Skip to main content

Preparation of graphene oxide-reinforced calcium phosphate/calcium sulfate/methylcellulose-based injectable bone substitutes

Abstract

In this study, an injectable bone substitute (IBS) was produced by mixing a liquid and powder phase. The liquid phase consisted of 8 wt% methylcellulose (MC), 2.5% gelatin, and different amounts of graphene oxide (GO). The powder phase was composed of tetracalcium phosphate (TTCP), dicalcium phosphate dihydrate (DCPD), and calcium sulfate dihydrate (CSD). The results showed that 1 and 1.5 wt% GO added IBS samples showed higher stability, injectability, rheological properties, and biocompatibility than the other GO added IBS samples. GO addition significantly decreased the setting time, but it did not significantly affect the compressive strength of the samples.

This is a preview of subscription content, access via your institution.

Figure 1.
Figure 2.
Figure 3.
Figure 4.

References

  1. 1.

    Z. Chen, X. Zhang, L. Kang, F. Xu, Z. Wang, F.Z. Cui, and Z. Guo: Recent progress in injectable bone repair materials research. Front. Mater. Sci. 9, 332(2015).

    Article  Google Scholar 

  2. 2.

    S. Larsson and T.W. Bauer Use of injectable calcium phosphate cement for fracture fixation: a review. Clin. Orthop. Relat. Res. 395, 23–32 (2002).

    Article  Google Scholar 

  3. 3.

    W.E. Brown and L.C. Chow: A new calcium phosphate setting cement. J. Dent. Res. 62, 672(1983).

    Google Scholar 

  4. 4.

    M. Smiga-Matuszowicz, J. Tukaszczyk, R. Pilawka, M. Basiaga, M. Bilewicz, and D. Kusz: Novel crosslinkable polyester resin-based composites as injectable bioactive scaffolds. Int. J. Polym. Mater. Polym. Biomater. 66, 1–11 (2017).

    CAS  Article  Google Scholar 

  5. 5.

    S. Sharifi, M. Imani, H. Mirzadeh, M. Atai, F. Ziaee, and R. Bakhshi: Synthesis, characterization, and biocompatibility of novel injectable, biodegradable, and in situ crosslinkable polycarbonate-based macromers. J. Biomed. Mater. Res. A 90, 830–843 (2009).

    Article  Google Scholar 

  6. 6.

    V.V. Thai and B.T. Lee: Fabrication of calcium phosphate-calcium sulfate injectable bone substitute using hydroxy-propyl-methyl-cellulose and citric acid. J. Mater. Sci. Mater. Med. 21, 1867–1874 (2010).

    CAS  Article  Google Scholar 

  7. 7.

    M.P. Ginebra, T. Traykova, and J.A. Planell: Calcium phosphate cements as bone drug delivery systems: a review. J. Control. Release 113, 102–110 (2006).

    CAS  Article  Google Scholar 

  8. 8.

    H. Liu, H. Li, W. Cheng, Y. Yang, M. Zhu, and C. Zhou: Novel injectable calcium phosphate/chitosan composites for bone substitute materials. Acta Biomater. 2, 557–565 (2006).

    Article  Google Scholar 

  9. 9.

    M.V. Priya, A. Sivshanmugam, A.R. Boccaccini, O.M. Goudouri, W. Sun, N. Hwang, S. Deepthi, S.V. Nair, and R. Jayakumar: Injectable osteogenic and angiogenic nanocomposite hydrogels for irregular bone defects Injectable osteogenic and angiogenic nanocomposite hydrogels for irregular bone defects. Biomed. Mater. 11, 035017 (2016).

    Article  Google Scholar 

  10. 10.

    R. O’Neill, H.O. McCarthy, E.B. Montufar, M.-P. Ginebra, D.I. Wilson, A. Lennon, and N. Dunne: Critical review: injectability of calcium phosphate pastes and cements. Acta Biomater. 50, 1–19 (2017).

