Skip to main content
SpringerLink
Log in

Carbon Nanotube–Poly(lactide-co-glycolide) Composite Scaffolds for Bone Tissue Engineering Applications

  • Published:
Annals of Biomedical Engineering Aims and scope Submit manuscript

Abstract

Despite their indisputable clinical value, current tissue engineering strategies face major challenges in recapitulating the natural nano-structural and morphological features of native bone. The aim of this study is to take a step forward by developing a porous scaffold with appropriate mechanical strength and controllable surface roughness for bone repair. This was accomplished by homogenous dispersion of carbon nanotubes (CNTs) in a poly(lactide-co-glycolide) (PLGA) solution followed by a solvent casting/particulate leaching scaffold fabrication. Our results demonstrated that CNT/PLGA composite scaffolds possessed a significantly higher mechanical strength as compared to PLGA scaffolds. The incorporation of CNTs led to an enhanced surface roughness and resulted in an increase in the attachment and proliferation of MC3T3-E1 osteoblasts. Most interestingly, the in vitro osteogenesis studies demonstrated a significantly higher rate of differentiation on CNT/PLGA scaffolds compared to the control PLGA group. These results all together demonstrate the potential of CNT/PLGA scaffolds for bone tissue engineering as they possess the combined effects of mechanical strength and osteogenicity.

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

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7
Figure 8
Figure 9

Similar content being viewed by others

References

  1. Akasaka, T., A. Yokoyama, M. Matsuoka, T. Hashimoto, and F. Watari. Thin films of single-walled carbon nanotubes promote human osteoblastic cells (Saos-2) proliferation in low serum concentrations. Mater. Sci. Eng. C 30:391–399, 2010.

    Article  CAS  Google Scholar 

  2. Bacakova, L., L. Grausova, J. Vacik, A. Fraczek, S. Blazewicz, A. Kromka, M. Vanecek, and V. Svorcik. Improved adhesion and growth of human osteoblast-like MG 63 cells on biomaterials modified with carbon nanoparticles. Diam. Relat. Mater. 16:2133–2140, 2007.

    Article  CAS  Google Scholar 

  3. Balasundaram, G., M. Sato, and T. J. Webster. Using hydroxyapatite nanoparticles and decreased crystallinity to promote osteoblast adhesion similar to functionalizing with RGD. Biomaterials 27:2798–2805, 2006.

    Article  PubMed  CAS  Google Scholar 

  4. Baughman, R. H., A. A. Zakhidov, and W. A. de Heer. Carbon nanotubes—the route toward applications. Science 297:787–792, 2002.

    Article  PubMed  CAS  Google Scholar 

  5. Boyan, B. D., T. W. Hummert, D. D. Dean, and Z. Schwartz. Role of material surfaces in regulating bone and cartilage cell response. Biomaterials 17:137–146, 1996.

    Article  PubMed  CAS  Google Scholar 

  6. Curtis, A., and C. Wilkinson. New depths in cell behaviour: reactions of cells to nanotopography. Biochem. Soc. Symp. 65:15–26, 1999.

    PubMed  CAS  Google Scholar 

  7. D’Angelo, F., I. Armentano, S. Mattioli, L. Crispoltoni, R. Tiribuzi, G. G. Cerulli, C. A. Palmerini, J. M. Kenny, S. Martino, and A. Orlacchio. Micropatterned hydrogenated amorphous carbon guides mesenchymal stem cells towards neuronal differentiation. Eur. Cells Mater. 20:231–244, 2010.

    Google Scholar 

  8. D’Lima, D. D., S. M. Lemperle, P. C. Chen, R. E. Holmes, and C. W. Colwell, Jr. Bone response to implant surface morphology. J. Arthroplasty 13:928–934, 1998.

    Article  PubMed  Google Scholar 

  9. Donaldson, K., R. Aitken, L. Tran, V. Stone, R. Duffin, G. Forrest, and A. Alexander. Carbon nanotubes: a review of their properties in relation to pulmonary toxicology and workplace safety. Toxicol. Sci. 92:5–22, 2006.

    Article  PubMed  CAS  Google Scholar 

  10. Donaldson, K., V. Stone, C. L. Tran, W. Kreyling, and P. J. A. Borm. Nanotoxicology. Occup. Environ. Med. 61:727–728, 2004.

    Article  PubMed  CAS  Google Scholar 

  11. Elias, K. L., R. L. Price, and T. J. Webster. Enhanced functions of osteoblasts on nanometer diameter carbon fibers. Biomaterials 23:3279–3287, 2002.

