Skip to main content
SpringerLink
Log in

Tetracycline-encapsulated P(3HB) microsphere-coated 45S5 Bioglass®-based scaffolds for bone tissue engineering

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

Abstract

Bioglass®-based scaffolds for bone tissue engineering have been developed, which can also serve as carriers for drug delivery. For this, P(3HB) microspheres (PMSs) loaded with tetracycline were fabricated and immobilised on the scaffold surfaces by a modified slurry dipping technique. The sustained drug delivery ability in simulated body fluid was confirmed by using UV–Vis absorption spectroscopy measurements. The MTT assay using mouse fibroblast cells provided evidence that the tetracycline loaded microspheres produced in this study show limited cytotoxicity. The scaffolds developed in this work provide mechanical support, adequate 3D surface roughness, bioactivity and controlled drug delivery function, and are thus interesting candidates for bone tissue engineering applications.

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

Similar content being viewed by others

References

  1. Chen QZ, Thompson ID, Boccaccini AR. 45S5 Bioglass (R)-derived glass–ceramic scaffolds for bone tissue engineering. Biomaterials. 2006;27:2414–25.

    Article  CAS  Google Scholar 

  2. Bretcanu O, Misra S, Roy I, Renghini C, Fiori F, Boccaccini AR, Salih V. In vitro biocompatibility of 45S5 Bioglass (R)-derived glass–ceramic scaffolds coated with poly(3-hydroxybutyrate). J Tissue Eng Regen Med. 2009;3:139–48.

    Article  CAS  Google Scholar 

  3. Chen QZ, Efthymiou A, Salih V, Boccaccinil AR. Bioglass (R)-derived glass-ceramic scaffolds: study of cell proliferation and scaffold degradation in vitro. J Biomed Mater Res Part A. 2008;84A:1049–60.

    Article  CAS  Google Scholar 

  4. Xynos ID, Edgar AJ, Buttery LDK, Hench LL, Polak JM. Gene-expression profiling of human osteoblasts following treatment with the ionic products of Bioglass (R) 45S5 dissolution. J Biomed Mater Res. 2001;55:151–7.

    Article  CAS  Google Scholar 

  5. Hench LL. Genetic design of bioactive glass. J Eur Ceram Soc. 2009;29:1257–65.

    Article  CAS  Google Scholar 

  6. Gorustovich AA, Roether JA, Boccaccini AR. Effect of bioactive glasses on angiogenesis: a review of in vitro and in vivo evidences. Tissue Eng Part B. 2010;16:199–207.

    Article  CAS  Google Scholar 

  7. Hoppe A, Güldal NS, Boccaccini AR. A review of the biological response to ionic dissolution products from bioactive glasses and glass–ceramics. Biomaterials. 2011;32:2757–74.

    Article  CAS  Google Scholar 

  8. Soundrapandian C, Sa B, Datta S. Organic–inorganic composites for bone drug delivery. AAPS PharmSciTech. 2009;10:1158–71.

    Article  CAS  Google Scholar 

  9. Lee SH, Shin H. Matrices and scaffolds for delivery of bioactive molecules in bone and cartilage tissue engineering. Adv Drug Deliv Rev. 2007;59:339–59.

    Article  CAS  Google Scholar 

  10. Mourino V, Boccaccini AR. Bone tissue engineering therapeutics: controlled drug delivery in three-dimensional scaffolds. J R Soc Interface. 2010;7:209–27.

    Article  CAS  Google Scholar 

  11. Vo TN, Kasper FK, Mikos AG. Strategies for controlled delivery of growth factors and cells for bone regeneration. Adv Drug Deliv Rev. 2012;64(12):1292–309.

    Article  CAS  Google Scholar 

  12. Baroli B. From natural bone grafts to tissue engineering therapeutics: brainstorming on pharmaceutical formulative requirements and challenges. J Pharm Sci. 2009;98:1317–75.

    Article  CAS  Google Scholar 

  13. Domingues ZR, Cortes ME, Gomes TA, Diniz HF, Freitas CS, Gomes JB, Faria AMC, Sinisterra RD. Bioactive glass as a drug delivery system of tetracycline and tetracycline associated with beta cyclodextrin. Biomaterials. 2004;25:327–33.

    Article  CAS  Google Scholar 

  14. Kim HW, Knowles JC, Kim HE. Development of hydroxyapatite bone scaffold for controlled drug release via poly(epsilon-caprolactone) and hydroxyapatite hybrid coatings. J Biomed Mater Res. 2004;70B:240–9.

    Article  CAS  Google Scholar 

  15. Roohani-Esfahani S-I, Lu Z, Zreiqat H. Novel, simple and reproducible method for preparation of composite hierarchal porous structure scaffolds. Mater Lett. 2011;65:2578–81.

