Skip to main content

Advertisement

SpringerLink
Log in

Unitary Bioresorbable Cage/Core Bone Graft Substitutes for Spinal Arthrodesis Coextruded from Polycaprolactone Biocomposites

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

Abstract

A unitary bioresorbable cage/core bone graft substitute consisting of a stiff cage and a softer core with interconnected porosity is offered for spinal arthrodesis. Polycaprolactone, PCL, was used as the matrix and hydroxyapatite, HA, and β-tricalcium phosphate, TCP, were used in the formulation of the cage layer to impart modulus increase and osteoconductivity while the core consisted solely of PCL. The crystallinity, biodegradation rate (under accelerated conditions) and mechanical properties, i.e., the uniaxial compression, relaxation modulus upon step compression and cyclic compressive fatigue properties, of the co-extruded cage/core bone graft substitutes could be manipulated by changes in the concentration of HA/TCP in the cage layer. The cyclic fatigue behavior of the cage/core bone graft substitutes were also compared to the behavior of bovine vertebral cancellous bone characterized under similar testing conditions. The biocompatibility of the cage/core bone graft substitutes were assessed via in vitro culturing of human bone marrow derived stromal cells, BMSCs. The cell proliferation rates, time dependencies of the alkaline phosphates (ALP) activity and the expressions of bone markers, i.e., Runx2, ALP, collagen type I, osteopontin and osteocalcin, and the collected μ-CT images demonstrated the differentiation of BMSCs via osteogenic lineage and formation of mineralized bone tissue to indicate the biocompatibility of the cage/core bone graft substitutes.

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. Abbah, S. A., C. X. L. Lam, D. W. Hutmacher, J. C. H. Goh, and H. Wong. Biological performance of a polycaprolactone-based scaffold used as fusion cage device in a large animal model of spinal reconstructive surgery. Biomaterials 30:5086–5093, 2009.

    Article  PubMed  CAS  Google Scholar 

  2. Agrillo, U., L. Mastronardi, and F. Puzzilli. Anterior cervical fusion with carbon fiber cage containing coralline hydroxyapatite: preliminary observations in 45 consecutive cases of soft-disc herniation. J. Neurosurg. 96:273–276, 2002.

    Article  PubMed  CAS  Google Scholar 

  3. Alini, M., S. M. Eisenstein, K. Ito, C. Little, A. A. Kettler, K. Masuda, J. Melrose, J. Ralphs, I. Stokes, and H. J. Wilke. Are animal models useful for studying human disc disorders/degeneration? Eur. Spine. J. 17(1):2–19, 2008.

    Article  PubMed  Google Scholar 

  4. Arinzeh, T. L., T. Tran, J. Mcalary, and G. Daculsi. A comparative study of biphasic calcium phosphate ceramics for human mesenchymal stem-cell-induced bone formation. Biomaterials 26:3631–3638, 2005.

    Article  PubMed  CAS  Google Scholar 

  5. Burr, D. B., C. Milgrom, D. Fyhrie, M. Forwood, M. Nyska, A. Finestone, S. Hoshaw, E. Saiag, and A. Simkin. In vivo measurement of human tibial strains during vigorous activity. Bone 18(5):405–410, 1996.

    Article  PubMed  CAS  Google Scholar 

  6. Byers, B. A., and A. J. Garcia. Exogenous runx2 expression enhances in vitro osteoblastic differentiation and mineralization in primary bone marrow stromal cells. Tissue Eng. A 10(11/12):1623–1632, 2004.

    CAS  Google Scholar 

  7. Carson, J. S., and M. P. G. Bostrom. Synthetic bone scaffolds and fracture repair. Injury 38S1:33–37, 2007.

    Article  Google Scholar 

  8. Chang, W. C., H. K. Tsou, W. S. Chen, C. C. Chen, and C. C. Shen. Preliminary comparison of radiolucent cages containing either autogenous cancellous bone or hydroxyapatite graft in multilevel cervical fusion. J. Clin. Neurosci. 16:793–796, 2009.

    Article  PubMed  Google Scholar 

  9. Charlebois, M., M. Pretterklieber, and P. K. Zysset. The role of fabric in the large strain compressive behavior of human trabecular bone. J. Biomech. Eng. 132(12):121006, 2010.

