Clinical Oral Investigations

, Volume 16, Issue 2, pp 581–590 | Cite as

Beta-tricalcium phosphate/type I collagen cones with or without a barrier membrane in human extraction socket healing: clinical, histologic, histomorphometric, and immunohistochemical evaluation

  • Bozidar M. B. Brkovic
  • Hari S. Prasad
  • Michael D. Rohrer
  • George Konandreas
  • George Agrogiannis
  • Dragana Antunovic
  • George K. B. Sándor
Original Article


The aim of this study was to investigate the healing of human extraction sockets filled with β-tricalcium phosphate and type I collagen (β-TCP/Clg) cones with or without a barrier membrane. Twenty patients were divided in two groups: (A) β-TCP/Clg non-membrane and (B) β-TCP/Clg + barrier membrane. Clinical examination and biopsies from the grafted sites were collected 9 months later. Bone samples were analyzed using histomorphometry and immunohistochemistry. The horizontal dimension of the alveolar ridge was significantly reduced 9 months after socket preservation in the non-membrane group. There was bone formation with no significant differences between the two groups in the areas occupied by new bone (A = 42.4%; B = 45.3%), marrow (A = 42.7%; B = 35.7%), or residual graft (A = 9.7%; B = 12.5%). Immunohistochemistry revealed osteonectin expression in both groups. Both groups demonstrated sufficient amounts of vital bone and socket morphology to support dental implant placement after the 9-month healing period. A future trial to evaluate the alveolar outcomes at an earlier 6-month time point rather than the 9 months used in this study would be of interest.


Socket preservation Beta-tricalcium phosphate Collagen type I Barrier membrane Histomorphometry Immunohistochemistry 



This study was supported by Septodont, France, Grant No. 2207-2006.

Conflicts of interest

The authors declare that they have no conflicts of interest.


