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Investigation of a pre-clinical mandibular bone notch defect model in miniature pigs: clinical computed tomography, micro-computed tomography, and histological evaluation

  • Carlisle, Patricia L. (Department of Craniomaxillofacial Regenerative Medicine, The United States Army Dental and Trauma Research Detachment) ;
  • Guda, Teja (Department of Craniomaxillofacial Regenerative Medicine, The United States Army Dental and Trauma Research Detachment) ;
  • Silliman, David T. (Department of Craniomaxillofacial Regenerative Medicine, The United States Army Dental and Trauma Research Detachment) ;
  • Lien, Wen (Department of Craniomaxillofacial Regenerative Medicine, The United States Army Dental and Trauma Research Detachment) ;
  • Hale, Robert G. (Department of Craniomaxillofacial Regenerative Medicine, The United States Army Dental and Trauma Research Detachment) ;
  • Baer, Pamela R. Brown (Department of Craniomaxillofacial Regenerative Medicine, The United States Army Dental and Trauma Research Detachment)
  • Received : 2015.10.15
  • Accepted : 2015.12.29
  • Published : 2016.02.29

Abstract

Objectives: To validate a critical-size mandibular bone defect model in miniature pigs. Materials and Methods: Bilateral notch defects were produced in the mandible of dentally mature miniature pigs. The right mandibular defect remained untreated while the left defect received an autograft. Bone healing was evaluated by computed tomography (CT) at 4 and 16 weeks, and by micro-CT and non-decalcified histology at 16 weeks. Results: In both the untreated and autograft treated groups, mineralized tissue volume was reduced significantly at 4 weeks post-surgery, but was comparable to the pre-surgery levels after 16 weeks. After 16 weeks, CT analysis indicated that significantly greater bone was regenerated in the autograft treated defect than in the untreated defect (P=0.013). Regardless of the treatment, the cortical bone was superior to the defect remodeled over 16 weeks to compensate for the notch defect. Conclusion: The presence of considerable bone healing in both treated and untreated groups suggests that this model is inadequate as a critical-size defect. Despite healing and adaptation, the original bone geometry and quality of the pre-injured mandible was not obtained. On the other hand, this model is justified for evaluating accelerated healing and mitigating the bone remodeling response, which are both important considerations for dental implant restorations.