    Article  PubMed  Google Scholar 

  10. Chau, A. M. T., and R. J. Mobbs. Bone graft substitutes in anterior cervical discectomy and fusion. Eur. Spine J. 18:449–464, 2009.

    Article  PubMed  Google Scholar 

  11. Ciapetti, G., L. Ambrosio, G. Marletta, N. Baldini, and A. Giunti. Human bone marrow stromal cells: in vitro expansion and differentiation for bone engineering. Biomaterials 27(36):6150–6160, 2006.

    Article  PubMed  CAS  Google Scholar 

  12. Daculsi, G., O. Laboux, O. Malard, and P. Weiss. Current state of the art of biphasic calcium phosphate bioceramics. J. Mater. Sci.: Mater. Med. 14:195–200, 2003.

    Article  CAS  Google Scholar 

  13. Debusscher, F., S. Aunoble, Y. Alsawad, D. Clement, and J. C. Le Huec. Anterior cervical fusion with a bio-resorbable composite cage (beta TCP-PLLA): clinical and radiological results from a prospective study on 20 patients. Eur. Spine J. 18:1314–1320, 2009.

    Article  PubMed  CAS  Google Scholar 

  14. Dendorfer, S., H. J. Maier, D. Taylor, and J. Hammer. Anisotrophy of the fatigue behavior of cancellous bone. J. Biomech. 41:636–641, 2008.

    Article  PubMed  CAS  Google Scholar 

  15. Endres, M., D. W. Hutmacher, A. J. Salgado, C. Kaps, J. Ringe, R. L. Reis, M. Sittinger, A. Brandwood, and J. T. Schantz. Osteogenic induction of human bone marrow-derived mesenchymal progenitor cells in novel synthetic polymer-hydrogel matrices. Tissue Eng. 9(4):689–702, 2003.

    Article  PubMed  CAS  Google Scholar 

  16. Erisken, C., D. M. Kalyon, and H. Wang. Functionally and continuously graded electrospun polycaprolactone and β-tricalcium phosphate nanocomposites for interface tissue engineering applications. Biomaterials 29:4065–4073, 2008.

    Article  PubMed  CAS  Google Scholar 

  17. Faour, O., R. Dimitriou, C. A. Cousins, and P. V. Giannoudis. The use of bone graft substitutes in large cancellous voids: any specific needs? Injury 42:S87–S90, 2011.

    Article  PubMed  Google Scholar 

  18. Giannoudis, P. V., H. Dinopoulos, and E. Tsiridis. Bone substitutes: an update. Injury 36S:S20–S27, 2005.

    Article  Google Scholar 

  19. Goldstein, A. S., T. M. Juarez, C. D. Helmke, M. C. Gustin, and A. G. Mikos. Effect of convection on osteoblastic cell growth and function in biodegradable polymer foam scaffolds. Biomaterials 22:1279–1288, 2001.

    Article  PubMed  CAS  Google Scholar 

  20. Greenwald, A. S., S. D. Boden, V. M. Goldberg, Y. Khan, C. T. Laurecin, and R. N. Rosier. Bone-graft substitutes: facts, fictions, and applications. J. Bone Joint. Surg. Am. 83:S98–S103, 2001.

    Google Scholar 

  21. Guarino, V., P. Taddei, M. Di Foggia, C. Fagnano, G. Ciapetti, and L. Ambrosio. The influence of hydroxyapatite particles on in vitro degradation behavior of poly ε-caprolactone-based composite scaffolds. Tissue Eng. A 15(11):3655–3668, 2009.

    Article  CAS  Google Scholar 

  22. Haddock, S. M., O. C. Yeh, P. V. Mummaneni, W. S. Rosenberg, and T. M. Keaveny. Similarity in the fatigue behavior of trabecular bone across site and species. J. Biomech. 37:181–187, 2004.

    Article  PubMed  Google Scholar 

  23. Harris, C. T., and L. F. Cooper. Comparison of bone graft matrices for human mesenchymal stem cell-directed osteogenesis. J. Biomed. Mater. Res. A 68(4):747–755, 2004.

