Skip to main content

Advertisement

SpringerLink
Log in

In vitro antimicrobial activity of vancomycin-eluting bioresorbable β-TCP-polylactic acid nanocomposite material for load-bearing bone repair

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

Abstract

Release of antimicrobial agents from bone healing devices can dramatically reduce the risk of implant-associated infection. Here we report the fabrication and antimicrobial activity of a multifunctional load-bearing bioresorbable material that can provide mechanical support to the healing bone all while slowly releasing an antibiotic drug. Dense beta-tricalcium phosphate (β-TCP)–40 vol% polylactic acid (PLA) nanocomposite containing 1 wt% vancomycin (VH) was high pressure consolidated at 2.5 GPa, at room temperature, or at 120 °C. Over the course of 5 weeks in TRIS solution, the β-TCP-PLA-VH nanocomposite released approximately 90 % of its drug load. Specimens consolidated at 120 °C had the highest initial mechanical properties and maintained 85 % of their compressive strength and 30 % of their bending strength after 5 weeks release. In vitro growth inhibition study showed significant antimicrobial efficacy of VH-impregnated β-TCP-PLA against methicillin-resistant Staphylococcus aureus when exposed to both high (2 × 105 CFU/mL) and very high (1 × 108 CFU/mL) bacterial concentrations. After 1 week, total eradication of the microorganisms was achieved. The results suggest that the developed high-strength antibiotic-eluting β-TCP-PLA nanocomposite can be a promising material for orthopedic surgical devices.

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

Similar content being viewed by others

References

  1. Middleton JC, Tipton AJ. Synthetic biodegradable polymers as orthopedic devices. Biomaterials. 2000;21:2335–46.

    Article  CAS  Google Scholar 

  2. Takayama T, Todo M. Improvement of mechanical properties of poly(L-lactic acid) by blending of lysine triisocyanate. J Mater Sci. 2009;44:5017–20.

    Article  CAS  Google Scholar 

  3. Kasuga T, Ota Y, Nogami M, Abe Y. Preparation and mechanical properties of polylactic acid composites containing hydroxyapatite fibers. Biomaterials. 2001;22:19–23.

    Article  CAS  Google Scholar 

  4. Gay S, Arostegui S, Lemaitre J. Preparation and characterization of dense nanohydroxyapatite/PLLA composites. Mater Sci Eng C. 2009;29:172–7.

    Article  CAS  Google Scholar 

  5. Hong Z, Zhang P, He C, Qiu X, Liu A, Chen L, Chen X, Jing X. Nanocomposite of poly(l-lactide) and surface grafted hydroxyapatite: mechanical properties. Biomaterials. 2005;26:6296–304.

    Article  CAS  Google Scholar 

  6. Wang X, Song G, Lou T. Fabrication and characterization of nano composite scaffold of poly(L-lactic acid)/hydroxyapatite. J Mater Sci Mater Med. 2010;21:183–8.

    Article  CAS  Google Scholar 

  7. Huttunen M, Ashammakhi N, Törmälä P, Kellomäki M. Fibre reinforced bioresorbable composites for spinal surgery. Acta Biomater. 2006;2:575–87.

    Article  Google Scholar 

  8. Ignjatovic N, Delijic K, Vukcevic M, Uskokovic D. The designing of properties of hydroxyapatite/poly-l-lactide composite biomaterials by hot pressing. Z Metallkunde. 2001;92:145–9.

    CAS  Google Scholar 

  9. Rakovsky A, Gutmanas EY, Gotman I. Ca-deficient hydroxyapatite/polylactide nanocomposites with chemically modified interfaces by high pressure consolidation at room temperature. J Mater Sci. 2010;45:6339–44.

    Article  CAS  Google Scholar 

  10. Makarov C, Gotman I, Radin S, Ducheyne P, Gutmanas EY. Vancomycin release from bioresorbable calcium phosphate-polymer composites with high ceramic volume fractions. J Mater Sci. 2010;45:6320–4.

    Article  CAS  Google Scholar 

  11. Moriarty TF, Schlegel U, Perren S, Richards RG. Infection in fracture fixation: can we influence infection rates through implant design? J Mater Sci Mater Med. 2010;21:1031–5.

    Article  CAS  Google Scholar 

  12. Cyteval C, Bourdon A. Imaging orthopedic implant infections. Diagn Interv Imaging. 2012;93:547–57.

    Article  Google Scholar 

  13. Eglin D, Alini M. Degradable polymeric materials for osteosynthesis: tutorial. Eur Cell Mater. 2008;16:80–91.

    CAS  Google Scholar 

  14. Garvin K, Feschuk C. Polylactide–polyglycolide antibiotic implants. Clin Orhtop Rel Res. 2006;437:105–10.

    Google Scholar 

  15. Hetrick EM, Schoenfisch MH. Reducing implant-related infections: active release strategies. Chem Soc Rev. 2006;35:780–9.

