Treatment of periodontal defects in dogs using an injectable composite hydrogel/biphasic calcium phosphate

  • Xavier Struillou
  • Hervé Boutigny
  • Zahi Badran
  • Borhane H. Fellah
  • Olivier Gauthier
  • Sophie Sourice
  • Paul Pilet
  • Thierry Rouillon
  • Pierre Layrolle
  • Pierre WeissEmail author
  • Assem Soueidan


An injectable composite silanized hydroxypropyl methyl cellulose/biphasic calcium phosphate (Si-HPMC/BCP) has been investigated in humans with promising results. The aim of this study was to evaluate his efficacy for treating periodontal defects (canine fenestration and premolar furcation) in dog models. At 3 months, we observed that bone formation around BCP particles in furcation model is more discernible but not statistically significant in defects filled with Si-HPMC/BCP compared to healing in control. We suggest that BCP particles sustain the bone healing process by osteoconduction, while the Si-HPMC hydrogel enhances intergranular cohesion and acts as an exclusion barrier. Furthermore, bone ingrowth is not so distinctive in superficial defects where the biomaterial appears unstable. These results with Si-HPMC/BCP are encouraging. In addition, this biomaterial is easy to use and simplifies the process of filling periodontal lesions. However, more researches are needed to improve the viscosity and hardness to adjust the material to the specificities of periodontal defects.


Inductively Couple Plasma Atomic Emission Spectroscopy Bone Ingrowth Biphasic Calcium Phosphate Enamel Matrix Derivative Guide Tissue Regeneration 
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.


  1. 1.
    Trombelli L, Farina R. Clinical outcomes with bioactive agents alone or in combination with grafting or guided tissue regeneration. J Clin Periodontol. 2008;35(8):117–35. doi: 10.1111/j.1600-051X.2008.01265.x.CrossRefGoogle Scholar
  2. 2.
    Nasr HF, Aichelmann-Reidy ME, Yukna RA. Bone and bone substitutes. Periodontol 2000. 1999;19:74–86.CrossRefGoogle Scholar
  3. 3.
    Pandit N, Gupta R, Gupta S. A comparative evaluation of biphasic calcium phosphate material and bioglass in the treatment of periodontal osseous defects: a clinical and radiological study. J Contemp Dent Pract. 2010;11(2):25–32.Google Scholar
  4. 4.
    LeGeros RZ. Calcium phosphate-based osteoinductive materials. Chem Rev. 2008;108(11):4742–53. doi: 10.1021/cr800427g.CrossRefGoogle Scholar
  5. 5.
    AlGhamdi AS, Shibly O, Ciancio SG. Osseous grafting part II: xenografts and alloplasts for periodontal regeneration—a literature review. J Int Acad Periodontol. 2010;12(2):39–44.Google Scholar
  6. 6.
    AlGhamdi AS, Shibly O, Ciancio SG. Osseous grafting part I: autografts and allografts for periodontal regeneration—a literature review. J Int Acad Periodontol. 2010;12(2):34–8.Google Scholar
  7. 7.
    Daculsi G, Laboux O, Malard O, Weiss P. Current state of the art of biphasic calcium phosphate bioceramics. J Mater Sci Mater Med. 2003;14(3):195–200. doi: 10.1023/A:1022842404495.CrossRefGoogle Scholar
  8. 8.
    Nery EB, LeGeros RZ, Lynch KL, Lee K. Tissue response to biphasic calcium phosphate ceramic with different ratios of HA/beta TCP in periodontal osseous defects. J Periodontol. 1992;63(9):729–35.Google Scholar
  9. 9.
    Hashimoto-Uoshima M, Ishikawa I, Kinoshita A, Weng HT, Oda S. Clinical and histologic observation of replacement of biphasic calcium phosphate by bone tissue in monkeys. Int J Periodontics Restor Dent. 1995;15(2):205–13.Google Scholar
  10. 10.