    Article  CAS  Google Scholar 

  16. Yun H, Kim S-H, Khang D, Choi J, Kim H, Kang M. Biomimetic component coating on 3D scaffolds using high bioactivity of mesoporous bioactive ceramics. Int J Nanomed. 2011;6:2521–31.

    Article  CAS  Google Scholar 

  17. Yunos DM, Bretcanu O, Boccaccini AR. Polymer-bioceramic composites for tissue engineering scaffolds. J Mater Sci. 2008;43:4433–42.

    Article  Google Scholar 

  18. Yang G, Yang X, Zhang L, Lin M, Sun X, Chen X, Gou X. Counterionic biopolymers-reinforced bioactive glass scaffolds with improved mechanical properties in wet state. Mater Lett. 2012;75:80–3.

    Article  CAS  Google Scholar 

  19. Francis L, Meng DC, Knowles JC, Roy I, Boccaccini AR. Multi-functional P(3HB) microsphere/45S5 Bioglass (R)-based composite scaffolds for bone tissue engineering. Acta Biomater. 2010;6:2773–86.

    Article  CAS  Google Scholar 

  20. Roohani-Esfahani SI, Nouri-Khorasani S, Lu ZF, Appleyard RC, Zreiqat H. Effects of bioactive glass nanoparticles on the mechanical and biological behavior of composite coated scaffolds. Acta Biomater. 2011;7:1307–18.

    Article  CAS  Google Scholar 

  21. Wu C, Fan W, Chang J, Xiao Y. Mussel-inspired SiO2 scaffolds with improved mineralization and cytocompatibility for drug delivery and bone tissue engineering. J Mater Chem. 2011;21:18300–7.

    Article  CAS  Google Scholar 

  22. Erol MM, Mouriňo V, Newby P, Chatzistavrou X, Roether JA, Hupa L, Boccaccini AR. Copper releasing boron containing bioactive glass-based scaffolds coated with alginate for bone tissue engineering. Acta Biomater. 2012;8:792–801.

    Article  CAS  Google Scholar 

  23. Corre Y-M, Bruzaud S, Audic J-L, Grohens Y. Morphology and functional properties of commercial polyhydroxyalkanoates: a comprehensive and comparative study. Polym Testing. 2012;31:226–35.

    Article  CAS  Google Scholar 

  24. Misra SK, Valappil SP, Roy I, Boccaccini AR. Polyhydroxyalkanoate (PHA)/inorganic phase composites for tissue engineering applications. Biomacromolecules. 2006;7:2249–58.

    Article  CAS  Google Scholar 

  25. Hayati AM, Hosseinalipour SM, Rezaie HR, Shokrgozar MA. Characterization of poly(3-hydroxybutyrate)/nano-hydroxyapatite composite scaffolds fabricated without the use of organic solvents for bone tissue engineering applications. Mater Sci Eng C. 2012;32:416–22.

    Article  Google Scholar 

  26. Pouton CW, Akhtar S. Biosynthetic polyhydroxyalkanoates and their potential in drug delivery. Adv Drug Deliv Rev. 1996;18:133–62.

    Article  CAS  Google Scholar 

  27. Foroughi MR, Karbasi S, Ebrahimi-Kahrizsangi R. Physical and mechanical properties of a poly-3-hydroxybutyrate-coated nanocrystalline hydroxyapatite scaffold for bone tissue engineering. J Porous Mater. 2012;. doi:10.1007/s10934-011-9518-1.

    Google Scholar 

  28. Embleton JK, Tighe BJ. Polymers for biodegradable medical devices.9. microencapsulation studies - effects of polymer composition and process parameters on poly-hydroxybutyrate hydroxyvalerate microcapsule morphology. J Microencapsul. 1992;9:73–87.

    Article  CAS  Google Scholar 

  29. Francis L, Meng D, Knowles J, Keshavarz T, Boccaccini AR, Roy I. Controlled delivery of gentamicin using poly(3-hydroxybutyrate) microspheres. Int J Mol Sci. 2011;12:4294–314.

    Article  CAS  Google Scholar 

  30. Zolnik BS, Burgess DJ. Effect of acidic pH on PLGA microsphere degradation and release. J Control Release. 2007;122:338–44.

    Article  CAS  Google Scholar 

  31. Valappil SP, Misra SK, Boccaccini AR, Keshavarz T, Bucke C, Roy I. Large scale production and efficient recovery of PHB with desirable material properties, from the newly characterised Bacillus cereus SPV. J Biotechnol. 2007;132:251–8.

    Article  CAS  Google Scholar 

  32. Meng D, Ioannou J, Boccaccini AR. Bioglass-based scaffolds with carbon nanotube coating for bone tissue engineering. J Mater Sci Mater Med. 2009;20:2139–44.