    Article  PubMed  CAS  Google Scholar 

  24. Harrison, K. L., and M. J. Jenkins. The effect of crystallinity and water absorption on the dynamic mechanical relaxation behaviour of polycaprolactone. Polym Int. 53:1298–1304, 2004.

    Article  CAS  Google Scholar 

  25. Hutmacher, D. W. Scaffolds in tissue engineering bone and cartilage. Biomaterials 21:2529–2543, 2000.

    Article  PubMed  CAS  Google Scholar 

  26. Kalyon, D. M., and M. Malik. An integrated approach for numerical analysis of coupled flow and heat transfer in co-rotating twin screw extruders. Int. Polym. Processing 22:293–302, 2007.

    CAS  Google Scholar 

  27. Kalyon, D. M., D. Yu, and J. Yu. Melt rheology of two engineering plastics: poly(ether imide) and poly (2, 6-dimethyl-1, 4 phenylene ether). J. Rheo. 32(8):789–811, 1988.

    Article  CAS  Google Scholar 

  28. Khan, S. N., E. Tomin, and J. M. Lane. Clinical applications of bone graft substitutes. Orthop. Clin. North. Am. 31(3):389–398, 2000.

    Article  PubMed  CAS  Google Scholar 

  29. Kim, H. J., U. J. Kim, G. Vunjak-Novakovic, B. H. Min, and D. L. Kaplan. Influence of macroporous protein scaffold on bone tissue engineering from bone marrow cells. Biomaterials 26:4442–4452, 2005.

    Article  PubMed  CAS  Google Scholar 

  30. Kohlhauser, C., C. Hellmich, C. Vitale-Brovarone, A. R. Boccaccini, A. Rota, and J. Eberhardsteiner. Ultrasonic characterisation of porous biomaterials across different frequencies. Strain 45:34–44, 2009.

    Article  Google Scholar 

  31. Kruyet, M. C., S. M. Van Gaalen, F. C. Oner, A. J. Verbout, J. D. de Bruijn, and W. J. A. Dhert. Bone tissue engineering and spinal fusion: the potential of hybrid constructs by combining osteoprogenitor cells and scaffolds. Biomaterials 25:1436–1473, 2004.

    Google Scholar 

  32. Kurtz, S. M., and J. N. Devine. PEEK biomaterials in trauma, orthopedic, and spinal implants. Biomaterials 28:4845–4869, 2007.

    Article  PubMed  CAS  Google Scholar 

  33. Lam, C. X. F., M. M. Savalani, S. Teoh, and D. W. Hutmacher. Dynamics of in vitro polymer degradation of polycaprolactone-based scaffolds: accelerated versus simulated physiological conditions. Biomed. Mater. 3:034108, 2008.

    Article  PubMed  Google Scholar 

  34. LeGeros, R. Z., S. Lin, R. Rohanizadeh, D. Mijares, and J. P. LeGeros. Biphasic calcium phosphate bioceramics: preparation, properties and applications. J. Mater. Sci.: Mater. Med. 14:201–209, 2003.

    Article  CAS  Google Scholar 

  35. Li, C., C. Vepari, H. J. Jin, H. J. Kim, and D. L. Kaplan. Electrospun silk-BMP-2 scaffolds for bone tissue engineering. Biomaterials 27:31115–33124, 2006.

    Google Scholar 

  36. Li, H., X. Zou, Q. Xue, N. Egund, M. Lind, and C. Bunger. Effects of autogenous bone graft impaction and tricalcium phosphate on anterior interbody fusion in porcine lumbar spine. Acta. Orthop. Scand. 75:456–463, 2003.

    Google Scholar 

  37. Lian, J. B., and G. S. Stein. Concepts of osteoblast growth and differentiation: basis for modulation of cell development and tissue formation. Crit. Rev. Oral. Biol. Med. 3(3):269–305, 1992.

    PubMed  CAS  Google Scholar 

  38. Livingston, T. L., S. Gordon, M. Archambault, S. Kadiyala, K. McIntosh, A. Smith, and S. J. Peter. Mesenchymal stem cells combined with biphasic calcium phosphate ceramics promote bone regeneration. J. Mater. Sci.: Mater. Med. 14:211–218, 2003.