    Froum SJ, Wallace SS, Cho SC, Elian N, Tarnow DP. Histomorphometric comparison of a biphasic bone ceramic to anorganic bovine bone for sinus augmentation: 6–8 month postsurgical assessment of vital bone formation. A pilot study. Int J Periodontics Restor Dent. 2008;28(3):273–81.Google Scholar
  11. 11.
    Cordaro L, Bosshardt DD, Palattella P, Rao W, Serino G, Chiapasco M. Maxillary sinus grafting with bio-oss or straumann bone ceramic: histomorphometric results from a randomized controlled multicenter clinical trial. Clin Oral Implant Res. 2008;19(8):796–803. doi: 10.1111/j.1600-0501.2008.01565.x.CrossRefGoogle Scholar
  12. 12.
    Friedmann A, Dard M, Kleber BM, Bernimoulin JP, Bosshardt DD. Ridge augmentation and maxillary sinus grafting with a biphasic calcium phosphate: histologic and histomorphometric observations. Clin Oral Implant Res. 2009;20(7):708–14. doi: 10.1111/j.1600-0501.2009.01708.x.CrossRefGoogle Scholar
  13. 13.
    Bodde EW, Wolke JG, Kowalski RS, Jansen JA. Bone regeneration of porous beta-tricalcium phosphate (conduit TCP) and of biphasic calcium phosphate ceramic (biosel) in trabecular defects in sheep. J Biomed Mater Res A. 2007;82(3):711–22. doi: 10.1002/jbm.a.30990.Google Scholar
  14. 14.
    Sculean A, Nikolidakis D, Schwarz F. Regeneration of periodontal tissues: combinations of barrier membranes and grafting materials—biological foundation and preclinical evidence: a systematic review. J Clin Periodontol. 2008;35(8 Suppl):106–16. doi: 10.1111/j.1600-051X.2008.01263.x.CrossRefGoogle Scholar
  15. 15.
    Fatimi A, Tassin JF, Quillard S, Axelos MA, Weiss P. The rheological properties of silated hydroxypropylmethylcellulose tissue engineering matrices. Biomaterials. 2008;29(5):533–43.CrossRefGoogle Scholar
  16. 16.
    Vinatier C, Magne D, Weiss P, Trojani C, Rochet N, Carle GF, et al. A silanized hydroxypropyl methylcellulose hydrogel for the three-dimensional culture of chondrocytes. Biomaterials. 2005;26(33):6643–51. doi: 10.1016/j.biomaterials.2005.04.057.CrossRefGoogle Scholar
  17. 17.
    Vinatier C, Guicheux J, Daculsi G, Layrolle P, Weiss P. Cartilage and bone tissue engineering using hydrogels. Biomed Mater Eng. 2006;16(4 Suppl):S107–13.Google Scholar
  18. 18.
    Fellah BH, Weiss P, Gauthier O, Rouillon T, Pilet P, Daculsi G, et al. Bone repair using a new injectable self-crosslinkable bone substitute. J Orthop Res. 2006;24(4):628–35.CrossRefGoogle Scholar
  19. 19.
    Boix D, Weiss P, Gauthier O, Guicheux J, Bouler JM, Pilet P, et al. Injectable bone substitute to preserve alveolar ridge resorption after tooth extraction: a study in dog. J Mater Sci Mater Med. 2006;17(11):1145–52. doi: 10.1007/s10856-006-0542-7.CrossRefGoogle Scholar
  20. 20.
    Weiss P, Layrolle P, Clergeau LP, Enckel B, Pilet P, Amouriq Y, et al. The safety and efficacy of an injectable bone substitute in dental sockets demonstrated in a human clinical trial. Biomaterials. 2007;28(22):3295–305. doi: 10.1016/j.biomaterials.2007.04.006.CrossRefGoogle Scholar
  21. 21.