    Article  CAS  Google Scholar 

  33. Tanahashi M, Yao T, Kokubo T, Minoda M, Miyamato T, Nakamura T, Yamamuro T. Apatite coating on organic polymers by a biomimetic precess. J Am Ceram Soc. 1994;77:2805.

    Article  CAS  Google Scholar 

  34. Medvecky L, Stulajterova R, Briancin J. Study of controlled tetracycline release from porous calcium phosphate/polyhydroxybutyrate composites. Chem Pap. 2007;61:477–84.

    Article  CAS  Google Scholar 

  35. Ratier A, Freche M, Lacout JL, Rodriguez F. Behaviour of an injectable calcium phosphate cement with added tetracycline. Int J Pharm. 2004;274:261–8.

    Article  CAS  Google Scholar 

  36. Ratier A, Gibson IR, Best SM, Freche M, Lacout JL, Rodriguez F. Setting characteristics and mechanical behaviour of a calcium phosphate bone cement containing tetracycline. Biomaterials. 2001;22:897–901.

    Article  CAS  Google Scholar 

  37. Tongaree S, Flanagan DR, Poust RI. The interaction between oxytetracycline and divalent metal ions in aqueous and mixed solvent systems. Pharm Dev Technol. 1999;4:581–91.

    Article  CAS  Google Scholar 

  38. Gbureck U, Vorndran E, Muller FA, Barralet JE. Low temperature direct 3D printed bioceramics and biocomposites as drug release matrices. J Control Release. 2007;122:173–80.

    Article  CAS  Google Scholar 

  39. Wenke JC, Guelcher SA. Dual delivery of an antibiotic and a growth factor addresses both the microbiological and biological challenges of contaminated bone fractures. Expert Opin Drug Deliv. 2011;8:1555–69.

    Article  CAS  Google Scholar 

  40. Kimakhe S, Bohic S, Larosse C, Reynaud A, Pilet P, Giumelli B, Heymann D, Daculsi G. Biological activities of sustained polymixin B release from calcium phosphate biomaterial prepared by dynamic compaction: an in vitro study. J Biomed Mater Res. 1999;47:18–27.

    Article  CAS  Google Scholar 

  41. Vallet-Regí M, Ruiz-González L, Izquierdo-Barba I, González-Calbet J. Revisiting silica based ordered mesoporous materials: medical applications. J Mater Chem. 2006;16:26–31.

    Article  Google Scholar 

  42. Wu C, Miron R, Sculean A, Kaskel S, Doert T, Schulze R, Zhang Y. Proliferation, differentiation and gene expression of osteoblasts in boron-containing associated with dexamethasone deliver from mesoporous bioactive glass scaffolds. Biomaterials. 2011;32:7068–78.

    Article  CAS  Google Scholar 

  43. Mortera R, Onida B, Fiorilli S, Cauda V, Vitale-Brovarone C, Baino F, Verné E, Garrone E. Synthesis and characterization of MCM-41 spheres inside bioactive glass–ceramic scaffold. Chem Eng J. 2007;137:54–61.

    Article  Google Scholar 

Download references

Author information

Author notes

  1. C. Mierke

    Present address: Soft Matter Physics Division, Faculty of Physics and Earth Science, University of Leipzig, 04103, Leipzig, Germany

Authors and Affiliations

  1. Department of Materials, Imperial College London, London, SW7 2BP, UK

    D. Meng & A. R. Boccaccini

  2. Department of Molecular and Applied Biology, University of Westminster, London, W1W 6UW, UK

    L. Francis & I. Roy

  3. Biomaterials Unit, Dental Institute, King’s College London, London, SE1 9RT, UK

    I. D. Thompson

  4. Biophysics Group, University of Erlangen-Nuremberg, 91052, Erlangen, Germany

    C. Mierke

  5. Institute of Bioprocess Engineering, University of Erlangen-Nuremberg, 91052, Erlangen, Germany

    H. Huebner & A. Amtmann

  6. Institute of Biomaterials, University of Erlangen-Nuremberg, 91058, Erlangen, Germany

    A. R. Boccaccini

Authors
  1. D. Meng
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. L. Francis
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. I. D. Thompson
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. C. Mierke
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. H. Huebner
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. A. Amtmann
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. I. Roy
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. A. R. Boccaccini
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to A. R. Boccaccini.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Meng, D., Francis, L., Thompson, I.D. et al. Tetracycline-encapsulated P(3HB) microsphere-coated 45S5 Bioglass®-based scaffolds for bone tissue engineering. J Mater Sci: Mater Med 24, 2809–2817 (2013). https://doi.org/10.1007/s10856-013-5012-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10856-013-5012-4

Keywords

Search

Navigation