Biofunctionality of MBCP ceramic granules (TricOs™) plus fibrin sealant (Tisseel®) versus MBCP ceramic granules as a filler of large periprosthetic bone defects: an investigative ovine study

  • E. GoyenvalleEmail author
  • E. Aguado
  • P. Pilet
  • G. Daculsi


We aimed to quantify bone colonization toward an untreated titanium implant with primary stability following filling of the defect with micromacroporous biphasic calcium phosphate (MBCP) granules (TricOs™) or MBCP granules mixed with fibrin sealant (Tisseel®). Medial arthrotomy was performed on the knees of 20 sheep to create a bone defect (16 mm deep; 10 mm diameter), followed by anchorage of a titanium screw. Defects were filled with TricOs or TricOs–Tisseel granules, a perforated MBCP washer, a titanium washer and titanium screw. Sheep were euthanized at 3, 6, 12 and 26 weeks. From Week 12 onwards, the percentage of bone in contact with the 8 mm anchorage part of the screw increased in both groups, confirming its primary stability. At 26 weeks, whereas bone colonization was similar in both groups, biodegradation of ceramic was more rapid in the TricOs–Tisseel group (P = 0.0422). The centripetal nature of bone colonization was evident. Bone contact with the titanium implant surface was negligible. In conclusion, the use of a model that reproduces a large metaphyseal bone defect around a titanium implant with primary stability, filled with a mixture of either TricOs ceramic granules or TricOs granules mixed with Tisseel fibrin sealant, suggests that the addition of fibrin to TricOs enhances bone filling surgical technology.


Bone Defect Bone Substitute Fibrin Sealant Calcium Phosphate Cement Biphasic Calcium Phosphate 
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 study was supported by grants from ANR and RNTS, Biomatlante France and Baxter Bioscience. The authors thank C. Boucard, S. Madec, B. Pilet, and I. Pavageau for their technical assistance. We also wish to thank Maurice Bagot d’Arc of Baxter BioSurgery Europe for his helpful assistance in the management of this study.


  1. 1.
    Delmas PD, Anderson M. Launch of the bone and joint decade 2000–2010. Osteoporos Int. 2000;11:95–7.CrossRefPubMedGoogle Scholar
  2. 2.
    Jarcho M. Calcium phosphate ceramics as hard tissue prosthetics. Clin Orthop. 1981;157:259–78.PubMedGoogle Scholar
  3. 3.
    De Groot K. Ceramics of calcium phosphate: preparation and properties. In: Bioceramics of calcium phosphates. Boca Raton: CRC Press; 1983. p. 100–14.Google Scholar
  4. 4.
    Aoki H, Kato K. Application of apatite to biomaterials. Jpn Ceram Soc. 1975;10:469–78.Google Scholar
  5. 5.
    Metsger SD, Driskell TD, Paulsrud JR. Tricalcium phosphate ceramic: a resorbable bone implant: review and current uses. J Am Dent Assoc. 1982;105:1035–48.PubMedGoogle Scholar
  6. 6.
    LeGeros RZ. Calcium phosphate materials in restorative dentistry. Adv Dent Res. 1988;2:164–83.PubMedGoogle Scholar
  7. 7.
    LeGeros RZ, Nery E, Daculsi G, Lynch K, Kerebel B. In vivo transformation of biphasic calcium phosphate of varying b-TCP/HA ratios: ultrastructural characterization. In: Third world biomaterials congress; 1988 (abstract no. 35).Google Scholar
  8. 8.
    Daculsi G, LeGeros RZ, Nery E, Lynch K, Kerebel B. Transformation of biphasic calcium phosphate ceramics: ultrastructural and physico-chemical characterization. J Biomed Mater Res. 1989;23:883–94.CrossRefPubMedGoogle Scholar
  9. 9.
    LeGeros RZ, Daculsi G. In vivo transformation of biphasic calcium phosphate ceramics: ultrastructural and physicochemical characterization. In: Yamamuro N, Hench L, Wilson J, editors. Handbook of bioactive ceramics, vol 2. Boca Raton: CRC Press; 1990. p. 1728.Google Scholar
  10. 10.