    Article  CAS  Google Scholar 

  39. Malik, M., and D. M. Kalyon. Three-dimensional finite element simulation of processing of generalized Newtonian fluids in counter-rotating and tangential twin screw extruder and die combination. Int. Polym. Process. 20:398–409, 2005.

    CAS  Google Scholar 

  40. Matsuura, M., F. Eckstein, E. M. Lochmuller, and P. K. Zysset. The role of fabric in the quasi-static compressive mechanical properties of human trabecular bone from various anatomical locations. Biomech. Model. Mechanobiol. 7:27–42, 2008.

    Article  PubMed  Google Scholar 

  41. Moore, T. L. A., and L. J. Gibson. Fatigue of bovine trabecular bone. J. Biomech. Eng. 125(6):761–768, 2003.

    Article  PubMed  Google Scholar 

  42. Ng, A. M. H., K. K. Tan, M. Y. Phang, O. Aziyati, G. H. Tan, M. R. Isa, B. S. Aminuddin, M. Naseem, O. Fauziah, and B. H. I. Ruszymah. Differential osteogenic activity of osteoprogenitor cells on HA and TCP/HA scaffold of tissue engineered bone. J. Biomed. Mater. Res. A 85A(2):301–312, 2008.

    Article  CAS  Google Scholar 

  43. O’Halloran, D. M., and A. S. Pandit. Tissue-engineering approach to regenerating the intervertebral disc. Tissue Eng. 13(8):1931–1954, 2007.

    Google Scholar 

  44. Ozkan, S., D. Kalyon, and X. Yu. Functionally graded β-TCP/PCL nanocomposite scaffolds for bone tissue engineering: in vitro evaluation with human fetal osteoblast cells. J. Biomed. Mater. Res. A 92A(3):1007–1018, 2009.

    Google Scholar 

  45. Rai, B., J. L. Lin, Z. X. Lim, R. E. Guldberg, D. W. Hutmacher, and S. M. Cool. Differences between in vitro viability and differentiation and in vivo bone-forming efficacy of human mesenchymal stem cells cultured on PCL-TCP scaffolds. Biomaterials 31(31):7960–7970, 2010.

    Article  PubMed  CAS  Google Scholar 

  46. Rapillard, L., M. Charlebois, and P. K. Zysset. Compressive fatigue behavior of human vertebral trabecular bone. J. Biomech. 39:2133–2139, 2006.

    Article  PubMed  Google Scholar 

  47. Reignier, J., and M. A. Huneault. Preparation, of interconnected poly (ε-caprolactone) porous scaffolds by a combination of polymer and salt particulate leaching. Polymer 47:4703–4717, 2006.

    Article  CAS  Google Scholar 

  48. Schopper, C., F. Ziya-Ghazvini, W. Goriwoda, D. Moser, F. Wanschitz, E. Spassova, G. Lagogiannis, A. Auterith, and R. Ewers. HA/TCP compounding of a porous CaP biomaterial improves bone formation and scaffold degradation—a long-term histological study. J. Biomed. Mater. Res. B Appl. Biomater. 74(1):458–467, 2005.

    PubMed  Google Scholar 

  49. Setzer, B., M. Bachle, M. C. Metzger, and R. J. Kohal. The gene-expression and phenotypic response of hFOB 1.19 osteoblasts to surface-modified titanium and zirconia. Biomaterials 30:979–990, 2009.

    Article  PubMed  CAS  Google Scholar 

  50. Shedid, D., K. T. Ugokwe, and E. C. Benzel. Lumbar total disc replacement compared with spinal fusion: treatment choice and evaluation of outcome. Nat. Clin. Pract. Neurol. 1(1):4–5, 2005.

    Article  PubMed  Google Scholar 

  51. Shikinami, Y., and M. Okuno. Mechanical evaluation of novel spinal interbody fusion cages made of bioactive, resorbable composites. Biomaterials 24:3161–3170, 2003.