  1. 1.
    Tallgren A (2003) The continuing reduction of the residual alveolar ridge in complete denture wearers: a mixed-longitudinal study covering 25 years. J Prosthet Dent 89:427–435PubMedCrossRefGoogle Scholar
  2. 2.
    Lekovic V, Kenney EB, Weinlaender M, Han T, Klokkevold P, Nedic M, Orsini M (1997) A bone regenerative approach to alveolar ridge maintenance following tooth extraction. Report of 10 cases. J Periodontol 686:563–570Google Scholar
  3. 3.
    Schropp L, Wenzel A, Kostopoulos L, Karring T (2003) Bone healing and soft tissue contour changes following single-tooth extraction: a clinical and radiographic 12-month prospective study. Int J Periodontics Restorative Dent 23:313–323PubMedGoogle Scholar
  4. 4.
    Chen ST, Buser D (2004) Implants in post-extraction sites—a literature update. In: Buser D, Wismeijer D, Belser U (eds) ITI treatment guide. Quintessence, Berlin, pp 9–17Google Scholar
  5. 5.
    Chen ST, Wilson TG, Hämmerle CH (2004) Immediate or early placement of implants following tooth extraction: review of biologic basis, clinical procedures, and outcomes. Int J Oral Maxillofac Implants 19:12–25PubMedGoogle Scholar
  6. 6.
    Cardaropoli G, Araujo M, Hayacibara R, Sukekava F, Lindhe J (2005) Healing of extraction sockets and surgically produced—augmented and non-augmented—defects in alveolar ridge. An experimental study in the dog. J Clin Periodontol 32:435–440PubMedCrossRefGoogle Scholar
  7. 7.
    Fickl S, Zuhr O, Wachtel H, Bolz W, Huerzeler MB (2008) Hard tissue alterations after socket preservation: an experimental study in the beagle dog. Clin Oral Implants Res 19:1111–1118PubMedCrossRefGoogle Scholar
  8. 8.
    Araujo MG, Lindhe J (2005) Dimensional ridge alterations following tooth extraction: an experimental study in the dog. J Clin Periodontol 32:212–218PubMedCrossRefGoogle Scholar
  9. 9.
    Carmagnola D, Adriaens P, Berglundh T (2003) Healing of human extraction socket filled with Bio-Oss®. Clin Oral Implants Res 14:137–143PubMedCrossRefGoogle Scholar
  10. 10.
    Herberer S, Al-Chawaf B, Hildebrand D, Nelson JJ, Nelson K (2008) Histomorphometric analysis of extraction sockets augmented with Bio-Oss Collagen after a 6-week healing period: a prospective study. Clin Oral Implants Res 19:1219–1225CrossRefGoogle Scholar
  11. 11.
    Brkovic BMB, Prasad HS, Konandreas G, Radulovic M, Antunovic D, Sándor GKB, Rohrer M (2008) Simple preservation of a maxillary extraction socket using betatricalcium phosphate with type I collagen: preliminary clinical and histomorphometric observation. JCDA 74:513–518Google Scholar
  12. 12.
    Rothamel D, Schwarz F, Herten M, Engelhardt E, Donath K, Kuehn P, Becker J (2008) Dimensional ridge alterations following socket preservation using a nanocrystalline hydroxyapatite paste. A histomorphometrical study in dogs. Int J Oral Maxillofac Surg 37:741–747PubMedCrossRefGoogle Scholar
  13. 13.
    Araujo M, Linder E, Lindhe J (2008) Effect of a xenograft on early bone formation in extraction sockets: an experimental study in dog. Clin Oral Implants Res 20:1–6CrossRefGoogle Scholar
  14. 14.
    Kainulainen VT, Sándor GKB, Carmichael RP, Oikarinen KS (2005) Safety of zygomatic bone harvesting: a prospective study of 32 consecutive patients with simultaneous zygomatic bone grafting and 1-stage implant placement. Int J Oral Maxillofac Implants 20:245–252PubMedGoogle Scholar
  15. 15.
    Buser D, Dula K, Hirt HP, Schenk RK (1996) Lateral ridge augmentation using autografts and barrier membrane: a clinical study with 40 partially edentulous patients. J Oral Maxillofac Surg 54:420–432PubMedCrossRefGoogle Scholar
  16. 16.
    Clavero J, Lundgren S (2003) Ramus or chin grafts for maxillary sinus inlay and local onlay augmentation: comparison of donor site morbidity and complications. Clin Implant Dent Relat Res 5:154–160PubMedCrossRefGoogle Scholar
  17. 17.
    Giannoudis PV, Dinopoulos H, Tsiridis E (2005) Bone substitute: an update. Injury 36:S20–S27PubMedCrossRefGoogle Scholar
  18. 18.
    Zerbo IR, Bronckers ALJJ, de Lange GL, van Beek GJ, Burger EH (2001) Histology of human alveolar bone regeneration with a porous tricalcium phosphate. A report of two cases. Clin Oral Implants Res 12:379–384PubMedCrossRefGoogle Scholar