    Daculsi G, Passuti N. Effect of macroporosity for osseous substitution of calcium phosphate ceramic. Biomaterials. 1990;11:86–7.PubMedGoogle Scholar
  11. 11.
    Daculsi G, Passuti N, Martin S, Deudon C, LeGeros RZ. Macroporous calcium phosphate ceramic for long bone surgery in human and dogs. J Biomed Mater Res. 1990;24:379–96.CrossRefPubMedGoogle Scholar
  12. 12.
    Bagot d’Arc M, Daculsi G, Emam N. Biphasic ceramics and fibrin sealant for bone reconstruction in ear surgery. Ann Otol Rhinol Laryngol. 2004;113:711–20.PubMedGoogle Scholar
  13. 13.
    Trecant M, Delecrin J, Royer J, Goyenvalle E, Daculsi G. Mechanical changes in macroporous calcium phosphate ceramics after implantation in bone. Clin Mater. 1994;15:233–40.CrossRefGoogle Scholar
  14. 14.
    Nery EB, LeGeros RZ, Lynch KL, Kalbfleisch J. Tissue response to biphasic calcium phosphate ceramic with different ratios of HA/β-TCP in periodontal osseous defects. J Periodontol. 1992;63:729–35.PubMedGoogle Scholar
  15. 15.
    Gouin F, Delecrin J, Passuti N, Touchais S, Poirier P, Bainvel JV. Comblement osseux par céramique phosphocalcique biphasée macroporeuse: a propos de 23 cas. Rev Chir Orthop. 1995;81:59–65. [In French].PubMedGoogle Scholar
  16. 16.
    Ransford AO, Morley T, Edgar MA, Webb P, Passuti N, Chopin D, et al. Synthetic porous ceramic compared with autograft in scoliosis surgery A prospective, randomized study of 341 patients. J Bone Joint Surg Br. 1998;80:13–8.CrossRefPubMedGoogle Scholar
  17. 17.
    Cavagna R, Daculsi G, Bouler J-M. Macroporous biphasic calcium phosphate: a prospective study of 106 cases in lumbar spine fusion. J Long Term Eff Med Implants. 1999;9:403–12.PubMedGoogle Scholar
  18. 18.
    Soares EJC, Franca VP, Wykrota L, Stumpf S. Clinical evaluation of a new bioaceramic opthalmic implant. In: LeGeros RZ, LeGeros JP, editors. Bioceramics, vol 11. Singapore: World Scientific; 1998. p. 633–6.Google Scholar
  19. 19.
    Wykrota LL, Garrido CA, Wykrota FHI. Clinical evaluation of biphasic calcium phosphate ceramic use in orthopaedic lesions. In: LeGeros RZ, LeGeros JP, editors. Bioceramics, vol 11. Singapore: World Scientific; 1998. p. 641–4.Google Scholar
  20. 20.
    Malard O, Guicheux J, Bouler J-M, et al. Calcium phosphate scaffold and bone marrow for bone reconstruction in irradiated area: a dog study. Bone. 2005;36:323–30.CrossRefPubMedGoogle Scholar
  21. 21.
    Passuti N, Delecrin J, Daculsi G. Bone substitution for spine fusion. In: Williams DF, Christel P, editors. Implants in orthopaedic surgery. Kent, England: Edward Arnold; 1992.Google Scholar
  22. 22.
    Delecrin J, Takahashi S, Gouin F, Passuti N. A synthetic porous ceramic as a bone graft substitute in the surgical management of scoliosis: a prospective, randomized study. Spine. 2000;25:563–9.CrossRefPubMedGoogle Scholar
  23. 23.
    Daculsi G. Biphasic calcium phosphate concept applied to artificial bone, implant coating and injectable bone substitute. Biomaterials. 1998;19:1473–8.CrossRefPubMedGoogle Scholar
  24. 24.