    Article  PubMed  CAS  Google Scholar 

  52. Smit, T. H., T. A. P. Engels, S. H. M. Söntjens, and L. E. Govaert. Time-dependent failure in load-bearing polymers: a potential hazard in structural applications in polylactides. J. Mater. Sci.: Mater. Med. 21:871–878, 2010.

    Article  CAS  Google Scholar 

  53. Topolinski, T., A. Cichanski, A. Mazurkiewicz, and K. Nowicki. Study of the behavior of the trabecular bone under cyclic compression with stepwise increasing amplitude. J. Mech. Behav. Biomed. Mater., 2011. doi:10.1016/j.jmbbm.2011.05.032.

  54. Valdevit, A. Dynamic Biochemical Comparison of Single Versus Dual Threaded Pedicle Screws. PhD Thesis, Stevens Institute of Technology, Hoboken, NJ, 2010.

  55. Wang, J., M. K. Cheung, and Y. Mi. Miscibility and morphology in crystalline/amorphous blends of poly(caprolactone)/poly(4-vinylphenol) as studied by DSC, FTIR and 13C solid state NMR. Polymer 43:1357–1364, 2002.

    Article  CAS  Google Scholar 

  56. Wuisman, P. I. J. M., and T. H. Smith. Bioresorbable polymers: heading for a new generation of spinal cages. Eur. Spine J. 15:133–148, 2006.

    Article  PubMed  CAS  Google Scholar 

  57. Yilgor, P., R. A. Sousa, R. L. Reis, N. Hasirci, and V. Hasirci. 3D plotted PCL scaffolds for stem cell based bone tissue engineering. Macromol. Symp. 269:92–99, 2008.

    Article  CAS  Google Scholar 

  58. Yourek, G., S. M. McCormick, J. J. Mao, and G. C. Reilly. Shear stress induces osteogenic differentiation of human mesenchymal stem cells. Regen. Med. 5(5):713–724, 2010.

    Article  PubMed  CAS  Google Scholar 

  59. Zhou, Y., D. W. Hutmacher, S. L. Varawan, and T. M. Lim. In vitro bone engineering based on polycaprolactone and polycaprolactone–tricalcium phosphate composites. Polym. Int. 56:333–342, 2007.

    Article  CAS  Google Scholar 

Download references

Acknowledgments

We are grateful to Material Processing & Research, Inc. of NJ for the consignment of the 7.5 mm twin screw extruder and feeding equipment. We thank Ms. Lyudmila Lukashova from Hospital for Special Surgery of Columbia University for the micro-CT scans of our tissue constructs. The help and suggestions of Ms. Melissa Wiegand and Prof. Xiaojun Yu of Stevens are gratefully acknowledged. This research effort used electron microscopy resources partially funded by the National Science Foundation through NSF Grant DMR-0922522 and we thank Professor Matthew Libera and Dr. Tsengming Chou of Stevens for their generous help in microscopy.

Author information

Authors and Affiliations

  1. Department of Chemical Engineering & Materials Science, Stevens Institute of Technology, Hoboken, NJ, 07030, USA

    Asli Ergun, Daniel Ward & Dilhan M. Kalyon

  2. Department of Chemistry, Chemical Biology & Biomedical Engineering, Stevens Institute of Technology, Hoboken, NJ, 07030, USA

    Rebecca Chung, Antonio Valdevit, Arthur Ritter & Dilhan M. Kalyon

Authors
  1. Asli Ergun
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Rebecca Chung
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Daniel Ward
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Antonio Valdevit
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Arthur Ritter
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Dilhan M. Kalyon
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Dilhan M. Kalyon.

Additional information

Associate Editor Kent Leach oversaw the review of this article.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Figure 1

Typical stress versus strain hysteresis loops of the bovine bone specimens from cyclic compressive fatigue testing. Supplementary material 1 (TIFF 56 kb)

Supplementary material 2 (PDF 28 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ergun, A., Chung, R., Ward, D. et al. Unitary Bioresorbable Cage/Core Bone Graft Substitutes for Spinal Arthrodesis Coextruded from Polycaprolactone Biocomposites. Ann Biomed Eng 40, 1073–1087 (2012). https://doi.org/10.1007/s10439-011-0484-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10439-011-0484-1

Keywords

Search

Navigation