A multi-material coating containing chemically-modified apatites for combined enhanced bioactivity and reduced infection via a drop-on-demand micro-dispensing technique

  • Poon Nian Lim
  • Zuyong Wang
  • Lei Chang
  • Toshiisa Konishi
  • Cleo Choong
  • Bow Ho
  • Eng San Thian
Biomaterials Synthesis and Characterization Original Research
Part of the following topical collections:
  1. Biomaterials Synthesis and Characterization


Prevention of infection and enhanced osseointegration are closely related, and required for a successful orthopaedic implant, which necessitate implant designs to consider both criteria in tandem. A multi-material coating containing 1:1 ratio of silicon-substituted hydroxyapatite and silver-substituted hydroxyapatite as the top functional layer, and hydroxyapatite as the base layer, was produced via the drop-on-demand micro-dispensing technique, as a strategic approach in the fight against infection along with the promotion of bone tissue regeneration. The homogeneous distribution of silicon-substituted hydroxyapatite and silver-substituted hydroxyapatite micro-droplets at alternate position in silicon-substituted hydroxyapatite-silver-substituted hydroxyapatite/hydroxyapatite coating delayed the exponential growth of Staphylococcus aureus for up to 24 h, and gave rise to up-regulated expression of alkaline phosphatase activity, type I collagen and osteocalcin as compared to hydroxyapatite and silver-substituted hydroxyapatite coatings. Despite containing reduced amounts of silicon-substituted hydroxyapatite and silver-substituted hydroxyapatite micro-droplets over the coated area than silicon-substituted hydroxyapatite and silver-substituted hydroxyapatite coatings, silicon-substituted hydroxyapatite-silver-substituted hydroxyapatite/hydroxyapatite coating exhibited effective antibacterial property with enhanced bioactivity. By exhibiting good controllability of distributing silicon-substituted hydroxyapatite, silver-substituted hydroxyapatite and hydroxyapatite micro-droplets, it was demonstrated that drop-on-demand micro-dispensing technique was capable in harnessing the advantages of silver-substituted hydroxyapatite, silicon-substituted hydroxyapatite and hydroxyapatite to produce a multi-material coating along with enhanced bioactivity and reduced infection.


Hydroxyapatite Osteocalcin Coated Sample Microbial Adhesion Vortexed Solution 
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.



This work was supported by the Ministry of Education Academic Research Fund (Singapore) Project number MOE2013-T2-1-074.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no competing interests.