  19. 19.
    Thoma DS, Halg GA, Dard MM, Seibl R, Hämmerle CHF, Jung RE (2008) Evaluation of a new biodegradable membrane to prevent gingival ingrowth into mandibular bone defects in minipigs. Clin Oral Implants Res 20:7–16CrossRefGoogle Scholar
  20. 20.
    Aaboe M, Pinholt EM, Schou S, Hjørting-Hansen E (1998) Incomplete bone regeneration of rabbit calvarial defects using different membranes. Clin Oral Implants Res 9:313–320PubMedCrossRefGoogle Scholar
  21. 21.
    Malchiodi L, Scarano A, Quaranta M, Piattelli A (1998) Rigid fixation by means of titanium mesh in edentulous ridge expansion for horizontal ridge augmentation in the maxilla. Int J Oral Maxillofac Implants 13:701–705PubMedGoogle Scholar
  22. 22.
    Zitzmann NU, Scharer P, Marinello CP (2001) Long-term results of implants treated with guided bone regeneration: a 5-years prospective study. Int J Oral Maxillofac Implants 16:355–366PubMedGoogle Scholar
  23. 23.
    Artzi Z, Dayan D, Alpern Y, Nemcovsky CE (2003) Vertical ridge augmentation using xenogenic material supported by a configured titanium mesh: clinicohistopathologic and histochemical study. Int J Oral Maxillofac Implants 18:440–446PubMedGoogle Scholar
  24. 24.
    Strietzel FP, Khongkhunthian P, Khattiya R, Patchanee P, Reichart PA (2006) Healing pattern of bone defects covered by different membrane types—a histologic study in the porcine mandible. J Biomed Mater Res B Appl Biomater 78:35–46PubMedGoogle Scholar
  25. 25.
    Fujita R, Yokoyama A, Nodasaka Y, Kohgo T, Kawasaki T (2003) Ultrastructure of ceramic–bone interface using hydroxyapatite and β-tricalcium phosphate ceramics and replacement mechanism of β-tricalcium phosphate in bone. Tissue Cell 35:427–440PubMedCrossRefGoogle Scholar
  26. 26.
    Artzi Z, Weinreb M, Givol N, Rohrer M, Nemcovsky CE, Prasad HS, Tal H (2004) Biomaterial resorption rate and healing site morphology of inorganic bovine bone and β-tricalcium phosphate in the canine: a 24-month longitudinal histologic study and morphometric analysis. Int J Oral Maxillofac Implants 19:357–368PubMedGoogle Scholar
  27. 27.
    Jensen SS, Broggini N, Hjørting-Hansen E, Schenk R, Buser D (2006) Bone healing and graft resorption of autograft, anorganic bovine bone and β-tricalcium phosphate. A histologic and histomorphometric study in the mandible of minipigs. Clin Oral Implants Res 17:237–243PubMedCrossRefGoogle Scholar
  28. 28.
    Schwarz F, Herten M, Ferrari D, Wieland M, Schmitz L, Engelhardt E, Becker J (2007) Guided bone regeneration at dehiscence-type defects using biphasic hydroxyapatite + beta tricalcium phosphate (Bone Ceramic®) or a collagen-coated natural bone mineral (BioOss Collagen®): an immunohistochemical study in dogs. Int J Oral Maxillofac Surg 36:1198–1206PubMedCrossRefGoogle Scholar
  29. 29.
    Thompson DM, Rohrer MD, Prasad HS (2006) Comparison of bone grafting materials in human extraction sockets: clinical, histologic, and histomorphometric evaluation. Implant Dent 15:89–96PubMedCrossRefGoogle Scholar
  30. 30.
    Zijderveld SA, Zerbo IR, van den Bergh JPA, Schulten EAJM, ten Bruggenkate CM (2005) Maxillary sinus floor augmentation using a β-tricalcium phosphate (Cerasorb) alone compared to autogenous bone graft. Int J Oral Maxillofac Implants 20:432–440PubMedGoogle Scholar
  31. 31.
    Wiltfang J, Schlegel KA, Schultze-Mosgau S, Nkenke E, Zimmermann R, Kessler P (2003) Sinus floor augmentation with beta-tricalciumphosphate (beta-TCP): does platelet-rich plasma promote its osseous integration and degradation? Clin Oral Implant Res 14:213–218CrossRefGoogle Scholar
  32. 32.
    Zou C, Weng W, Deng X, Cheng K, Liu X, Du P, Shen G, Han G (2005) Preparation and characterization of porous beta-tricalcium phosphate/collagen composites with an integrated structure. Biomaterials 26:5276–5284PubMedCrossRefGoogle Scholar
  33. 33.
    Simunek A, Clerny M, Kopecka D, Kohout A, Bukac J, Vahalova D (2005) Sinus lift with phycogenic bone substitute. A histomorphometric study. Clin Oral Implants Res 16:342–348PubMedCrossRefGoogle Scholar
  34. 34.
    Pioletti DP, Takei H, Lin T, Van Landuyt P, Ma QJ, Kwon SY, Sung KL (2000) The effects of calcium phosphate cement particles on osteoblast function. Biomaterials 21:1103–1114PubMedCrossRefGoogle Scholar