    Daculsi G, Laboux O, Malard O, Weiss P. Current state of the art of biphasic calcium phosphate bioceramics. J Mater Sci Mater Med. 2003;14:195–200.CrossRefPubMedGoogle Scholar
  25. 25.
    Daculsi G. Biphasic calcium phosphate granules concept for injectable and mouldable bone substitute. In: Advances in acience and technology. Switzerland: Trans Tech Publications; 2006. p. 9–13.Google Scholar
  26. 26.
    Daculsi G, Weiss P, Bouler J-M, Gauthier O, Aguado E. Biphasic calcium phosphate hydrosoluble polymer composites: a new concept for bone and dental substitution biomaterials. Bone. 1999;25:59–61.CrossRefGoogle Scholar
  27. 27.
    Daculsi G, Khairoun I, LeGeros RZ, et al. Bone ingrowth at the expense of a novel macroporous calcium phosphate cement. Key Eng Mater. 2006;330–2:811–4.Google Scholar
  28. 28.
    Khairoun I, LeGeros RZ, Daculsi G, Bouler JM, Guicheux J, Gauthier O. Macroporous, resorbable and injectable calcium phosphate-based cements (MCPC) for bone repair, augmentation, regeneration and osteoporosis treatment; 2004. Provisional patent no. 11/054,623.Google Scholar
  29. 29.
    Daculsi G, Layrolle P. Osteoinductive properties of micro-macroporous biphasic calcium phosphate bioceramics. Key Eng Mater. 2004;254–6:1005–8.CrossRefGoogle Scholar
  30. 30.
    Le Nihouannen D, Daculsi G, Saffarzadeh A, et al. Ectopic bone formation by microporous calcium phosphate ceramic particles in sheep muscles. Bone. 2005;36:1086–93.CrossRefPubMedGoogle Scholar
  31. 31.
    Radosevich M, Goubran HI, Burnouf T. Fibrin sealant: scientific rationale, production methods, properties, and current clinical use. Vox Sang. 1997;72:133–43.CrossRefPubMedGoogle Scholar
  32. 32.
    Dunn CJ, Goa KL. Fibrin sealant: a review of its use in surgery and endoscopy. Drugs. 1999;58:863–6.CrossRefPubMedGoogle Scholar
  33. 33.
    Mosher DF, Schad PE. Cross linking of fibronectin to collagen by blood coagulation Factor XIIIa. J Clin Invest. 1979;64:781–7.CrossRefPubMedGoogle Scholar
  34. 34.
    Rousou J, Levitsky S, Gonzalez-Lavin L, et al. Randomized clinical trial of fibrin sealant in patients undergoing resternotony or reoperation after cardiac operations. A multicenter study. J Thorac Cardiovasc Surg. 1989;97:194–203.PubMedGoogle Scholar
  35. 35.
    Wittkampf AR. Fibrin glue as cement for HA-granules. J Craniomaxillofac Surg. 1989;17:179–81.PubMedGoogle Scholar
  36. 36.
    Marini E, Valdinucci F, Silvestrini G, et al. Morphological investigations on bone formation in hydroxyapatite-fibrin implants in human maxillary and mandibular bone. Cells Mater. 1994;4:231–46.Google Scholar
  37. 37.
    Helgerson SL, Seelich T, DiOrio JP, et al. Fibrin. In: Bowlin GL, Wnek G, editors. Encyclopedia of biomaterials and biomedical engineering. Informa Healthcare; 2004. p. 1–8.Google Scholar
  38. 38.
    Nakamura K, Koshino T, Saito T. Osteogenic response of the rabbit femur to a hydroxyapatite thermal decomposition product–fibrin sealant mixture. Biomaterials. 1998;19:1901–7.CrossRefPubMedGoogle Scholar
  39. 39.
    Koolwijk P, van Erck MG, de Vree WJ, et al. Cooperative effect of TNF alpha, bFGF, and VGEF on the formation of tubular structures of human microvascular endothelial cells in a fibrin matrix. Role of urokinase activity. J Cell Biol. 1996;132:1177–88.CrossRefPubMedGoogle Scholar
  40. 40.