  1. 1.
    Malchau H, Garellick G, Herberts P. The evidence from the swedish hip register. In: Breusch S, Malchau H, editors. The well-cemented total hip arthroplasty. Heidelberg: Springer; 2005. p. 291–9.CrossRefGoogle Scholar
  2. 2.
    Jaekel D, Ong K, Lau E, Watson H, Kurtz S. Epidemiology of total hip and knee arthroplasty infection. In: Springer BD, Parvizi J, editors. Periprosthetic joint infection of the hip and knee. New York: Springer; 2014. p. 1–14.CrossRefGoogle Scholar
  3. 3.
    Harris LG, Richards RG. Staphylococci and implant surfaces: a review. Injury. 2006;37:S3–14.CrossRefGoogle Scholar
  4. 4.
    Kuijer R, Jansen EJP, Emans PJ, Bulstra SK, Riesle J, Pieper J, Grainger DW, Busscher HJ. Assessing infection risk in implanted tissue-engineered devices. Biomaterials. 2007;28:5148–54.CrossRefGoogle Scholar
  5. 5.
    Legeros RZ. Apatites in biological systems. Prog Crstal Growth Charact. 1981;4:1–45.CrossRefGoogle Scholar
  6. 6.
    Gibson IR, Best SM, Bonfield W. Chemical characterization of silicon-substituted hydroxyapatite. J Biomed Mater Res. 1999;44:422–8.CrossRefGoogle Scholar
  7. 7.
    Thian ES, Huang J, Vickers M, Best SM, Barber Z, Bonfield W. Silicon-substituted hydroxyapatite (SiHA): A novel calcium phosphate coating for biomedical applications. J Mater Sci. 2006;41:709–17.CrossRefGoogle Scholar
  8. 8.
    Huang J, Best SM, Bonfield W, Buckland T. Development and characterization of titanium-containing hydroxyapatite for medical applications. Acta Biomater. 2010;6:241–9.CrossRefGoogle Scholar
  9. 9.
    Evis Z, Webster TJ. Nanosize hydroxyapatite: doping with various ions. Adv Appl Ceram. 2011;110:311–21.CrossRefGoogle Scholar
  10. 10.
    Shepherd JH, Shepherd DV, Best SM. Substituted hydroxyapatites for bone repair. J Mater Sci Mater Med. 2012;23:2335–47.CrossRefGoogle Scholar
  11. 11.
    Shepherd DV, Best SM. Production of zinc substituted hydroxyapatite using various precipitation routes. Biomed Mater. 2013;8:025003CrossRefGoogle Scholar
  12. 12.
    Šupová M. Substituted hydroxyapatites for biomedical applications: a review. Ceram Int. 2015;41:9203–31.CrossRefGoogle Scholar
  13. 13.
    Friederichs RJ, Chappell HF, Shepherd DV, Best SM. Synthesis, characterization and modelling of zinc and silicate co-substituted hydroxyapatite. J R Soc Interface. 2015;12.Google Scholar
  14. 14.
    Ratnayake JTB, Mucalo M, Dias GJ. Substituted hydroxyapatites for bone regeneration: a review of current trends. J Biomed Mater Res B Appl Biomater. 2016. doi: 10.1002/jbm.b.33651.Google Scholar
  15. 15.
    Singh B, Dubey AK, Kumar S, Saha N, Basu B, Gupta R. In vitro biocompatibility and antimicrobial activity of wet chemically prepared Ca10−xAgx(PO4)6(OH)2 (0.0 ≤ x ≤ 0.5) hydroxyapatites. Mater Sci Eng C. 2011;31:1320–9.CrossRefGoogle Scholar
  16. 16.
    Rameshbabu N, Kumar TSS, Prabhakar TG, Sastry VS. Murty KVGK, Rao KP. Antibacterial nanosized silver substituted hydroxyapatite: Synthesis and characterization. J Biomed Mater Res A. 2007;80A:581–91.CrossRefGoogle Scholar
  17. 17.
    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.CrossRefGoogle Scholar
  18. 18.
    Sprio S, Tampieri A, Landi E, Sandri M, Martorana S, Celotti G, Logroscino G. Physico-chemical properties and solubility behaviour of multi-substituted hydroxyapatite powders containing silicon. Mater Sci Eng C. 2008;28:179–87.CrossRefGoogle Scholar
  19. 19.
    Kim SR, Lee JH, Kim YT, Riu DH, Jung SJ, Lee YJ, Chung SC, Kim YH. Synthesis of Si, Mg substituted hydroxyapatites and their sintering behaviors. Biomaterials. 2003;24:1389–98.CrossRefGoogle Scholar
  20. 20.
    Gibson IR, Bonfield W. Preparation and characterization of magnesium/carbonate co-substituted hydroxyapatites. J Mater Sci Mater Med. 2002;13:685–93.CrossRefGoogle Scholar
  21. 21.
    De Maeyer EAP, Verbeeck RMH. Possible substitution mechanisms for sodium and carbonate in calciumhydroxyapatite. B Soc Chim Belg. 1993;102:601–9.CrossRefGoogle Scholar
  22. 22.
    Zhang L, Li H, Li K, Liu S, Zhang Y, Yao P, Zhang W, Chen G. Multi-layer SiC/Mg and F co-substituted hydroxyapatite/chitosan bioactive coating for carbon fibers. Mater Lett. 2016;164:360–3.CrossRefGoogle Scholar
  23. 23.
    Han Y, Chen DH, Zhang L. Nanocrystallized SrHA/SrHA–SrTiO3 /SrTiO3 –TiO2 multilayer coatings formed by micro-arc oxidation for photocatalytic application. Nanotechnol. 2008;19:335705CrossRefGoogle Scholar
  24. 24.
    Tomaszek R, Pawlowski L, Gengembre L, Laureyns J, Le Maguer A. Microstructure of suspension plasma sprayed multilayer coatings of hydroxyapatite and titanium oxide. Surf Coat Technol. 2007;201:7432–40.CrossRefGoogle Scholar
  25. 25.
    Chang L, Sun J, Fuh JYH, Thian ES. Deposition and characterization of a dual-layer silicon- and silver-containing hydroxyapatite coating via a drop-on-demand technique. RSC Adv. 2013;3:11162–8.CrossRefGoogle Scholar
  26. 26.
    Hayek E, Newesely H, Rumpel ML, Pentacalcium Monohydroxyorthophosphate. In: Kleinberg J, editor. Inorganic Syntheses. John Wiley & Sons, Inc., Hoboken, NJ, USA. 2007. pp. 63–5.Google Scholar
  27. 27.
    Lim PN, Teo EY, Ho B, Tay BY, Thian ES. Effect of silver content on the antibacterial and bioactive properties of silver-substituted hydroxyapatite. J Biomed Mater Res A. 2013;101A:2456–64.CrossRefGoogle Scholar
  28. 28.
  29. 29.
    Poelstra KA, Barekzi NA, Rediske AM, Felts AG, Slunt JB, Grainger DW. Prophylactic treatment of gram-positive and gram-negative abdominal implant infections using locally delivered polyclonal antibodies. J Biomed Mater Res. 2002;60:206–15.CrossRefGoogle Scholar
  30. 30.
    Schwarz K. Proceedings: recent dietary trace element research, exemplified by tin, fluorone, and silicon. Fed Proc. 1974;33:1748–57.Google Scholar
  31. 31.
    Han P, Wu C, Xiao Y. The effect of silicate ions on proliferation, osteogenic differentiation and cell signalling pathways (WNT and SHH) of bone marrow stromal cells. Biomater Sci. 2013;1:379–92.CrossRefGoogle Scholar
  32. 32.
    Birchall JDEA. Biological implications of the interaction (via silanol groups) of silicon with metal ions. Ciba Found Symp. 1986;121:140–59.Google Scholar

Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Poon Nian Lim
    • 1
  • Zuyong Wang
    • 1
  • Lei Chang
    • 1
  • Toshiisa Konishi
    • 1
    • 2
  • Cleo Choong
    • 3
  • Bow Ho
    • 4
  • Eng San Thian
    • 1
  1. 1.Department of Mechanical EngineeringNational University of SingaporeSingaporeSingapore
  2. 2.Graduate School of Natural Science and TechnologyOkayama UniversityOkayamaJapan
  3. 3.School of Materials Science and Engineering, Nanyang Technology UniversitySingaporeSingapore
  4. 4.Department of Microbiology and Immunology, Yong Loo Lin School of MedicineNational University of SingaporeSingaporeSingapore

Personalised recommendations