Skip to main content
SpringerLink
Log in

Characterization of Polymeric Solutions as Injectable Vehicles for Hydroxyapatite Microspheres

  • Research Article
  • Published:
AAPS PharmSciTech Aims and scope Submit manuscript

Abstract

A polymeric solution and a reinforcement phase can work as an injectable material to fill up bone defects. However, the properties of the solution should be suitable to enable the transport of that extra phase. Additionally, the use of biocompatible materials is a requirement for tissue regeneration. Thus, we intended to optimize a biocompatible polymeric solution able to carry hydroxyapatite microspheres into bone defects using an orthopedic injectable device. To achieve that goal, polymers usually regarded as biocompatible were selected, namely sodium carboxymethylcellulose, hydroxypropylmethylcellulose, and Na-alginate (ALG). The rheological properties of the polymeric solutions at different concentrations were assessed by viscosimetry before and after moist heat sterilization. In order to correlate rheological properties with injectability, solutions were tested using an orthopedic device applied for minimal invasive surgeries. Among the three polymers, ALG solutions presented the most suitable properties for our goal and a non-sterile ALG 6% solution was successfully used to perform preliminary injection tests of hydroxyapatite microspheres. Sterile ALG 7.25% solution was found to closely match non-sterile ALG 6% properties and it was selected as the optimal vehicle. Finally, sterile ALG 7.25% physical stability was studied at different temperatures over a 3-month period. It was observed that its rheological properties presented minor changes when stored at 25°C or at 4°C.

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. Verlaan JJ, Oner FC, Dhert WJ. Anterior spinal column augmentation with injectable bone cements. Biomat. 2006;27(3):290–301.

    Article  CAS  Google Scholar 

  2. Chenite A, Chaput C, Wang D, Combes C, Buschmann MD, Hoemann CD, et al. Novel injectable neutral solutions of chitosan form biodegradable gels in situ. Biomat. 2000;21(21):2155–61.

    Article  CAS  Google Scholar 

  3. Hoemann CD, Sun J, Legare A, McKee MD, Buschmann MD. Tissue engineering of cartilage using an injectable and adhesive chitosan-based cell-delivery vehicle. Osteoarthritis Cart. 2005;13(4):318–29.

    Article  CAS  Google Scholar 

  4. Balakrishnan B, Jayakrishnan A. Self-cross-linking biopolymers as injectable in situ forming biodegradable scaffolds. Biomat. 2005;26(18):3941–51.

    Article  CAS  Google Scholar 

  5. Shu XZ, Ghosh K, Liu Y, Palumbo FS, Luo Y, Clark RA, et al. Attachment and spreading of fibroblasts on an RGD peptide-modified injectable hyaluronan hydrogel. J Biomed Mater Res. 2004;68A(2):365–75.

    Article  CAS  Google Scholar 

  6. Shu XZ, Ahmad S, Liu Y, Prestwich GD. Synthesis and evaluation of injectable, in situ crosslinkable synthetic extracellular matrices for tissue engineering. J Biomed Mater Res A. 2006;79(4):902–12.

    PubMed  Google Scholar 

  7. Weiss P, Gauthier O, Bouler JM, Grimandi G, Daculsi G. Injectable bone substitute using a hydrophilic polymer. Bone. 1999;25(2 Suppl):67S–70S.

    Article  CAS  PubMed  Google Scholar 

  8. Trojani C, Weiss P, Michiels JF, Vinatier C, Guicheux J, Daculsi G, et al. Three-dimensional culture and differentiation of human osteogenic cells in an injectable hydroxypropylmethylcellulose hydrogel. Biomat. 2005;26(27):5509–17.

    Article  CAS  Google Scholar 

  9. Virto MR, Frutos P, Torrado S, Frutos G. Gentamicin release from modified acrylic bone cements with lactose and hydroxypropylmethylcellulose. Biomat. 2003;24(1):79–87.

    Article  CAS  Google Scholar 

  10. Bodic F, Amouriq Y, Gayet-Delacroix M, Gauthier O, Bouler J-M, Daculsi G, et al. Méthode nom invasive d'evaluation d'un substitut osseux injectable/Non-invasive evaluation of an injectable bone substitute. C R Biologies. 2002;325:345–53.

    Article  PubMed  Google Scholar 

  11. Andrews GP, Gorman SP, Jones DS. Rheological characterisation of primary and binary interactive bioadhesive gels composed of cellulose derivatives designed as ophthalmic viscosurgical devices. Biomat. 2005;26(5):571–80.

    Article  CAS  Google Scholar 

  12. He S, Yaszemski MJ, Yasko AW, Engel PS, Mikos AG. Injectable biodegradable polymer composites based on poly(propylene fumarate) crosslinked with poly(ethylene glycol)-dimethacrylate. Biomat. 2000;21(23):2389–94.

    Article  CAS  Google Scholar 

  13. Temenoff JS, Mikos AG. Injectable biodegradable materials for orthopedic tissue engineering. Biomat. 2000;21(23):2405–12.

    Article  CAS  Google Scholar 

  14. Iooss P, Le Ray AM, Grimandi G, Daculsi G, Merle C. A new injectable bone substitute combining poly(epsilon-caprolactone) microparticles with biphasic calcium phosphate granules. Biomat. 2001;22(20):2785–94.

    Article  CAS  Google Scholar 

  15. Uda H, Sugawara Y, Nakasu M. Experimental studies on hydroxyapatite powder-carboxymethyl chitin composite: injectable material for bone augmentation. J Plast Reconstr Aesthet Surg. 2006;59(2):188–96.

    Article  PubMed  Google Scholar 

  16. Carrodeguas RG, Lasa BV, Del Barrio JS. Injectable acrylic bone cements for vertebroplasty with improved properties. J Biomed Mater Res B-Appl Biomat. 2004;68(1):94–104.