  35. 35.
    Zerbo IR, Bronckers AL, de Lange G, Burger EH (2005) Localization of osteogenic cells and osteoplastic cells in porous beta-tricalcium phosphate particles used for human maxillary sinus floor elevation. Biomaterials 26:1445–1451PubMedCrossRefGoogle Scholar
  36. 36.
    Cardaropoli G, Araujo M, Lindhe J (2003) Dynamic of bone tissue formation in tooth extraction sites. An experimental study in dogs. J Clin Periodontol 30:809–818PubMedCrossRefGoogle Scholar
  37. 37.
    Amler MH (1969) The time sequence of tissue regeneration in human extraction wounds. Oral Surg Oral Med Oral Pathol 27:309–318PubMedCrossRefGoogle Scholar
  38. 38.
    Szabό G, Huys L, Coulthard P, Maiorana C, Garagiola U, Barabás J, Németh Z, Hrabak K, Suba Z (2005) A prospective multicenter randomized clinical trial of autogenous bone versus β-tricalcium phosphate graft alone for bilateral sinus elevation: histologic and histomorphometric evaluation. Int J Oral Maxillofac Implants 20:371–381Google Scholar
  39. 39.
    Simunek A, Kopecka D, Somanatha RV, Pilathatka S, Brazda T (2008) Deproteinized bovine bone versus β-tricalcium phosphate in sinus augmentation surgery: a comparative histologic and histomorphometric study. Int J Oral Maxillofac Implants 23:935–942PubMedGoogle Scholar
  40. 40.
    Lu J, Descamps M, Dejou J, Koubi G, Hardouin P, Lemaitre J, Proust JP (2002) The biodegradation mechanism of calcium phosphate biomaterials in bone. J Biomed Mater Res 63:408–412PubMedCrossRefGoogle Scholar
  41. 41.
    Merten HA, Wiltfang J, Grohmann U, Hoenig JF (2001) Intraindividual comparative animal study of alpha- and beta-tricalcium phosphate degradation in conjunction with simultaneous insertion of dental implants. J Craniofac Surg 12:59–68PubMedCrossRefGoogle Scholar
  42. 42.
    Glowacki J, Schulten AJ, Perrott D, Kaban LB (2008) Nicotine impairs distraction osteogenesis in the rat mandible. Int J Oral Maxillofac Surg 37:156–161PubMedCrossRefGoogle Scholar
  43. 43.
    Horch HH, Sader R, Pautke C, Neff A, Deppe H, Kolk A (2006) Synthetic, pure-phase beta-tricalcium phosphate ceramic granules (Cerasorb®) for bone regeneration in the reconstructive surgery of the jaws. Int J Oral Maxillofac Surg 35:708–713PubMedCrossRefGoogle Scholar
  44. 44.
    Termine JD, Kleinman HK, Whitson SW, Conn KM, McGarvey ML, Martin GR (1981) Osteonectin, a bone-specific protein linking mineral to collagen. Cell 26:99–105PubMedCrossRefGoogle Scholar
  45. 45.
    Hu ZM, Peel SA, Ho SK, Sàndor GKB, Clokie CM (2005) Role of bovine bone morphogenetic proteins in bone matrix protein and osteoblast-related gene expression during rat bone marrow stromal cell differentiation. J Craniofac Surg 16(6):1006–1014PubMedCrossRefGoogle Scholar
  46. 46.
    Brägger U, Pasqualli L, Kornman KS (1988) Remodeling of interdental alveolar bone after periodontal flap procedure assessed by means of computer-assisted densitometer image analysis (CADIA). J Clin Periodontol 15:558–564PubMedCrossRefGoogle Scholar
  47. 47.
    Iasella JM, Greenwell H, Miller RL, Hill M, Drisko C, Bohra AA, Scheetze JP (2003) Ridge preservation with freeze-dried bone allograft and a collagen membrane compared to extraction alone for implant site development: a clinical and histologic study in humans. J Periodontol 74:990–999PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • Bozidar M. B. Brkovic
    • 1
  • Hari S. Prasad
    • 2
  • Michael D. Rohrer
    • 2
    • 3
  • George Konandreas
    • 4
  • George Agrogiannis
    • 5
  • Dragana Antunovic
    • 6
  • George K. B. Sándor
    • 7
    • 8
  1. 1.Clinic of Oral Surgery, Faculty of DentistryUniversity of BelgradeBelgradeSerbia
  2. 2.Hard Tissue Research Laboratory, School of DentistryUniversity of MinnesotaMinneapolisUSA
  3. 3.Division of Oral Pathology, School of DentistryUniversity of MinnesotaMinneapolisUSA
  4. 4.AthensGreece
  5. 5.Department of Pathology, School of MedicineNational and Kapodistrian University of AthensAthensGreece
  6. 6.BelgradeSerbia
  7. 7.Tissue Engineering, Regea Institute for Regenerative MedicineUniversity of TampereTampereFinland
  8. 8.Department of Oral and Maxillofacial SurgeryUniversity of OuluOuluFinland

Personalised recommendations