Skip to main content

Advertisement

SpringerLink
Log in

Zinc-substituted hydroxyapatite: a biomaterial with enhanced bioactivity and antibacterial properties

  • Published:
Journal of Materials Science: Materials in Medicine Aims and scope Submit manuscript

Abstract

Hydroxyapatite (HA) is a synthetic biomaterial and has been found to promote new bone formation when implanted in a bone defect site. However, its use is often limited due to its slow osteointegration rate and low antibacterial activity, particularly where HA has to be used for long term biomedical applications. This work will describe the synthesis and detailed characterization of zinc-substituted HA (ZnHA) as an alternative biomaterial to HA. ZnHA containing 1.6 wt% Zn was synthesized via a co-precipitation reaction between calcium hydroxide, orthophosphoric acid and zinc nitrate hexahydrate. Single-phase ZnHA particles with a rod-like morphology measuring ~50 nm in length and ~15 nm in width, were obtained and characterized using transmission electron microscopy and X-ray diffraction. The substitution of Zn into HA resulted in a decrease in both the a- and c-axes of the unit cell parameters, thereby causing the HA crystal structure to alter. In vitro cell culture work showed that ZnHA possessed enhanced bioactivity since an increase in the growth of human adipose-derived mesenchymal stem cells along with the bone cell differentiation markers, were observed. In addition, antibacterial work demonstrated that ZnHA exhibited antimicrobial capability since there was a significant decrease in the number of viable Staphylococcus aureus bacteria after in contact with ZnHA.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9
Fig. 10

Similar content being viewed by others

References

  1. De Groot K, Wolke J. Calcium phosphate coatings for medical implants. Proc Instn Mech Eng. 1998;212H:137–47.

    Google Scholar 

  2. Oonishi H. Orthopaedic applications of hydroxyapatite. Biomaterials. 1991;12:171–8.

    Article  CAS  Google Scholar 

  3. Oonishi H, Hench LL, Wilson J, Sugihara F, Tsuji E, Kushitani S, Iwaki H. Comparative bone growth behavior in granules of bioceramic materials of various sizes. J Biomed Mater Res. 1999;44:31–43.

    Article  CAS  Google Scholar 

  4. Darouiche RO. Treatment of infections associated with surgical implants. Infect Dis Clin Pract. 2004;12:258–9.

    Google Scholar 

  5. Yazdi M, Bernick S, Paule W, Nimni M. Postmortem degradation of demineralised bone matrix osteoinductive potential: effect of time and storage temperature. Clin Orthop Relat Res. 1991;262:281–5.

    Google Scholar 

  6. Thian ES, Huang J, Best SM, Barber ZH, Brooks RA, Rushton N, Bonfield W. The response of osteoblasts to nanocrystalline silicon-substituted hydroxyapatite thin films. Biomaterials. 2006;27:2692–8.

    Article  CAS  Google Scholar 

  7. Porter AE, Patel N, Skepper JN, Best SM, Bonfield W. Effect of sintered silicate-substituted hydroxyapatite on remodelling processes at the bone-implant interface. Biomaterials. 2004;25:3303–14.

    Article  CAS  Google Scholar 

  8. Patel N, Best SM, Bonfield W, Gibson IR, Hing KA, Damien E, Revell PA. A comparative study on the in vivo behavior of hydroxyapatite and silicon substituted hydroxyapatite granules. J Mater Sci Mater Med. 2002;13:1199–206.

    Article  CAS  Google Scholar 

  9. Chen Y, Zheng X, Xie Y, Ji H, Ding C, Li H, Dai K. Silver release from silver-containing hydroxyapatite coatings. Surf Coat Tech. 2010;205:1892–6.

    Article  CAS  Google Scholar 

  10. Rameshbabu N, Kumar TSS, Prabhakar TG, Sastry VS, Murty KVGK, Rao KP. Antibacterial nanosized silver substituted hydroxyapatite: synthesis and characterization. J Biomed Mater Res. 2007;80A:581–91.

    Article  CAS  Google Scholar 

  11. Kim TN, Feng QL, Kim JO, Wu J, Wang H, Chen GC, Cui FZ. Antimicrobial effects of metal ions (Ag+, Cu2+, Zn2+) in hydroxyapatite. J Mater Sci Mater Med. 1998;9:129–34.