    Article  Google Scholar 

  17. Oliveira SM, Barrias CC, Ribeiro CC, Almeida IF, Bahia MF, Barbosa MA. Morphology and mechanical properties of injectable ceramic microspheres. Key Engineering Mat. 2009;396–398:691–4.

    Article  Google Scholar 

  18. Barrias CC, Ribeiro CC, Barbosa MA. Adhesion and proliferation of human osteoblastic cells seeded on injectable hydroxyapatite microspheres. Key Engineering Mat. 2004;254–256:877–80.

    Article  Google Scholar 

  19. Ribeiro CC, Barrias CC, Barbosa MA. Preparation and characterisation of calcium-phosphate porous microspheres with a uniform size for biomedical applications. J Mater Sci Mater Med. 2006;17(5):455–63.

    Article  CAS  PubMed  Google Scholar 

  20. Oliveira SM, Barrias CC, Almeida IF, Costa PC, Ferreira MP, Bahia MF, et al. Injectability of a bone filler system based on hydroxyapatite microspheres and a vehicle with in situ gel-forming ability. J Biomed Mater Res B-Appl Biomat. 2008;87B:49–58.

    Article  CAS  Google Scholar 

  21. Barnes HA, Hutton JF, Walters K. An introduction to rheology. Amsterdam: Elsevier Science; 1998.

    Google Scholar 

  22. Leo WJ, McLoughlin AJ, Malone DM. Effects of sterilization treatments on some properties of alginate solutions and gels. Biotech Progress. 1990;6(1):51–3.

    Article  CAS  Google Scholar 

  23. Holme HK, Lindmo K, Kristiansen A, Smidsrød O. Thermal depolymerization of alginate in the solid state. Carbohydrate Polym. 2003;54(4):431–8.

    Article  CAS  Google Scholar 

  24. Bohner M, Baroud G. Injectability of calcium phosphate pastes. Biomat. 2005;26(13):1553–63.

    Article  CAS  Google Scholar 

  25. Hide IG, Gangi A. Percutaneous vertebroplasty: history, technique and current perspectives. Clin Radiol. 2004;59(6):461–7.

    Article  CAS  PubMed  Google Scholar 

  26. Lewis G. Injectable bone cements for use in vertebroplasty and kyphoplasty: state-of-the-art review. J Biomed Mat Res B-Appl Biomat. 2006;76B(2):456–68.

    Article  CAS  Google Scholar 

  27. Baumann A, Tauss J, Baumann G, Tomka M, Hessinger M, Tiesenhausen K. Cement embolization into the vena cava and pulmonal arteries after vertebroplasty: interdisciplinary management. Europ J Vasc and End Surg. 2006;31(5):558–61.

    Article  CAS  Google Scholar 

  28. Mathis JM, Wong W. Percutaneous vertebroplasty: technical considerations. J Vasc and Intervent Rad. 2003;14(8):953–60.

    Google Scholar 

  29. Xu HH, Weir MD, Burguera EF, Fraser AM. Injectable and macroporous calcium phosphate cement scaffold. Biomat. 2006;27(24):4279–87.

    Article  CAS  Google Scholar 

  30. Gisep A, Curtis R, Hanni M, Suhm N. Augmentation of implant purchase with bone cements: an in vitro study of injectability and dough distribution. J Biomed Mater Res B-Appl Biomat. 2006;77(1):114–9.

    Article  CAS  Google Scholar 

  31. Krebs J, Ferguson SJ, Bohner M, Baroud G, Steffen T, Heini PF. Clinical measurements of cement injection pressure during vertebroplasty. Spine. 2005;30(5):E118–22.

    Article  PubMed  Google Scholar 

  32. Draget KI, Skjak-Braek G, Smidsrod O. Alginate-based new materials. Int J Biol Macromol. 1997;21(1–2):47–55.

    Article  CAS  PubMed  Google Scholar 

Download references

ACKNOWLEDGMENTS

SM Oliveira is grateful to the Program for Education Development in Portugal III (PRODEP III) for supporting his salary at Escola Superior de Tecnologia de Viseu, Portugal. This work was supported by Foundation for Science and Technology (FCT) under contract POCTI/FCB/41523/2001.

Author information

Authors and Affiliations

  1. Dep. de Eng. Mecânica e Gestão Industrial, Escola Superior de Tecnologia e Gestão de Viseu, Campus Politécnico de Repeses, 3504-510, Viseu, Portugal

    Serafim M. Oliveira

  2. Divisão de biomateriais, Instituto de Engenharia Biomédica, 4150-180, Porto, Portugal

    Serafim M. Oliveira, Cristina C. Barrias & Mário A. Barbosa

  3. Dep. de Eng. Metalúrgica e de Materiais, Faculdade de Engenharia Universidade do Porto, 4200-465, Porto, Portugal

    Mário A. Barbosa

  4. Departamento de Tecnologia Farmacêutica, Faculdade de Farmácia da Universidade do Porto, 4050-047, Porto, Portugal

    Isabel F. Almeida, Paulo C. Costa, M. Rosa Pena Ferreira & M. Fernanda Bahia

Authors
  1. Serafim M. Oliveira
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Isabel F. Almeida
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Paulo C. Costa
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Cristina C. Barrias
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. M. Rosa Pena Ferreira
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. M. Fernanda Bahia
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Mário A. Barbosa
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Serafim M. Oliveira.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Oliveira, S.M., Almeida, I.F., Costa, P.C. et al. Characterization of Polymeric Solutions as Injectable Vehicles for Hydroxyapatite Microspheres. AAPS PharmSciTech 11, 852–858 (2010). https://doi.org/10.1208/s12249-010-9447-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1208/s12249-010-9447-3

Key words

Search

Navigation