Child's Nervous System

, Volume 31, Issue 4, pp 581–587 | Cite as

Healing of rabbit calvarial critical-sized defects using autogenous bone grafts and fibrin glue

  • Olli-Pekka Lappalainen
  • Riikka Korpi
  • Marianne Haapea
  • Jarkko Korpi
  • Leena P. Ylikontiola
  • Soili Kallio-Pulkkinen
  • Willy S. Serlo
  • Petri Lehenkari
  • George K. Sándor
Original Paper



This study aimed to evaluate ossification of cranial bone defects comparing the healing of a single piece of autogenous calvarial bone representing a bone flap as in cranioplasty compared to particulated bone slurry with and without fibrin glue to represent bone collected during cranioplasty. These defect-filling materials were then compared to empty control cranial defects.


Ten White New Zealand adult male rabbits had bilateral critical-sized calvarial defects which were left either unfilled as control defects or filled with a single full-thickness piece of autogenous bone, particulated bone, or particulated bone combined with fibrin glue. The defects were left to heal for 6 weeks postoperatively before termination. CT scans of the calvarial specimens were performed. Histomorphometric assessment of hematoxylin-eosin- and Masson trichrome-stained specimens was used to analyze the proportion of new bone and fibrous tissue in the calvarial defects.


There was a statistically significant difference in both bone and soft tissue present in all the autogenous bone-grafted defect sites compared to the empty negative control defects. These findings were supported by CT scan findings. While fibrin glue combined with the particulated bone seemed to delay ossification, the healing was more complete compared to empty control non-grafted defects.


Autogenous bone grafts in various forms such as solid bone flaps or particulated bone treated with fibrin glue were associated with bone healing which was superior to the empty control defects.


Bone healing Cranial defect Bone graft CT 



The authors wish to express their sincere gratitude for the financial support provided to this project by the University of Oulu EVO Grant Fund and the ITI Foundation (ITI Grant Number 619-2009).

Conflict of interest

The authors declare that they have no conflict of interest.