    Article  Google Scholar 

  12. Ito A, Otsuka M, Kawamura H, Ikeuchi M, Ohgushi H, Sogo Y, Ichinose N. Zinc-containing tricalcium phosphate and related materials for promoting bone formation. Curr Appl Phys. 2005;5:402–6.

    Article  Google Scholar 

  13. Rossi L, Migliaccio S, Corsi A, Marzia M, Bianco P, Teti A, Gambelli L, Cianfarani S, Paoletti F, Branca F. Reduced growth plate activity and inanition. J Nutr. 2001;131:1142–6.

    CAS  Google Scholar 

  14. Moonga BS, Dempster DW. Zinc is a potent inhibitor of osteoclastic bone resorption in vitro. J Bone Min Res. 1995;10:453–7.

    Article  CAS  Google Scholar 

  15. Yamaguchi M, Oishi H, Suketa Y. Stimulatory effect of zinc on bone formation in tissue culture. Biochem Pharma. 1987;36:4007–12.

    Article  CAS  Google Scholar 

  16. Miyaji F, Kono Y, Suyama Y. Formation and structure of zinc-substituted calcium hydroxyapatite. Mater Res Bull. 2005;40:209–20.

    Article  CAS  Google Scholar 

  17. Webster TJ, Massa-Schlueter EA, Smith JL, Slamovich EB. Osteoblast response to hydroxyapatite doped with divalent and trivalent cations. Biomaterials. 2004;25:2111–21.

    Article  CAS  Google Scholar 

  18. Sogo Y, Ito A, Fukasawa K, Sakurai T, Ichinose N. Zinc containing hydroxyapatite ceramics to promote osteoblastic cell activity. Mater Sci Tech. 2004;20:1079–83.

    Article  CAS  Google Scholar 

  19. Ergun C, Webster TJ, Bizios R, Doremus RH. Hydroxylapatite with substituted magnesium, zinc, cadmium, and yttrium. I. Structure and microstructure. J Biomed Mater Res. 2002;59:305–11.

    Article  CAS  Google Scholar 

  20. Chung R, Hsieh M, Huang C, Perng L, Wen H, Chin T. Antimicrobial effect and human gingival biocompatibility of hydroxyapatite sol-gel coatings. J Biomed Mater Res. 2006;76B:169–78.

    Article  CAS  Google Scholar 

  21. Ren F, Xin R, Ge X, Leng Y. Characterization and structural analysis of zinc-substituted hydroxyapatites. Acta Biomater. 2009;5:3141–9.

    Article  CAS  Google Scholar 

  22. Li MO, Xiao X, Liu R, Chen C, Huang L. Structural characterization of zinc-substituted hydroxyapatite prepared by hydrothermal method. J Mater Sci Mater Med. 2008;19:797–803.

    Article  CAS  Google Scholar 

  23. Bigi A, Foresti E, Gandolfi M, Gazzano M, Roveri N. Inhibiting effect of zinc on hydroxyapatite crystallisation. J Inorg Biochem. 1995;58:49–58.

    Article  CAS  Google Scholar 

  24. LeGeros R, LeGeros J. Dense hydroxyapatite. In: Hench LL, Wilson J, editors. An introduction to bioceramics. Singapore: World Scientific; 1993. p. 139–80.

    Chapter  Google Scholar 

  25. Wang X, Ito A, Sogo Y, Li X, Oyane A. Zinc-containing apatite layers on external fixation rods promoting cell activity. Acta Biomater. 2010;6:962–8.

    Article  CAS  Google Scholar 

  26. Stanić V, Dimitrijević S, Antić-Stanković J, Mitrić M, Jokić B, Plećaš I, Raičević S. Synthesis, characterization and antimicrobial activity of copper and zinc-doped hydroxyapatite nanopowders. Appl Surf Sci. 2010;256:6083–9.

    Article  Google Scholar 

  27. Sogo Y, Sakurai T, Onuma K, Ito A. The most appropriate (Ca + Zn)/P molar ratio to minimize the zinc content of ZnTCP/HAP ceramic used in the promotion of bone formation. J Biomed Mater Res. 2002;62:457–63.