    Article  Google Scholar 

  11. 11.

    S. Ghanaati, M. Barbeck, U. Hilbig, C. Hoffmann, R.E. Unger, R.A. Sader, F. Peters, and C.J. Kirkpatrick: An injectable bone substitute composed of beta-tricalcium phosphate granules, methylcellulose and hyaluronic acid inhibits connective tissue influx into its implantation bed in vivo. Acta Biomater. 7, 4018–4028 (2011).

    CAS  Article  Google Scholar 

  12. 12.

    M. Krause, R. Oheim, P. Catala-Lehnen, J.M. Pestka, C. Hoffmann, W. Huebner, F. Peters, F. Barvencik, and M. Amling: Metaphyseal bone formation induced by a new injectable beta-TCP-based bone substitute: a controlled study in rabbits. J. Biomater. Appl. 28, 859–868 (2014).

    Article  Google Scholar 

  13. 13.

    H. Wang, S.C.G. Leeuwenburgh, Y. Li, and J.A. Jansen: The use of micro-and nanospheres as functional components for bone tissue regeneration. Tissue Eng. Part B Rev. 18, 24–39 (2012).

    Article  Google Scholar 

  14. 14.

    M. Dessi, M.A. Alvarez-Perez, R. De Santis, M.P. Ginebra, J.A. Planell, and L. Ambrosio: Bioactivation of calcium deficient hydroxyapatite with foamed gelatin gel. A new injectable self-setting bone analogue. J. Mater. Sci. Mater. Med. 25, 283–295 (2014).

    CAS  Article  Google Scholar 

  15. 15.

    M. Bongio, M.R. Nejadnik, F.K. Kasper, A.G. Mikos, J.A. Jansen, S.C.G. Leeuwenburgh, and J.J.J.P. van den Beucken: Development of an in vitro confinement test to predict the clinical handling of polymer-based injectable bone substitutes. Polym. Test. 32, 1379–1384 (2013).

    CAS  Article  Google Scholar 

  16. 16.

    D. Ege, A.R. Kamali, and A.R. Boccaccini: Graphene oxide/polymer-based biomaterials. Adv. Eng. Mater. 19, 1700627 (2017).

    Article  Google Scholar 

  17. 17.

    C. Baudín, T. Benet, and P. Pena: Effect of graphene on setting and mechanical behaviour of tricalcium phosphate bioactive cements. J. Mech. Behav. Biomed. Mater. 89, 33–47 (2019).

    Article  Google Scholar 

  18. 18.

    X. Zhenkun, Y. Haoran, W. Tao, W. Ruizhen, P. Zhang, L. Xiaoying, and W. Jie: Effects of adding reduced-graphene oxide/polypyrrole composites on the structure and properties of calcium phosphate cement. Chem. J. Chinese Univ. 36, 2598–2603 (2015).

    Google Scholar 

  19. 19.

    C. Wu, L. Xia, P. Han, M. Xu, B. Fang, J. Wang, J. Chang, and Y. Xiao: Graphene-oxide-modified β-tricalcium phosphate bioceramics stimulate in vitro and in vivo osteogenesis. Carbon 93, 116–129 (2015).

    CAS  Article  Google Scholar 

  20. 20.

    C. Gao, P. Feng, S. Peng, and C. Shuai: Carbon nanotube, graphene and boron nitride nanotube reinforced bioactive ceramics for bone repair. Acta Biomater. 61, 1–20 (2017).

    CAS  Article  Google Scholar 

  21. 21.

    Ö.D. Oguz and D. Ege: Rheological and mechanical properties of thermor-esponsive methylcellulose/calcium phosphate-based injectable bone substitutes. Materials 11, 604 (2018).

    Article  Google Scholar 

  22. 22.

    S. Wang, S. Zhang, Y. Wang, X. Sun, and K. Sun: Reduced graphene oxide/carbon nanotubes reinforced calcium phosphate cement. Ceram. Int. 43, 13083–13088 (2017).

