Journal of Periodontal and Implant Science

Korean Academy of Periodontology (대한치주과학회)
권호 표지
DOI QR코드

DOI QR Code

Novel analysis model for implant osseointegration using ectopic bone formation via the recombinant human bone morphogenetic protein-2/macroporous biphasic calcium phosphate block system in rats: a proof-of-concept study

  • Park, Jung-Chul (Department of Periodontology, Research Institute for Periodontal Regeneration, Yonsei University College of Dentistry) ;
  • Lee, Jong-Bin (Department of Periodontology, Research Institute for Periodontal Regeneration, Yonsei University College of Dentistry) ;
  • Daculsi, Guy (Research Center on Materials of Biological Interest, Dental faculty, Nantes University) ;
  • Oh, Sang-Yeop (Department of Periodontology, Research Institute for Periodontal Regeneration, Yonsei University College of Dentistry) ;
  • Cho, Kyoo-Sung (Department of Periodontology, Research Institute for Periodontal Regeneration, Yonsei University College of Dentistry) ;
  • Im, Gun-Il (Department of Orthopedics, Dongguk University Ilsan Hospital) ;
  • Kim, Byung-Soo (School of Chemical and Biological Engineering, Seoul National University) ;
  • Kim, Chang-Sung (Department of Periodontology, Research Institute for Periodontal Regeneration, Yonsei University College of Dentistry)
  • Received : 2012.04.21
  • Accepted : 2012.06.12
  • Published : 2012.08.31
Download PDF
⟨ Previous Next ⟩

Abstract

Purpose: The osseointegration around titanium mini-implants installed in macroporous biphasic calcium phosphate (MBCP) blocks was evaluated after incubation with recombinant human bone morphogenetic protein-2 (rhBMP-2) in an ectopic subcutaneous rat model. Methods: Mini-implants (${\varphi}1.8{\times}12$ mm) were installed in MBCP blocks (bMBCPs, $4{\times}5{\times}15$ mm) loaded with rhBMP-2 at 0.1 mg/mL, and then implanted for 8 weeks into subcutaneous pockets of male Sprague-Dawley rats (n=10). A histomorphometric analysis was performed, and the bone-to-implant contact (BIC) and bone density were evaluated. Results: Significant osteoinductive activity was induced in the rhBMP-2/bMBCP group. The percentage of BIC was $41.23{\pm}4.13%$ (mean${\pm}$standard deviation), while bone density was $33.47{\pm}5.73%$. In contrast, no bone formation was observed in the bMBCP only group. Conclusions: This model represents a more standardized tool for analyzing osseointegration and bone healing along the implant surface and in bMBCPs that excludes various healing factors derived from selected animals and defect models.