    Article  PubMed  CAS  Google Scholar 

  12. Feighan, J. E., V. M. Goldberg, D. Davy, J. A. Parr, and S. Stevenson. The influence of surface-blasting on the incorporation of titanium-alloy implants in a rabbit intramedullary model. J. Bone Jt. Surg. 77:1380–1395, 1995.

    CAS  Google Scholar 

  13. Gloria, A., R. De Santis, and L. Ambrosio. Polymer-based composite scaffolds for tissue engineering. J. Appl. Biomater. Biomech. 8:57–67, 2010.

    PubMed  CAS  Google Scholar 

  14. Goldberg, V. M., S. Stevenson, J. Feighan, and D. Davy. Biology of grit-blasted titanium-alloy implants. Clin. Orthop. Relat. Res. 319:122–129, 1995.

    PubMed  Google Scholar 

  15. Habraken, W. J., J. G. Wolke, A. G. Mikos, and J. A. Jansen. Injectable PLGA microsphere/calcium phosphate cements: physical properties and degradation characteristics. J. Biomater. Sci. Polym. Ed. 17:1057–1074, 2006.

    Article  PubMed  CAS  Google Scholar 

  16. Iijima, S. Helical microtubules of graphitic carbon. Nature 354:56–58, 1991.

    Article  CAS  Google Scholar 

  17. Jadlowiec, J. A., A. B. Celil, and J. O. Hollinger. Bone tissue engineering: recent advances and promising therapeutic agents. Expert Opin. Biol. Ther. 3:409–423, 2003.

    PubMed  CAS  Google Scholar 

  18. Jensen, A. W., S. R. Wilson, and D. I. Schuster. Biological applications of fullerenes. Bioorg. Med. Chem. 4:767–779, 1996.

    Article  PubMed  CAS  Google Scholar 

  19. Karageorgiou, V., and D. Kaplan. Porosity of 3D biomaterial scaffolds and osteogenesis. Biomaterials 26:5474–5491, 2005.

    Article  PubMed  CAS  Google Scholar 

  20. Kessler, P., M. Thorwarth, A. Bloch-Birkholz, E. Nkenke, and F. W. Neukam. Harvesting of bone from the iliac crest–comparison of the anterior and posterior sites. Br. J. Oral Maxillofac. Surg. 43:51–56, 2005.

    Article  PubMed  CAS  Google Scholar 

  21. Khan, Y. M., D. S. Katti, and C. T. Laurencin. Novel polymer-synthesized ceramic composite-based system for bone repair: an in vitro evaluation. J. Biomed. Mater. Res. A 69:728–737, 2004.

    Article  PubMed  Google Scholar 

  22. Khang, D., J. Choi, Y. M. Im, Y. J. Kim, J. H. Jang, S. S. Kang, T. H. Nam, J. Song, and J. W. Park. Role of subnano-, nano- and submicron-surface features on osteoblast differentiation of bone marrow mesenchymal stem cells. Biomaterials 33:5997–6007, 2012.

    Article  PubMed  CAS  Google Scholar 

  23. Kim, S. S., M. Sun Park, O. Jeon, C. Yong Choi, and B. S. Kim. Poly(lactide-co-glycolide)/hydroxyapatite composite scaffolds for bone tissue engineering. Biomaterials 27:1399–1409, 2006.

    Article  PubMed  CAS  Google Scholar 

  24. Kretlow, J. D., and A. G. Mikos. Review: mineralization of synthetic polymer scaffolds for bone tissue engineering. Tissue Eng. 13:927–938, 2007.

    Article  PubMed  CAS  Google Scholar 

  25. Langer, R., and D. A. Tirrell. Designing materials for biology and medicine. Nature 428:487–492, 2004.

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  Google Scholar 

  27. Laurencin, C. T., A. M. A. Ambrosio, M. D. Borden, and J. A. Cooper. Tissue engineering: orthopedic applications. Annu. Rev. Biomed. Eng. 1:19–46, 1999.

    Article  PubMed  CAS  Google Scholar 

  28. Liu, X., and P. X. Ma. Polymeric scaffolds for bone tissue engineering. Ann. Biomed. Eng. 32:477–486, 2004.

    Article  PubMed  Google Scholar 

  29. Martinelli, V., G. Cellot, F. M. Toma, C. S. Long, J. H. Caldwell, L. Zentilin, M. Giacca, A. Turco, M. Prato, L. Ballerini, and L. Mestroni. Carbon nanotubes promote growth and spontaneous electrical activity in cultured cardiac myocytes. Nano Lett. 12:1831–1838, 2012.