    CAS  Article  Google Scholar 

  23. 23.

    V. Campana, G. Milano, E. Pagano, M. Barba, C. Cicione, G. Salonna, W. Lattanzi, and G. Logroscino: Bone substitutes in orthopaedic surgery: from basic science to clinical practice. J. Mater. Sci. Mater. Med. 25, 244–2461 (2014).

    Article  Google Scholar 

  24. 24.

    S. Lian, Y. Xiao, Q. Bian, Y. Xia, C. Guo, S. Wang, and M. Lang: Injectable hydrogel as stem cell scaffolds from the thermosensitive terpolymer of NIPAAm/AAc/HEMAPCL. Int. J. Nanomedicine 7, 4893–4905 (2012).

    CAS  Google Scholar 

  25. 25.

    N. Nasrollahi, A.N. Dehkordi, A. Jamshidizad, and M. Chehelgerdi: Preparation of brushite cements with improved properties by adding graphene oxide. Int. J. Nanomedicine 14, 378–3797 (2019).

    Article  Google Scholar 

  26. 26.

    Z. Liu and P. Yao: Injectable thermo-responsive hydrogel composed of xanthan gum and methylcellulose double networks with shear-thinning property. Carbohydr. Polym. 132, 490–498 (2015).

    CAS  Article  Google Scholar 

  27. 27.

    T.Y. Chiang, C.C. Ho, D.C.H. Chen, M.H. Lai, and S.J. Ding: Physicochemical properties and biocompatibility of chitosan oligosaccha-ride/gelatin/calcium phosphate hybrid cements. Mater. Chem. Phys. 120, 282–288 (2010).

    CAS  Article  Google Scholar 

  28. 28.

    J. Liu, Q. Li, and S. Xu: Reinforcing mechanism of graphene and gra-phene oxide sheets on cement-based materials. J. Mater. Civ. Eng. 31, 04019014 (2019).

    CAS  Article  Google Scholar 

  29. 29.

    B. von Lospichl, S. Hemmati-Sadeghi, P. Dey, T. Dehne, R. Haag, M. Sittinger, J. Ringe, and M. Gradzielski: Biointerfaces Injectable hydrogels for treatment of osteoarthritis–a rheological study. Colloids Surf. B 159, 477–483 (2017).

    Article  Google Scholar 

  30. 30.

    C.E. Misch, Z. Qu, and M.W. Bidez: Mechanical properties of trabecular bone in the human mandible: Implications for dental implant treatment planning and surgical placement. J. Oral Maxillofac. Surg. 57, 700–706 (1999).

    CAS  Article  Google Scholar 

  31. 31.

    S. Prasadh, S. Suresh, and R. Wong: Osteogenic potential of graphene in bone tissue engineering scaffolds. Materials 11, 1430 (2018).

    Article  Google Scholar 

  32. 32.

    S. Gurunathan, M.-H. Kang, M. Jeyaraj, and J.H. Kim: Differential cytotox-icity of different sizes of graphene oxide nanoparticles in leydig (TM3) and sertoli (TM4) cells. Nanomaterials 9, 139 (2019).

    CAS  Article  Google Scholar 

Download references

Acknowledgment

This work was supported by Boğaziçi University Research fund (No. 12240) and the Scientific and Technological Research Council of Turkey (TUBITAK) (No. 117M231).

Author information

Affiliations

Authors

Corresponding author

Correspondence to Duygu Ege.

Supplementary material

Supplementary material

The supplementary material for this article can be found at https://doi.org/10.1557/mrc.2019.125.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Oğuz, Ö.D., Ege, D. Preparation of graphene oxide-reinforced calcium phosphate/calcium sulfate/methylcellulose-based injectable bone substitutes. MRS Communications 9, 1174–1180 (2019). https://doi.org/10.1557/mrc.2019.125

Download citation