    Takei A, Tashiro Y, Nakashima Y, Sueishi K. Effects of fibrin on the angiogenesis in vitro of bovine endothelial cells in collagen gel. In Vitro Cell Dev Biol Anim. 1995;31:467–72.CrossRefPubMedGoogle Scholar
  41. 41.
    Schmoekel H, Schense JC, Weber FE, et al. Bone healing in the rat and dog with nonglycosylated BMP-2 demonstrating low solubility in fibrin matrices. J Orthop Res. 2004;22:376–81.CrossRefPubMedGoogle Scholar
  42. 42.
    Bauer TW, Muschler GF. Bone grafts materials. An overview of the basic science. Clin Orthop Relat Res. 2000;371:10–27.CrossRefPubMedGoogle Scholar
  43. 43.
    Le Guehennec L, Goyenvalle E, Aguado E, et al. MBCP biphasic calcium phosphate granules and tissucol fibrin sealant in rabbit femoral defects: the effect of fibrin on bone ingrowth. J Mater Sci Mater Med. 2005;16:29–35.CrossRefPubMedGoogle Scholar
  44. 44.
    Le Nihouannen D, Saffarzadeh A, Gauthier O, et al. Bone tissue formation in sheep muscles induced by a biphasic calcium phosphate ceramic and fibrin glue composite. J Mater Sci Mater Med. 2008;19:667–75.CrossRefPubMedGoogle Scholar
  45. 45.
    Saffarzadeh A, Gauthier O, Bilban M, Bagot D’Arc M, Daculsi G. Comparison of two bone substitute biomaterials consisting of a mixture of fibrin sealant (Tisseel®) and MBCP (TricOs®) with autograft in sinus lift surgery in sheep. Clin Oral Implant Res. 2009;20:1133–9.CrossRefGoogle Scholar
  46. 46.
    TRICOS Resorbable Bone Substitute. Instructions for use. Available at Accessed 14 February 2010.
  47. 47.
    Kania RE, Meunier A, Hamadouche M, Sedel L, Petite H. Addition of fibrin sealant to ceramic promotes bone repair: long-term study in rabbit femoral defect model. J Biomed Mater Res. 1998;43:38–45.CrossRefPubMedGoogle Scholar
  48. 48.
    Durand M, Chauveaux D, Moinard M, et al. Tricos® and fibrin sealant combined for bone defect filling: from preclinical tests to propspective clinical study. Preliminary human data. Key Eng Mater. 2008;361–3:1335–8.CrossRefGoogle Scholar
  49. 49.
    Reppenhagen S, Raab P, Eulert J, Noth U. TRICOS bone substitute—one-year experience with fibrin sealant biomaterial composite in the use of benign bone defects [abstract]. In: Proceedings of the 2nd international conference on strategies in tissue engineering. Cytotherapy. 2006;8(Suppl 2):1–74.Google Scholar
  50. 50.
    Abiraman S, Varma HK, Umashankar PR, John A. Fibrin glue as an osteoconductive protein in a mouse model. Biomaterials. 2002;23:3023–31.CrossRefPubMedGoogle Scholar
  51. 51.
    Arnaud E, Morieux M, Wybier M, de Vernejoul MC. Potentiation of transforming growth factor (TGF-beta 1) by natural coral and fibrin in a rabbit cranioplasty model. Calcif Tissue Int. 1994;54:493–8.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • E. Goyenvalle
    • 1
    • 2
    Email author
  • E. Aguado
    • 1
    • 2
  • P. Pilet
    • 3
  • G. Daculsi
    • 1
    • 3
    • 4
  1. 1.UPSP BBToCexEcole Nationale Vétérinaire de NantesNantes Cedex 3France
  2. 2.INSERM U922LHEA Faculty of MedicineAngersFrance
  3. 3.INSERM U791, Laboratory for Osteoarticular and Dental Tissue Engineering, Faculty of Dental SurgeryNantes UniversityNantesFrance
  4. 4.INSERM CIC-IT Biomaterials, CHU BordeauxHôpital Xavier ArnozanBordeauxFrance

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