    Article  CAS  Google Scholar 

  28. Ito A, Ojima K, Naito H, Ichinose N, Tateishi T. Preparation, solubility, and cytocompatibility of zinc-releasing calcium phosphate ceramics. J Biomed Mater Res. 2000;50:178–83.

    Article  CAS  Google Scholar 

  29. Yamada Y, Ito A, Kojima H, Sakane M, Miyakawa S, Uemura T, LeGeros RZ. Inhibitory effect of Zn2+ in zinc-containing β-tricalcium phosphate on resorbing activity of mature osteoclasts. J Biomed Mater Res. 2008;84A:344–52.

    Article  CAS  Google Scholar 

  30. Kawamura H, Ito A, Miyakawa S, Layrolle P, Ojima K, Ichinose N, Tateishi T. Stimulatory effect of zinc-releasing calcium phosphate implant on bone formation in rabbit femoral. J Biomed Mater Res. 2000;50:184–90.

    Article  CAS  Google Scholar 

  31. Kay MI, Young RA, Posner AS. Crystal structure of hydroxyapatite. Nature. 1964;204:1050–2.

    Article  CAS  Google Scholar 

  32. Hayakawa S, Ando K, Tsuru K, Osaka A, Fujii E, Kawabata K, Bonhomme C, Babonneau F. Structural characterization and protein adsorption property of hydroxyapatite particles modified with zinc ions. J Am Ceram Soc. 2007;90:565–9.

    Article  CAS  Google Scholar 

  33. Rehman I, Bonfield W. Characterization of hydroxyapatite and carbonated apatite by photo acoustic FTIR spectroscopy. J Mater Sci Mater Med. 1997;8:1–4.

    Article  CAS  Google Scholar 

  34. Swetha M, Sahithi K, Moorthi A, Saranya N, Saravanan S, Ramasamy K, Srinivasan N, Selvamurugan N. Synthesis, characterization, and antimicrobial activity of nano-hydroxyapatite-zinc for bone tissue engineering applications. J Nanosci Nanotech. 2012;12:167–72.

    Article  CAS  Google Scholar 

  35. Du WL, Xu YL, Xu ZR, Fan CL. Preparation, characterization and antibacterial properties against E. coli K 88 of chitosan nanoparticle loaded copper ions. Nanotechnology. 2008;19:085707.

    Article  Google Scholar 

  36. Nan L, Liu Y, Lü M, Yang K. Study on antibacterial mechanism of copper-bearing austenitic antibacterial stainless steel by atomic force microscopy. J Mater Sci Mater Med. 2008;19:3057–62.

    Article  CAS  Google Scholar 

Download references

Acknowledgments

This research was supported by Hitachi Scholarship Foundation (Japan) under Research Fellowship HSF-R126.

Author information

Authors and Affiliations

  1. Department of Mechanical Engineering, National University of Singapore, 9 Engineering Drive 1, Singapore, 117 576, Singapore

    E. S. Thian & P. N. Lim

  2. Kanagawa Academy of Science and Technology (KAST), 3-2-1 Sakado, Takatsu-ku, Kawasaki, Kanagawa, 213-0012, Japan

    E. S. Thian, T. Konishi, Y. Kawanobe & M. Aizawa

  3. Department of Applied Chemistry, School of Science and Technology, Meiji University, 1-1-1 Higashimita, Tama-ku, Kawasaki, Kanagawa, 214-8571, Japan

    Y. Kawanobe & M. Aizawa

  4. School of Materials Science and Engineering, Nanyang Technological University, 50 Nanyang Avenue, Singapore, 639 798, Singapore

    C. Choong

  5. Department of Mircobiology, National University of Singapore, 10 Kent Ridge Crescent, Singapore, 119 260, Singapore

    B. Ho

Authors
  1. E. S. Thian
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. T. Konishi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Y. Kawanobe
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. P. N. Lim
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. C. Choong
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. B. Ho
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. M. Aizawa
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to E. S. Thian.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Thian, E.S., Konishi, T., Kawanobe, Y. et al. Zinc-substituted hydroxyapatite: a biomaterial with enhanced bioactivity and antibacterial properties. J Mater Sci: Mater Med 24, 437–445 (2013). https://doi.org/10.1007/s10856-012-4817-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10856-012-4817-x

Keywords

Search

Navigation