Efficacy of silicate-substituted calcium phosphate with enhanced strut porosity as a standalone bone graft substitute and autograft extender in an ovine distal femoral critical defect model

  • Stacy A. HutchensEmail author
  • Charlie Campion
  • Michel Assad
  • Madeleine Chagnon
  • Karin A. Hing
Clinical Applications of Biomaterials Original Research
Part of the following topical collections:
  1. Clinical Applications of Biomaterials


A synthetic bone graft substitute consisting of silicate-substituted calcium phosphate with increased strut porosity (SiCaP EP) was evaluated in an ovine distal femoral critical sized metaphyseal defect as a standalone bone graft, as an autologous iliac crest bone graft (ICBG) extender (SiCaP EP/ICBG), and when mixed with bone marrow aspirate (SiCaP EP/BMA). Defects were evaluated after 4, 8, and 12 weeks with radiography, decalcified paraffin-embedded histopathology, non-decalcified resin-embedded histomorphometry, and mechanical indentation testing. All test groups exhibited excellent biocompatibility and osseous healing as evidenced by an initial mild inflammatory response followed by neovascularization, bone growth, and marrow infiltration throughout all SiCaP EP-treated defects. SiCaP EP/ICBG produced more bone at early time points, while all groups produced similar amounts of bone at later time points. SiCaP EP/ICBG likewise showed more favorable mechanical properties at early time points, but was equivalent to SiCaP EP and SiCaP EP/BMA at later time points. This study demonstrates that SiCaP EP is efficacious as a standalone bone graft substitute, mixed with BMA, and as an autograft extender.


Bone Graft Bone Marrow Aspirate Bone Graft Substitute Iliac Crest Bone Graft Ultimate Compressive Strength 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



This research study was funded by Baxter Healthcare.