    Tatakis DN, Promsudthi A, Wikesjo UM. Devices for periodontal regeneration. Periodontol 2000. 1999;19:59–73.CrossRefGoogle Scholar
  22. 22.
    Wikesjo UM, Selvig KA. Periodontal wound healing and regeneration. Periodontol 2000. 1999;19:21–39.CrossRefGoogle Scholar
  23. 23.
    Daculsi G, Uzel AP, Weiss P, Goyenvalle E, Aguado E. Developments in injectable multiphasic biomaterials. The performance of microporous biphasic calcium phosphate granules and hydrogels. J Mater Sci Mater Med. 2010;21(3):855–61. doi: 10.1007/s10856-009-3914-y.CrossRefGoogle Scholar
  24. 24.
    Bourges X, Weiss P, Coudreuse A, Daculsi G, Legeay G. General properties of silated hydroxyethylcellulose for potential biomedical applications. Biopolymers. 2002;63(4):232–8. doi: 10.1002/bip.10053.CrossRefGoogle Scholar
  25. 25.
    Schmitt M, Weiss P, Bourges X, Amador del Valle G, Daculsi G. Crystallization at the polymer/calcium-phosphate interface in a sterilized injectable bone substitute IBS. Biomaterials. 2002;23(13):2789–94.CrossRefGoogle Scholar
  26. 26.
    Turczyn R, Weiss P, Lapkowski M, Daculsi G. In situ self hardening bioactive composite for bone and dental surgery. J Biomater Sci Polym Ed. 2000;11(2):217–23.CrossRefGoogle Scholar
  27. 27.
    Bourges X, Weiss P, Daculsi G, Legeay G. Synthesis and general properties of silated-hydroxypropyl methylcellulose in prospect of biomedical use. Adv Colloid Interface Sci. 2002;99(3):215–28. doi: 10.1016/S0001-8686(02)00035-0.CrossRefGoogle Scholar
  28. 28.
    Bourges X, Schmitt M, Amouriq Y, Daculsi G, Legeay G, Weiss P. Interaction between hydroxypropyl methylcellulose and biphasic calcium phosphate after steam sterilisation: capillary gas chromatography studies. J Biomater Sci Polym Ed. 2001;12(6):573–9.CrossRefGoogle Scholar
  29. 29.
    Struillou X, Boutigny H, Soueidan A, Layrolle P. Experimental animal models in periodontology: a review. Open Dent J. 2010;4:37–47. doi: 10.2174/1874210601004010037.CrossRefGoogle Scholar
  30. 30.
    Miranda LA, Gomes SC, Soares IJ, Oppermann RV. A resin-modified glass ionomer cement barrier for treating degree II furcation defects: a pilot study in dogs. Acta Odontol Scand. 2006;64(1):37–41. doi: 10.1080/00016350500367520.CrossRefGoogle Scholar
  31. 31.
    Soucacos PN, Johnson EO, Babis G. An update on recent advances in bone regeneration. Injury. 2008;39(Suppl 2):S1–4. doi: 10.1016/S0020-1383(08)70009-3.CrossRefGoogle Scholar
  32. 32.
    Hammarstrom L, Heijl L, Gestrelius S. Periodontal regeneration in a buccal dehiscence model in monkeys after application of enamel matrix proteins. J Clin Periodontol. 1997;24(9 Pt 2):669–77.CrossRefGoogle Scholar
  33. 33.
    Hammarstrom L. Enamel matrix, cementum development and regeneration. J Clin Periodontol. 1997;24(9 Pt 2):658–68.CrossRefGoogle Scholar
  34. 34.
    Sculean A, Donos N, Brecx M, Reich E, Karring T. Treatment of intrabony defects with guided tissue regeneration and enamel-matrix-proteins. An experimental study in monkeys. J Clin Periodontol. 2000;27(7):466–72.CrossRefGoogle Scholar
  35. 35.