    Article  PubMed  CAS  Google Scholar 

  30. Meng, S. Y., Z. Zhang, and M. Rouabhia. Accelerated osteoblast mineralization on a conductive substrate by multiple electrical stimulation. J. Bone Miner. Metab. 29:535–544, 2011.

    Article  PubMed  CAS  Google Scholar 

  31. Mikael, P. E., and S. P. Nukavarapu. Functionalized carbon nanotube composite scaffolds for bone tissue engineering: prospects and progress. J. Biomater. Tissue Eng. 1:76–85, 2011.

    Google Scholar 

  32. Murphy, W. L., and D. J. Mooney. Molecular-scale biomimicry. Nat. Biotechnol. 20:30–31, 2002.

    Article  PubMed  CAS  Google Scholar 

  33. Nakajima, T., H. Iizuka, S. Tsutsumi, M. Kayakabe, and K. Takagishi. Evaluation of posterolateral spinal fusion using mesenchymal stem cells: differences with or without osteogenic differentiation. Spine (Phila Pa 1976) 32:2432–2436, 2007.

    Article  Google Scholar 

  34. Narimissa, E., R. Gupta, M. Bhaskaran, and S. Sriram. Influence of nano-graphite platelet concentration on onset of crystalline degradation in polylactide composites. Polym. Degrad. Stab. 97:829–832, 2012.

    Article  CAS  Google Scholar 

  35. Rezwan, K., Q. Z. Chen, J. J. Blaker, and A. R. Boccaccini. Biodegradable and bioactive porous polymer/inorganic composite scaffolds for bone tissue engineering. Biomaterials 27:3413–3431, 2006.

    Article  PubMed  CAS  Google Scholar 

  36. Rho, J. Y., L. Kuhn-Spearing, and P. Zioupos. Mechanical properties and the hierarchical structure of bone. Med. Eng. Phys. 20:92–102, 1998.

    Article  PubMed  CAS  Google Scholar 

  37. Saito, E., H. Kang, J. M. Taboas, A. Diggs, C. L. Flanagan, and S. J. Hollister. Experimental and computational characterization of designed and fabricated 50:50 PLGA porous scaffolds for human trabecular bone applications. J. Mater. Sci. Mater. Med. 21:2371–2383, 2010.

    Article  PubMed  CAS  Google Scholar 

  38. Saito, N., Y. Usui, K. Aoki, N. Narita, M. Shimizu, K. Hara, N. Ogiwara, K. Nakamura, N. Ishigaki, H. Kato, et al. Carbon nanotubes: biomaterial applications. Chem. Soc. Rev. 38:1897–1903, 2009.

    Article  PubMed  CAS  Google Scholar 

  39. Saito, N., Y. Usui, K. Aoki, N. Narita, M. Shimizu, N. Ogiwara, K. Nakamura, N. Ishigaki, H. Kato, S. Taruta, and M. Endo. Carbon nanotubes for biomaterials in contact with bone. Curr. Med. Chem. 15:523–527, 2008.

    Article  PubMed  CAS  Google Scholar 

  40. Saotome, T., K. Kokubo, S. Shirakawa, T. Oshima, and H. T. Hahn. Polymer nanocomposites reinforced with C-60 fullerene: effect of hydroxylation. J. Compos. Mater. 45:2595–2601, 2011.

    Article  CAS  Google Scholar 

  41. Schliephake, H., H. A. Weich, C. Dullin, R. Gruber, and S. Frahse. Mandibular bone repair by implantation of rhBMP-2 in a slow release carrier of polylactic acid—an experimental study in rats. Biomaterials 29:103–110, 2008.

    Article  PubMed  CAS  Google Scholar 

  42. Shi, X. F., B. Sitharaman, Q. P. Pham, F. Liang, K. Wu, W. E. Billups, L. J. Wilson, and A. G. Mikos. Fabrication of porous ultra-short single-walled carbon nanotube nanocomposite scaffolds for bone tissue engineering. Biomaterials 28:4078–4090, 2007.

    Article  PubMed  CAS  Google Scholar 

  43. Silber, J. S., D. G. Anderson, S. D. Daffner, B. T. Brislin, J. M. Leland, A. S. Hilibrand, A. R. Vaccaro, and T. J. Albert. Donor site morbidity after anterior iliac crest bone harvest for single-level anterior cervical discectomy and fusion. Spine (Phila Pa 1976) 28:134–139, 2003.