Keywords

References

  1. Wikesjo UM, Guglielmoni P, Promsudthi A, Cho KS, Trombelli L, Selvig KA, et al. Periodontal repair in dogs: effect of rhBMP-2 concentration on regeneration of alveolar bone and periodontal attachment. J Clin Periodontol 1999;26: 392-400.
  2. Blumenthal NM, Koh-Kunst G, Alves ME, Miranda D, Sorensen RG, Wozney JM, et al. Effect of surgical implantation of recombinant human bone morphogenetic protein-2 in a bioabsorbable collagen sponge or calcium phosphate putty carrier in intrabony periodontal defects in the baboon. J Periodontol 2002;73:1494-1506.
  3. Boyne PJ, Nath R, Nakamura A. Human recombinant BMP-2 in osseous reconstruction of simulated cleft palate defects. Br J Oral Maxillofac Surg 1998;36:84-90.
  4. Barboza EP, Duarte ME, Geolas L, Sorensen RG, Riedel GE, Wikesjo UM. Ridge augmentation following implantation of recombinant human bone morphogenetic protein-2 in the dog. J Periodontol 2000;71:488-496.
  5. Jung JH, Yun JH, Um YJ, Jung UW, Kim CS, Choi SH, et al. Bone formation of Escherichia coli expressed rhBMP-2 on absorbable collagen block in rat calvarial defects. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2011;111: 298-305.
  6. Jang JW, Yun JH, Lee KI, Jang JW, Jung UW, Kim CS, et al. Osteoinductive activity of biphasic calcium phosphate with different rhBMP-2 doses in rats. Oral Surg Oral Med Oral Pathol Oral Radiol 2012;113:480-487.
  7. Kim CS, Kim JI, Kim J, Choi SH, Chai JK, Kim CK, et al. Ectopic bone formation associated with recombinant human bone morphogenetic proteins-2 using absorbable collagen sponge and beta tricalcium phosphate as carriers. Biomaterials 2005;26:2501-2507.
  8. Jung RE, Glauser R, Scharer P, Hammerle CH, Sailer HF, Weber FE. Effect of rhBMP-2 on guided bone regeneration in humans. Clin Oral Implants Res 2003;14:556-568.
  9. Smeets R, Maciejewski O, Gerressen M, Spiekermann H, Hanisch O, Riediger D, et al. Impact of rhBMP-2 on regeneration of buccal alveolar defects during the osseointegration of transgingival inserted implants. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2009;108:e3-e12.
  10. Wikesjo UM, Sorensen RG, Wozney JM. Augmentation of alveolar bone and dental implant osseointegration: clinical implications of studies with rhBMP-2. J Bone Joint Surg Am 2001;83 Suppl 1(Pt 2):S136-S145.
  11. Nevins M, Kirker-Head C, Nevins M, Wozney JA, Palmer R, Graham D. Bone formation in the goat maxillary sinus induced by absorbable collagen sponge implants impregnated with recombinant human bone morphogenetic protein-2. Int J Periodontics Restorative Dent 1996;16:8-19.
  12. Lekholm U, Adell R, Lindhe J, Branemark PI, Eriksson B, Rockler B, et al. Marginal tissue reactions at osseointegrated titanium fixtures. (II) A cross-sectional retrospective study. Int J Oral Maxillofac Surg 1986;15:53-61.
  13. Hall J, Sorensen RG, Wozney JM, Wikesjo UM. Bone formation at rhBMP-2-coated titanium implants in the rat ectopic model. J Clin Periodontol 2007;34:444-451.
  14. Herr G, Hartwig CH, Boll C, Kusswetter W. Ectopic bone formation by composites of BMP and metal implants in rats. Acta Orthop Scand 1996;67:606-610.
  15. Wikesjo UM, Qahash M, Polimeni G, Susin C, Shanaman RH, Rohrer MD, et al. Alveolar ridge augmentation using implants coated with recombinant human bone morphogenetic protein-2: histologic observations. J Clin Periodontol 2008;35:1001-1010.
  16. Lee J, Decker JF, Polimeni G, Cortella CA, Rohrer MD, Wozney JM, et al. Evaluation of implants coated with rhBMP-2 using two different coating strategies: a critical-size supraalveolar peri-implant defect study in dogs. J Clin Periodontol 2010;37:582-590.
  17. Susin C, Qahash M, Polimeni G, Lu PH, Prasad HS, Rohrer MD, et al. Alveolar ridge augmentation using implants coated with recombinant human bone morphogenetic protein-7 (rhBMP-7/rhOP-1): histological observations. J Clin Periodontol 2010;37:574-581.
  18. Wikesjo UM, Susin C, Qahash M, Polimeni G, Leknes KN, Shanaman RH, et al. The critical-size supraalveolar peri-implant defect model: characteristics and use. J Clin Periodontol 2006;33:846-854.
  19. Tatakis DN, Koh A, Jin L, Wozney JM, Rohrer MD, Wikesjo UM. Peri-implant bone regeneration using recombinant human bone morphogenetic protein-2 in a canine model: a dose-response study. J Periodontal Res 2002;37:93-100.
  20. Decker JF, Lee J, Cortella CA, Polimeni G, Rohrer MD, Wozney JM, et al. Evaluation of implants coated with recombinant human bone morphogenetic protein-2 and vacuum-dried using the critical-size supraalveolar peri-implant defect model in dogs. J Periodontol 2010;81:1839-1849.
  21. Becker J, Kirsch A, Schwarz F, Chatzinikolaidou M, Rothamel D, Lekovic V, et al. Bone apposition to titanium implants biocoated with recombinant human bone morphogenetic protein-2 (rhBMP-2). A pilot study in dogs. Clin Oral Investig 2006;10:217-224.
  22. Jones AA, Buser D, Schenk R, Wozney J, Cochran DL. The effect of rhBMP-2 around endosseous implants with and without membranes in the canine model. J Periodontol 2006;77:1184-1193.
  23. Langer R, Vacanti JP. Tissue engineering. Science 1993; 260:920-926.
  24. Park JC, So SS, Jung IH, Yun JH, Choi SH, Cho KS, et al. Induction of bone formation by Escherichia coli-expressed recombinant human bone morphogenetic protein-2 using block-type macroporous biphasic calcium phosphate in orthotopic and ectopic rat models. J Periodontal Res 2011;46:682-690.
  25. Rohrer MD, Schubert CC. The cutting-grinding technique for histologic preparation of undecalcified bone and bone-anchored implants. Improvements in instrumentation and procedures. Oral Surg Oral Med Oral Pathol 1992;74: 73-78.
  26. Jeon O, Rhie JW, Kwon IK, Kim JH, Kim BS, Lee SH. In vivo bone formation following transplantation of human adipose-derived stromal cells that are not differentiated osteogenically. Tissue Eng Part A 2008;14:1285-1294.
  27. Lee YJ, Jung SW, Chae GJ, Cho KS, Kim CS. The effect of recombinant human bone morphogenetic protein-2/macroporous biphasic calcium phosphate block system on bone formation in rat calvarial defects. J Korean Acad Periodontol 2007;37(Suppl):397-407.
  28. Lee JH, Kim CS, Choi KH, Jung UW, Yun JH, Choi SH, et al. The induction of bone formation in rat calvarial defects and subcutaneous tissues by recombinant human BMP-2, produced in Escherichia coli. Biomaterials 2010;31:3512-3519.
  29. Bessho K, Konishi Y, Kaihara S, Fujimura K, Okubo Y, Iizuka T. Bone induction by Escherichia coli -derived recombinant human bone morphogenetic protein-2 compared with Chinese hamster ovary cell-derived recombinant human bone morphogenetic protein-2. