, Baldeck JD, Marquis RE. Physiologic actions of zinc related to inhibition of acid and alkali production by oral streptococci in suspensions and biofilms. Oral Microbiol Immunol. 2004;19:31–8.

    Article  CAS  Google Scholar 

  48. Scheie AA, Assev S, Rölla G. Combined effect of xylitol, NaF and ZnCl2 on growth and metabolism of Streptococcus sobrinus OMZ 176. APMIS. 1988;96:761.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

The work was supported by grants from the National Key Technology R & D Program of China (2016YFC1102305), Chongqing Science and Technology Bureau (cstc2019jcyj-zdxm0033), the National Natural Science Foundation of China (11332003). We are also thankful for the support from the Chongqing Engineering Laboratory in Vascular Implants, the Public Experiment Centre of State Bioindustrial Base (Chongqing) and the National “111 plan” (B06023). The authors also acknowledges the kind assistance of Dr Haijun Zhang and MSc Yuxia Yin from National United Engineering Laboratory for Biomedical Material Modification, China in collection and analysis of experimental data as well as discussion on revised manuscript.

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Authors and Affiliations

  1. Key Laboratory for Biorheological Science and Technology of Ministry of Education, State and Local Joint Engineering Laboratory for Vascular Implants, Bioengineering College of Chongqing University, Chongqing, 400030, China

    Song Lin, Xiaolin Ran, Qilong Wang, Tingzhang Hu & Guixue Wang

  2. Xi’an Advanced Medical Technology Co., Ltd, Xi’an, 710000, China

    Xinhao Yan & Jack G. Zhou

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  1. Song Lin
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Lin, S., Ran, X., Yan, X. et al. Systematical evolution on a Zn–Mg alloy potentially developed for biodegradable cardiovascular stents. J Mater Sci: Mater Med 30, 122 (2019). https://doi.org/10.1007/s10856-019-6324-9

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