  1. 1.
    Axhousten W (1956) The osteogenetic phases of regeneration of bone; a historial and experimental study. J Bone Joint Surg Am 38:593–600Google Scholar
  2. 2.
    Urist MR (1965) Bone: formation by autoinduction. Science 150(3698):893–899CrossRefPubMedGoogle Scholar
  3. 3.
    Arnett TR (2010) Acidosis, hypoxia and bone. Arch Biochem Biophys 503:103–109CrossRefPubMedGoogle Scholar
  4. 4.
    Schmitz JP, Hollinger JO (1986) The critical size defect as an experimental model for craniomandibulofacial nonunions. Clin Orthop Relat Res 205:299–308PubMedGoogle Scholar
  5. 5.
    Spicer PP, Kretlow JD, Young S et al (2012) Evaluation of bone regeneration using the rat critical size calvarial defect. Nat Protoc 7:1918–1929CrossRefPubMedCentralPubMedGoogle Scholar
  6. 6.
    Jan A, Sándor GK, Iera D (2006) Hyperbaric oxygen results in an increase in rabbit calvarial critical sized defects. Oral Surg Oral Med Oral Pathol Oral Radiol Endodont 101:144–149CrossRefGoogle Scholar
  7. 7.
    Jan A, Sándor GK, Brkovic BMB (2009) Effects of hyperbaric oxygen on grafted and non-grafted on calvarial critical-sized defects. Oral Surg Oral Med Oral Pathol Oral Radiol Endodont 107:157–163CrossRefGoogle Scholar
  8. 8.
    Humber C, Sándor GK, Davis JM et al (2010) Bone healing with an in situ formed bioresorbable PEG membrane in rabbit calvarial defects. Oral Surg Oral Med Oral Pathol Oral Radiol Endodont 109(3):372–384CrossRefGoogle Scholar
  9. 9.
    Clokie CML, Moghadam H, Jackson MT et al (2002) Closure of critical sized defects with allogenic and alloplastic bone substitutes. J Craniofac Surg 13(1):111–121CrossRefPubMedGoogle Scholar
  10. 10.
    Haddad AJ, Peel SA, Clokie CML et al (2006) Closure of rabbit calvarial critical-sized defects using protective composite allogeneic and alloplastic bone substitutes. J Craniofac Surg 17(5):926–934CrossRefPubMedGoogle Scholar
  11. 11.
    Jan A, Sándor GK, Brkovic BM et al (2010) Effects of hyperbaric oxygen on demineralized bone matrix and biphasic calcium phosphate bone substitutes. Oral Surg Oral Med Oral Pathol Oral Radiol Endodont 109(1):60–67CrossRefGoogle Scholar
  12. 12.
    Fok TCO, Jan A, Peel SA et al (2008) Hyperbaric oxygen results in an increase in vascular endothelial growth factor (VEGF) protein expression in rabbit calvarial critical sized defects. Oral Surg Oral Med Oral Pathol Oral Radiol Endodont 105:417–422CrossRefGoogle Scholar
  13. 13.
    Beaumont M, Du Val MG, Loai Y et al (2010) Monitoring angiogenesis in soft-tissue engineered constructs for calvarium bone regeneration: an in-vivo longitudinal DCE-MRI study. Nucl Med Reson Biomed 23(1):48–55Google Scholar
  14. 14.
    Sándor GK, Numminen J, Wolff J et al (2014) Adipose stem cells used to reconstruct 13 cases with cranio-maxillofacial hard-tissue defects. Stem Cells Transl Med 3:530–540CrossRefPubMedGoogle Scholar
  15. 15.
    Uygur S, Eryilmaz T, Cukurluoglu O et al (2013) Management of cranial bone defects: a reconstructive algorithm according to defect size. J Craniofac Surg 24:1606–1609CrossRefPubMedGoogle Scholar
  16. 16.
    Serlo WS, Ylikontiola LP, Vesala AL et al (2007) Effective correction of frontal cranial deformities using biodegradable fixation on the inner surface of the cranial bones during infancy. Childs Nerv Syst 23:1439–1445CrossRefPubMedGoogle Scholar
  17. 17.
    Serlo WS, Ylikontiola LP, Lähdesluoma N et al (2011) Intracranial volume increase in craniosynostosis with posterior vault cranial distraction osteogenesis. Childs Nerv Syst 27:627–634CrossRefPubMedGoogle Scholar
  18. 18.
    Lindholm TC, Clokie CML, Sàndor GK (2003) Suction trap collected cortical bone grafts used to culture bone cells to be used for increasing efficacy of bone morphogenetic proteins in tissue engineered bone substitutes. J Oral Maxillofac Surg 61(Suppl 1):74CrossRefGoogle Scholar
  19. 19.
    Langer R, Vaganti JP (1993) Tissue engineering. Science 920:260Google Scholar
  20. 20.
    Clokie CML, Sándor GK (2008) Reconstruction of 10 major mandibular defects using BMP-7 containing bioimplants. J Can Dent Assoc 74:67–72PubMedGoogle Scholar
  21. 21.
    Sándor GK, Tuovinen VJ, Wolff J et al (2013) Adipose stem cell (ASC) tissue engineered construct used to treat large anterior mandibular defect: a case report and review of the clinical application of GMP-level ASCs for bone regeneration. J Oral Maxillofac Surg 71:938–950CrossRefPubMedGoogle Scholar
  22. 22.
    Wolff J, Sándor GK, Miettinen A et al (2013) GMP-level adipose stem cells combined with computer-aided manufacturing to reconstruct mandibular ameloblastoma resection defects: experience with 3 cases. Ann Maxillofac Surg 3:114–125CrossRefPubMedCentralPubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • Olli-Pekka Lappalainen
    • 1
    • 2
  • Riikka Korpi
    • 3
  • Marianne Haapea
    • 3
  • Jarkko Korpi
    • 4
  • Leena P. Ylikontiola
    • 2
  • Soili Kallio-Pulkkinen
    • 3
  • Willy S. Serlo
    • 5
  • Petri Lehenkari
    • 1
  • George K. Sándor
    • 2
  1. 1.Department of Anatomy and Cell BiologyUniversity of OuluOuluFinland
  2. 2.Department of Oral and Maxillofacial SurgeryUniversity of OuluOuluFinland
  3. 3.Department of Diagnostic RadiologyOulu University HospitalOuluFinland
  4. 4.Department of OtolaryngologyOulu University HospitalOuluFinland
  5. 5.Department of Pediatric SurgeryOulu University HospitalOuluFinland

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