  1. 1.
    Boanini E, Gazzano M, Bigi A. Ionic substitutions in calcium phosphates synthesized at low temperature. Acta Biomater. 2010;6(6):1882–94.CrossRefGoogle Scholar
  2. 2.
    Carlisle EM. Silicon: a possible factor in bone calcification. Science. 1970;167(916):279–80.CrossRefGoogle Scholar
  3. 3.
    Carlisle EM. Silicon: a requirement in bone formation independent of vitamin D1. Calcif Tissue Int. 1981;33(1):27–34.CrossRefGoogle Scholar
  4. 4.
    Guth K, Campion C, Buckland T, Hing KA. Surface physiochemistry affects protein adsorption to stoichiometric and silicate-substituted microporous hydroxyapatites. Adv Eng Mater. 2010;12(4):B113–21.CrossRefGoogle Scholar
  5. 5.
    Guth K, Campion C, Buckland T, Hing KA. Effect of silicate-substitution on attachment and early development of human osteoblast-like cells seeded on microporous hydroxyapatite discs. Adv Eng Mater. 2010;12(1–2):B26–36.CrossRefGoogle Scholar
  6. 6.
    Cameron K, Travers P, Chander C, Buckland T, Campion C, Noble B. Directed osteogenic differentiation of human mesenchymal stem/precursor cells on silicate substituted calcium phosphate. J Biomed Mater Res A. 2013;101(1):13–22.CrossRefGoogle Scholar
  7. 7.
    Hing KA, Revell PA, Smith N, Buckland T. Effect of silicon level on rate, quality and progression of bone healing within silicate-substituted porous hydroxyapatite scaffolds. Biomaterials. 2006;27(29):5014–26.CrossRefGoogle Scholar
  8. 8.
    Hing KA, Wilson LF, Buckland T. Comparative performance of three ceramic bone graft substitutes. Spine J. 2007;7(4):475–90.CrossRefGoogle Scholar
  9. 9.
    Jenis LG, Banco RJ. Efficacy of silicate-substituted calcium phosphate ceramic in posterolateral instrumented lumbar fusion. Spine (Phila Pa 1976). 2010;35(20):E1058–63.CrossRefGoogle Scholar
  10. 10.
    Pomeroy GC, DeBen S. Ankle arthrodesis with silicate-substituted calcium phosphate bone graft. Foot Ankle Online J. 2013;6(1):2.CrossRefGoogle Scholar
  11. 11.
    Campion CR, Ball SL, Clarke DL, Hing KA. Microstructure and chemistry affects apatite nucleation on calcium phosphate bone graft substitutes. J Mater Sci Mater Med. 2013;24(3):597–610.CrossRefGoogle Scholar
  12. 12.
    De Godoy RF, Hutchens S, Campion C, Blunn G. Silicate-substituted calcium phosphate with enhanced strut porosity stimulates osteogenic differentiation of human mesenchymal stem cells. J Mater Sci Mater Med. 2015;26(1):5387. doi: 10.1007/s10856-015-5387-5.CrossRefGoogle Scholar
  13. 13.
    Campion C, Chander C, Buckland T, Hing K. Increasing strut porosity in silicate-substituted calcium-phosphate bone graft substitutes enhances osteogenesis. J Biomed Mater Res B Appl Biomater. 2011;97(2):245–54.CrossRefGoogle Scholar
  14. 14.
    Fredericks DC, Petersen EB, Saihi N, Corley KGN, DeVries N, Grosland NM, Smucker JD. Evaluation of a novel silicate substituted hydroxyapatite bone graft substitute in a rabbit posterolateral fusion model. Iowa Orthop J. 2013;33:25–32.Google Scholar
  15. 15.
    Fredericks DC, Petersen EB, Al-Hilli A, Nepola JV, Gandhi AA, Kode S, Grosland NM, Smucker JD. In: Assessment of silicate-substituted calcium phosphate bone graft in a rabbit posterolateral fusion model with concurrent chemotherapy. Transactions of the 58th Annual Meeting of the Orthopaedic Research Society, 2012; p. 1112.Google Scholar
  16. 16.
    Coathup M, Samizadeh S, Amogbokpa J, Fang SY, Hing KA, Buckland T, Blunn GW. The osteoinductivity of silicon substituted hydroxyapatite. J Bone Joint Surg Am. 2011;93A(23):2219–26.Google Scholar
  17. 17.
    Coathup MJ, Hing KA, Samizadeh S, Chan O, Fang YS, Campion C, Buckland T, Blunn GW. Effect of increased strut porosity of calcium phosphate bone graft substitute biomaterials on osteoinduction. J Biomed Mater Res A. 2012;100(6):1550–5.CrossRefGoogle Scholar
  18. 18.
    Chan O, Coathup MJ, Nesbitt A, Ho CY, Hing KA, Buckland T, Campion C, Blunn GW. The effects of microporosity on osteoinduction of calcium phosphate bone graft substitute biomaterials. Acta Biomater. 2012;8(7):2788–94.CrossRefGoogle Scholar
  19. 19.
    Hing KA, Annaz B, Saeed S, Revell PA, Buckland T. Microporosity enhances bioactivity of synthetic bone graft substitutes. J Mat Sci Mar Med. 2005;16:467–75.CrossRefGoogle Scholar
  20. 20.
    Chiang YM, Birnie DP III, Kingery WD. Physical ceramics: principles for ceramic science and engineering. New York: Wiley; 1997.Google Scholar
  21. 21.
    Hing KA. Bioceramic bone graft substitutes: influence of porosity and chemistry. Int J Appl Ceram Technol. 2005;2:184–99.CrossRefGoogle Scholar
  22. 22.
    Nuss KM, Auer JA, Boos A, von Rechenberg B. An animal model in sheep for biocompatibility testing of biomaterials in cancellous bones. BMC Musculoskelet Disord. 2006;7:67.CrossRefGoogle Scholar
  23. 23.
    Toth JM, Boden SD, Burkus JK, Badura JM, Peckham SM, McKay WF. Short-term osteoclastic activity induced by locally high concentrations of recombinant human bone morphogenetic protein-2 in a cancellous bone environment. Spine (Phila Pa 1976). 2009;34(6):539–50.CrossRefGoogle Scholar
  24. 24.
    van der Pol U, Mathieu L, Zeiter S, Bourban PE, Zambelli PY, Pearce SG, Bouré LP, Pioletti DP. Augmentation of bone defect healing using a new biocomposite scaffold: an in vivo study in sheep. Acta Biomater. 2010;6(9):3755–62.CrossRefGoogle Scholar
  25. 25.
    Walsh WR, Morberg P, Yu Y, Yang JL, Haggard W, Sheath PC, Svehla M, Bruce WJ. Response of a calcium sulfate bone graft substitute in a confined cancellous defect. Clin Orthop Relat Res. 2003;406:228–36.CrossRefGoogle Scholar
  26. 26.
    Leniz P, Ripalda P, Forriol F. The incorporation of different sorts of cancellous bone graft and the reaction of the host bone. A histomorphometric study in sheep. Int Orthop. 2004;28(1):2–6.CrossRefGoogle Scholar
  27. 27.
    Gisep A, Wieling R, Bohner M, Matter S, Schneider E, Rahn B. Resorption patterns of calcium-phosphate cements in bone. J Biomed Mater Res A. 2003;66(3):532–40.CrossRefGoogle Scholar
  28. 28.
    Pearce AI, Richards RG, Milz S, Schneider E, Pearce SG. Animal models for implant biomaterial research in bone: a review. Eur Cell Mater. 2007;13:1–10.Google Scholar
  29. 29.
    Martini L, Fini M, Giavaresi G, Giardino R. Sheep model in orthopedic research: a literature review. Comp Med. 2001;51(4):292–9.Google Scholar
  30. 30.
    Baramki HG, Steffen T, Lander P, Chang M, Marchesi D. The efficacy of interconnected porous hydroxyapatite in achieving posterolateral lumbar fusion in sheep. Spine (Phila Pa 1976). 2000;25(9):1053–60.CrossRefGoogle Scholar
  31. 31.
    Steffen T, Marchesi D, Aebi M. Posterolateral and anterior interbody spinal fusion models in the sheep. Clin Orthop Relat Res. 2000;371:28–37.CrossRefGoogle Scholar
  32. 32.
    Moore DC, Chapman MW, Manske D. The evaluation of a biphasic calcium phosphate ceramic for use in grafting long-bone diaphyseal defects. J Orthop Res. 1987;5(3):356–65.CrossRefGoogle Scholar
  33. 33.
    Weitao Y, Kangmei K, Xinjia W, Weili Q. Bone regeneration using an injectable calcium phosphate/autologous iliac crest bone composites for segmental ulnar defects in rabbits. J Mater Sci Mater Med. 2008;19(6):2485–92.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  1. 1.Baxter Healthcare CorporationDeerfieldUSA
  2. 2.Orthopedics and Biomaterials LaboratoryAccelLAB Inc.BoisbriandCanada
  3. 3.Institute of BioengineeringSchool of Engineering and Materials Science at Queen Mary University of LondonLondonUK

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