    Sculean A, Donos N, Brecx M, Karring T, Reich E. Healing of fenestration-type defects following treatment with guided tissue regeneration or enamel matrix proteins. An experimental study in monkeys. Clin Oral Investig. 2000;4(1):50–6.CrossRefGoogle Scholar
  36. 36.
    Espitalier F, Vinatier C, Lerouxel E, Guicheux J, Pilet P, Moreau F, et al. A comparison between bone reconstruction following the use of mesenchymal stem cells and total bone marrow in association with calcium phosphate scaffold in irradiated bone. Biomaterials. 2009;30(5):763–9.CrossRefGoogle Scholar
  37. 37.
    Kawase T, Okuda K, Kogami H, Nakayama H, Nagata M, Sato T, et al. Human periosteum-derived cells combined with superporous hydroxyapatite blocks used as an osteogenic bone substitute for periodontal regenerative therapy: an animal implantation study using nude mice. J Periodontol. 2010;81(3):420–7. doi: 10.1902/jop.2009.090523.CrossRefGoogle Scholar
  38. 38.
    Sculean A, Windisch P, Szendroi-Kiss D, Horvath A, Rosta P, Becker J, et al. Clinical and histologic evaluation of an enamel matrix derivative combined with a biphasic calcium phosphate for the treatment of human intrabony periodontal defects. J Periodontol. 2008;79(10):1991–9. doi: 10.1902/jop.2008.080009.CrossRefGoogle Scholar
  39. 39.
    Lerouxel E, Weiss P, Giumelli B, Moreau A, Pilet P, Guicheux J, et al. Injectable calcium phosphate scaffold and bone marrow graft for bone reconstruction in irradiated areas: an experimental study in rats. Biomaterials. 2006;27(26):4566–72. doi: 10.1016/j.biomaterials.2006.04.027.CrossRefGoogle Scholar
  40. 40.
    Malard O, Guicheux J, Bouler JM, Gauthier O, de Montreuil CB, Aguado E, et al. Calcium phosphate scaffold and bone marrow for bone reconstruction in irradiated area: a dog study. Bone. 2005;36(2):323–30. doi: 10.1016/j.bone.2004.07.018.CrossRefGoogle Scholar
  41. 41.
    Jegoux F, Goyenvalle E, Cognet R, Malard O, Moreau F, Daculsi G, et al. Mandibular segmental defect regenerated with macroporous biphasic calcium phosphate, collagen membrane, and bone marrow graft in dogs. Arch Otolaryngol Head Neck Surg. 2010;136(10):971–8. doi: 10.1001/archoto.2010.173.CrossRefGoogle Scholar
  42. 42.
    Yuan J, Cui L, Zhang WJ, Liu W, Cao Y. Repair of canine mandibular bone defects with bone marrow stromal cells and porous beta-tricalcium phosphate. Biomaterials. 2007;28(6):1005–13. doi: 10.1016/j.biomaterials.2006.10.015.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Xavier Struillou
    • 1
  • Hervé Boutigny
    • 2
  • Zahi Badran
    • 1
    • 2
  • Borhane H. Fellah
    • 3
  • Olivier Gauthier
    • 3
  • Sophie Sourice
    • 1
  • Paul Pilet
    • 1
  • Thierry Rouillon
    • 1
  • Pierre Layrolle
    • 5
  • Pierre Weiss
    • 1
    Email author
  • Assem Soueidan
    • 1
    • 2
    • 4
  1. 1.INSERM, U791, Laboratory for Osteo-Articular and Dental Tissue Engineering (LIOAD), Faculty of Dental SurgeryUniversity of NantesNantesFrance
  2. 2.Department of Periodontology, Faculty of Dental SurgeryUniversity of NantesNantesFrance
  3. 3.Experimental SurgeryNational Veterinary School of NantesRoute de GachetFrance
  4. 4.ERT 2004University of NantesNantesFrance
  5. 5.INSERM, U957, LPRO, Faculty of MedicineUniversity of NantesNantesFrance

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