Keywords

References

  1. Mitchener TA, Canham-Chervak M. Oral-maxillofacial injury surveillance in the Department of Defense, 1996-2005. Am J Prev Med 2010;38(1 Suppl):S86-93. https://doi.org/10.1016/j.amepre.2009.10.016
  2. Lew TA, Walker JA, Wenke JC, Blackbourne LH, Hale RG. Characterization of craniomaxillofacial battle injuries sustained by United States service members in the current conflicts of Iraq and Afghanistan. J Oral Maxillofac Surg 2010;68:3-7. https://doi.org/10.1016/j.joms.2009.06.006
  3. Owens BD, Kragh JF Jr, Wenke JC, Macaitis J, Wade CE, Holcomb JB. Combat wounds in operation Iraqi freedom and operation enduring freedom. J Trauma 2008;64:295-9. https://doi.org/10.1097/TA.0b013e318163b875
  4. Rachmiel A, Srouji S, Peled M. Alveolar ridge augmentation by distraction osteogenesis. Int J Oral Maxillofac Surg 2001;30:510-7. https://doi.org/10.1054/ijom.2001.0134
  5. Petrovic V, Zivkovic P, Petrovic D, Stefanovic V. Craniofacial bone tissue engineering. Oral Surg Oral Med Oral Pathol Oral Radiol 2012;114:e1-9. https://doi.org/10.1016/S2212-4403(12)01655-0
  6. Brown Baer PR, Wenke JC, Thomas SJ, Hale CR. Investigation of severe craniomaxillofacial battle injuries sustained by u.s. Service members: a case series. Craniomaxillofac Trauma Reconstr 2012;5: 243-52. https://doi.org/10.1055/s-0032-1329542
  7. Bahat O, Fontanesi RV, Preston J. Reconstruction of the hard and soft tissues for optimal placement of osseointegrated implants. Int J Periodontics Restorative Dent 1993;13:255-75.
  8. Lekholm U, Zarb GA. Patient selection and preparation. In: Branemark PI, Zarb GA, Albrektsson T, eds. Tissue-integrated prostheses: osseointegration in clinical dentistry. Chicago: Quintessence Publishing; 1985:199-209.
  9. Nasser M, Pandis N, Fleming PS, Fedorowicz Z, Ellis E, Ali K. Interventions for the management of mandibular fractures. Cochrane Database Syst Rev 2013;7:CD006087.
  10. Zakhary IE, El-Mekkawi HA, Elsalanty ME. Alveolar ridge augmentation for implant fixation: status review. Oral Surg Oral Med Oral Pathol Oral Radiol 2012;114(5 Suppl):S179-89. https://doi.org/10.1016/j.oooo.2011.09.031
  11. Reichert JC, Saifzadeh S, Wullschleger ME, Epari DR, Schutz MA, Duda GN, et al. The challenge of establishing preclinical models for segmental bone defect research. Biomaterials 2009;30:2149-63. https://doi.org/10.1016/j.biomaterials.2008.12.050
  12. Fennis JP, Stoelinga PJ, Jansen JA. Mandibular reconstruction: a clinical and radiographic animal study on the use of autogenous scaffolds and platelet-rich plasma. Int J Oral Maxillofac Surg 2002;31:281-6. https://doi.org/10.1054/ijom.2002.0151
  13. Fennis JP, Stoelinga PJ, Jansen JA. Mandibular reconstruction: a histological and histomorphometric study on the use of autogenous scaffolds, particulate cortico-cancellous bone grafts and platelet rich plasma in goats. Int J Oral Maxillofac Surg 2004;33:48-55. https://doi.org/10.1054/ijom.2003.0452
  14. Fennis JP, Stoelinga PJ, Jansen JA. Reconstruction of the mandible with an autogenous irradiated cortical scaffold, autogenous corticocancellous bone-graft and autogenous platelet-rich-plasma: an animal experiment. Int J Oral Maxillofac Surg 2005;34:158-66.
  15. Salmon R, Duncan W. Determination of the critical size for nonhealing defects in the mandibular bone of sheep. Part 1: a pilot study. J N Z Soc Periodontol 1997;(81):6-15.
  16. Marshall J, Duncan W. Determination of the critical size for nonhealing defects in the mandibular bone of sheep. Part 2: healing of 12 mm circular defects after 16 weeks. J N Z Soc Periodontol 1997;(82):6-10.
  17. Ayoub A, Challa SR, Abu-Serriah M, McMahon J, Moos K, Creanor S, et al. Use of a composite pedicled muscle flap and rh-BMP-7 for mandibular reconstruction. Int J Oral Maxillofac Surg 2007;36:1183-92. https://doi.org/10.1016/j.ijom.2007.07.012
  18. Abu-Serriah M, Kontaxis A, Ayoub A, Harrison J, Odell E, Barbenel J. Mechanical evaluation of mandibular defects reconstructed using osteogenic protein-1 (rhOP-1) in a sheep model: a critical analysis. Int J Oral Maxillofac Surg 2005;34:287-93. https://doi.org/10.1016/j.ijom.2004.09.008
  19. Abu-Serriah MM, Odell E, Lock C, Gillar A, Ayoub AF, Fleming RH. Histological assessment of bioengineered new bone in repairing osteoperiosteal mandibular defects in sheep using recombinant human bone morphogenetic protein-7. Br J Oral Maxillofac Surg 2004;42:410-8.
  20. Gerard D, Carlson ER, Gotcher JE, Jacobs M. Effects of plateletrich plasma on the healing of autologous bone grafted mandibular defects in dogs. J Oral Maxillofac Surg 2006;64:443-51. https://doi.org/10.1016/j.joms.2005.11.016
  21. Gerard D, Carlson ER, Gotcher JE, Jacobs M. Effects of plateletrich plasma at the cellular level on healing of autologous bonegrafted mandibular defects in dogs. J Oral Maxillofac Surg 2007;65:721-7. https://doi.org/10.1016/j.joms.2006.09.025
  22. Messora MR, Nagata MJ, Pola NM, de Campos N, Fucini SE, Furlaneto FA. Effect of platelet-rich plasma on bone healing of fresh frozen bone allograft in mandibular defects: a histomorphometric study in dogs. Clin Oral Implants Res 2013;24:1347-53. https://doi.org/10.1111/clr.12008