    Article  Google Scholar 

  44. Singh, R., D. Pantarotto, L. Lacerda, G. Pastorin, C. Klumpp, M. Prato, A. Bianco, and K. Kostarelos. Tissue biodistribution and blood clearance rates of intravenously administered carbon nanotube radiotracers. Proc. Natl Acad. Sci. USA 103:3357–3362, 2006.

    Article  PubMed  CAS  Google Scholar 

  45. Spalazzi, J. P., E. Dagher, S. B. Doty, X. E. Guo, S. A. Rodeo, and H. H. Lu. In vivo evaluation of a multiphased scaffold designed for orthopaedic interface tissue engineering and soft tissue-to-bone integration. J. Biomed. Mater. Res. A 86:1–12, 2008.

    PubMed  Google Scholar 

  46. Supronowicz, P. R., P. M. Ajayan, K. R. Ullmann, B. P. Arulanandam, D. W. Metzger, and R. Bizios. Novel current-conducting composite substrates for exposing osteoblasts to alternating current stimulation. J. Biomed. Mater. Res. 59:499–506, 2002.

    Article  PubMed  CAS  Google Scholar 

  47. Tseng, I. H., H. C. Lin, M. H. Tsai, and D. S. Chen. Thermal conductivity and morphology of silver-filled multiwalled carbon nanotubes/polyimide nanocomposite films. J. Appl. Polym. Sci. 126:E182–E187, 2012.

    Article  CAS  Google Scholar 

  48. Webster, T. J., and J. U. Ejiofor. Increased osteoblast adhesion on nanophase metals: Ti, Ti6Al4V, and CoCrMo. Biomaterials 25:4731–4739, 2004.

    Article  PubMed  CAS  Google Scholar 

  49. Wick, P., P. Manser, L. K. Limbach, U. Dettlaff-Weglikowska, F. Krumeich, S. Roth, W. J. Stark, and A. Bruinink. The degree and kind of agglomeration affect carbon nanotube cytotoxicity. Toxicol. Lett. 168:121–131, 2007.

    Article  PubMed  CAS  Google Scholar 

  50. Yi, C. Q., D. D. Liu, C. C. Fong, J. C. Zhang, and M. S. Yang. Gold nanoparticles promote osteogenic differentiation of mesenchymal stem cells through p38 MAPK pathway. ACS Nano 4:6439–6448, 2010.

    Article  PubMed  CAS  Google Scholar 

  51. Zanello, L. P., B. Zhao, H. Hu, and R. C. Haddon. Bone cell proliferation on carbon nanotubes. Nano Lett. 6:562–567, 2006.

    Article  PubMed  CAS  Google Scholar 

  52. Zimmermann, C. E., B. I. Borner, A. Hasse, and P. Sieg. Donor site morbidity after microvascular fibula transfer. Clin. Oral Investig. 5:214–219, 2001.

    Article  PubMed  CAS  Google Scholar 

  53. Zinger, O., K. Anselme, A. Denzer, P. Habersetzer, M. Wieland, J. Jeanfils, P. Hardouin, and D. Landolt. Time-dependent morphology and adhesion of osteoblastic cells on titanium model surfaces featuring scale-resolved topography. Biomaterials 25:2695–2711, 2004.

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

The authors thank Dr. Tarek Shazly and Dr. Qian Wang at the University of South Carolina, for their help in scaffold mechanical strength and surface roughness measurements.

Author information

Authors and Affiliations

  1. Biomedical Engineering Program, University of South Carolina, Columbia, SC, 29208, USA

    Qingsu Cheng & Ehsan Jabbarzadeh

  2. Department of Chemical Engineering, University of South Carolina, Columbia, SC, 29208, USA

    Katy Rutledge & Ehsan Jabbarzadeh

  3. Department of Orthopaedic Surgery, University of South Carolina School of Medicine, Columbia, SC, 29209, USA

    Ehsan Jabbarzadeh

Authors
  1. Qingsu Cheng
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Katy Rutledge
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ehsan Jabbarzadeh
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ehsan Jabbarzadeh.

Additional information

Associate Editor K. A. Athanasiou oversaw the review of this article.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Cheng, Q., Rutledge, K. & Jabbarzadeh, E. Carbon Nanotube–Poly(lactide-co-glycolide) Composite Scaffolds for Bone Tissue Engineering Applications. Ann Biomed Eng 41, 904–916 (2013). https://doi.org/10.1007/s10439-012-0728-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10439-012-0728-8

Keywords

Search

Navigation