    Article  CAS  Google Scholar 

  16. Wu P, Grainger DW. Drug/device combinations for local drug therapies and infection prophylaxis. Biomaterials. 2006;27:2450–67.

    Article  CAS  Google Scholar 

  17. Ashammakhi N, Veiranto M, Suokas E, Tiainen J, Niemelä SM, Törmälä P. Innovation in multifunctional bioabsorbable osteoconductive drug-releasing hard tissue fixation devices. J Mater Sci Mater Med. 2006;17:1275–82.

    Article  CAS  Google Scholar 

  18. Mäkinen TJ, Veiranto M, Knuuti J, Jalava J, Törmälä P, Aro HT. Efficacy of bioabsorbable antibiotic containing bone screw in the prevention of biomaterial-related infection due to Staphylococcus aureus. Bone. 2006;36:292–9.

    Article  Google Scholar 

  19. Russias J, Saiz E, Nalla RK, Gryn K, Ritchie RO, Tomsia AP. Fabrication and mechanical properties of PLA/HA composites: a study of in vitro degradation. Mat Sci Eng C. 2006;26:1289–95.

    Article  CAS  Google Scholar 

  20. Bernstein M, Makarov C, Gotman I, Phadke A, Radin S, Ducheyne P, Gutmanas EY. Low temperature fabrication of β-TCP–PCL nanocomposites for bone implants. Adv Eng Mater. 2010;12:B341–7.

    Article  Google Scholar 

  21. Winkler H, Janata O, Berger C, Wein W, Georgopoulus A. In vitro release of vancomycin and tobramycin from impregnated human and bovine bone grafts. J Antimicrob Chemoth. 2000;46:426–8.

    Article  Google Scholar 

  22. Gutmanas EY. Cold sintering-high pressure consolidation vol. 7 Powder metal technologies and applications. ASM Handbook. Materials Park: ASM International; 1998. p. 574–82.

    Google Scholar 

  23. Thomas M. In: Ando DJ, editor. Ultraviolet and visible spectroscopy, vol. 2. England: Wiley; 1996. p. 16.

    Google Scholar 

  24. Smith TL, Pearson LM, Wilcox KR, Cruz C, Lancaster MV, Robinson-Dunn B, Tenover FC, Zervos MJ, Band JD, White E, Jarvis WR. Emergence of vancomycin resistance in Staphylococcus aureus. N Engl J Med. 1999;340:493–501.

    Article  CAS  Google Scholar 

  25. Turner CH, Wang T, Burr DB. Shear strength and fatigue properties of human cortical bone determined from pure shear tests. Calcif Tissue Int. 2001;69:373–8.

    Article  CAS  Google Scholar 

  26. Currey JD. Mechanical properties of vertebrate hard tissues. Proc Inst Mech Eng H. 1998;212:341–99.

    Google Scholar 

  27. Makarov C. Bioresorbable calcium phosphate ceramic-polymer nanocomposites for load bearing bone healing devices–low temperature synthesis and drug incorporation. PhD thesis, Technion, Haifa, Israel; 2012.

  28. Russias J, Saiz E, Kikuchi M, Koyama Y, Takakuda K, Miyairi H, Shirahama N, Tanaka J. In vitro change in mechanical strength of β-tricalcium phosphate/copolymerized poly-l-lactide composites and their application for guided bone regeneration. J Biomed Mater Res. 2002;62:265–72.

    Article  Google Scholar 

  29. Weber C, Stephan R, Druggan P, Joosten H, Iversen C. Improving the enrichment procedure for enterobacteriaceae detection. Food Microbiol. 2009;26:565–72.

    Article  CAS  Google Scholar 

Download references

Acknowledgments

The financial support of German-Israeli foundation for scientific research and development (G.I.F), Grant No. 1092-28.2/2010 is gratefully acknowledged.

Author information

Authors and Affiliations

  1. Department of Materials Science and Engineering, Technion-Israel Institute of Technology, 32000, Haifa, Israel

    C. Makarov & I. Gotman

  2. Department of Microbiology, Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, 31096, Haifa, Israel

    I. Berdicevsky & A. Raz-Pasteur

Authors
  1. C. Makarov
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. I. Berdicevsky
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. A. Raz-Pasteur
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. I. Gotman
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to I. Gotman.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Makarov, C., Berdicevsky, I., Raz-Pasteur, A. et al. In vitro antimicrobial activity of vancomycin-eluting bioresorbable β-TCP-polylactic acid nanocomposite material for load-bearing bone repair. J Mater Sci: Mater Med 24, 679–687 (2013). https://doi.org/10.1007/s10856-012-4832-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10856-012-4832-y

Keywords

Search

Navigation