  23. Hollinger JO, Kleinschmidt JC. The critical size defect as an experimental model to test bone repair materials. J Craniofac Surg 1990;1:60-8. https://doi.org/10.1097/00001665-199001000-00011
  24. 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. https://doi.org/10.22203/eCM.v013a01
  25. Wang S, Liu Y, Fang D, Shi S. The miniature pig: a useful large animal model for dental and orofacial research. Oral Dis 2007;13:530-7. https://doi.org/10.1111/j.1601-0825.2006.01337.x
  26. Jeong HR, Hwang JH, Lee JK. Effectiveness of autogenous tooth bone used as a graft material for regeneration of bone in miniature pig. J Korean Assoc Oral Maxillofac Surg 2011;37:375-9. https://doi.org/10.5125/jkaoms.2011.37.5.375
  27. Henkel KO, Gerber T, Dietrich W, Bienengraber V. Novel calcium phosphate formula for filling bone defects. Initial in vivo long-term results. Mund Kiefer Gesichtschir 2004;8:277-81. https://doi.org/10.1007/s10006-004-0561-9
  28. Henkel KO, Gerber T, Lenz S, Gundlach KK, Bienengraber V. Macroscopical, histological, and morphometric studies of porous bone-replacement materials in minipigs 8 months after implantation. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2006;102: 606-13. https://doi.org/10.1016/j.tripleo.2005.10.034
  29. Ruehe B, Niehues S, Heberer S, Nelson K. Miniature pigs as an animal model for implant research: bone regeneration in criticalsize defects. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2009;108:699-706. https://doi.org/10.1016/j.tripleo.2009.06.037
  30. Ma JL, Pan JL, Tan BS, Cui FZ. Determination of critical size defect of minipig mandible. J Tissue Eng Regen Med 2009;3:615-22. https://doi.org/10.1002/term.203
  31. Schneider CA, Rasband WS, Eliceiri KW. NIH Image to ImageJ: 25 years of image analysis. Nat Methods 2012;9:671-5. https://doi.org/10.1038/nmeth.2089
  32. Otsu N. A threshold selection method from gray-level histograms. Automatica 1975;11:23-7.
  33. Strietzel FP, Khongkhunthian P, Khattiya R, Patchanee P, Reichart PA. Healing pattern of bone defects covered by different membrane types--a histologic study in the porcine mandible. J Biomed Mater Res B Appl Biomater 2006;78:35-46.
  34. Jensen SS, Bornstein MM, Dard M, Bosshardt DD, Buser D. Comparative study of biphasic calcium phosphates with different HA/ TCP ratios in mandibular bone defects: a long-term histomorphometric study in minipigs. J Biomed Mater Res B Appl Biomater 2009;90:171-81.
  35. Jensen SS, Broggini N, Hjorting-Hansen E, Schenk R, Buser D. Bone healing and graft resorption of autograft, anorganic bovine bone and beta-tricalcium phosphate: a histologic and histomorphometric study in the mandibles of minipigs. Clin Oral Implants Res 2006;17:237-43. https://doi.org/10.1111/j.1600-0501.2005.01257.x
  36. Abukawa H, Shin M, Williams WB, Vacanti JP, Kaban LB, Troulis MJ. Reconstruction of mandibular defects with autologous tissueengineered bone. J Oral Maxillofac Surg 2004;62:601-6. https://doi.org/10.1016/j.joms.2003.11.010
  37. Groger A, Klaring S, Merten HA, Holste J, Kaps C, Sittinger M. Tissue engineering of bone for mandibular augmentation in immunocompetent minipigs: preliminary study. Scand J Plast Reconstr Surg Hand Surg 2003;37:129-33. https://doi.org/10.1080/02844310310007728
  38. Coen Pramono D. Spontaneous bone regeneration after mandible resection in a case of ameloblastoma: a case report. Ann Acad Med Singapore 2004;33(4 Suppl):59-62.
  39. Ihan Hren N, Miljavec M. Spontaneous bone healing of the large bone defects in the mandible. Int J Oral Maxillofac Surg 2008;37: 1111-6. https://doi.org/10.1016/j.ijom.2008.07.008
  40. Ogunlewe MO, Akinwande JA, Ladeinde AL, Adeyemo WL. Spontaneous regeneration of whole mandible after total mandibulectomy in a sickle cell patient. J Oral Maxillofac Surg 2006;64:981-4. https://doi.org/10.1016/j.joms.2006.02.008
  41. Zambon R, Mardas N, Horvath A, Petrie A, Dard M, Donos N. The effect of loading in regenerated bone in dehiscence defects following a combined approach of bone grafting and GBR. Clin Oral Implants Res 2012;23:591-601. https://doi.org/10.1111/j.1600-0501.2011.02279.x
  42. Orsini G, Scarano A, Piattelli M, Piccirilli M, Caputi S, Piattelli A. Histologic and ultrastructural analysis of regenerated bone in maxillary sinus augmentation using a porcine bone-derived biomaterial. J Periodontol 2006;77:1984-90. https://doi.org/10.1902/jop.2006.060181
  43. Miron RJ, Gruber R, Hedbom E, Saulacic N, Zhang Y, Sculean A, et al. Impact of bone harvesting techniques on cell viability and the release of growth factors of autografts. Clin Implant Dent Relat Res 2013;15:481-9. https://doi.org/10.1111/j.1708-8208.2012.00440.x
  44. Liu W, Tang XJ, Zhang ZY, Yin L, Gui L. 3D-CT evaluation of mandibular morphology after mandibular outer cortex osteotomy in young miniature pigs: the role of the periosteum. J Craniomaxillofac Surg 2014;42:763-71. https://doi.org/10.1016/j.jcms.2013.11.008
  45. Van der Weijden F, Dell'Acqua F, Slot DE. Alveolar bone dimensional changes of post-extraction sockets in humans: a systematic review. J Clin Periodontol 2009;36:1048-58. https://doi.org/10.1111/j.1600-051X.2009.01482.x

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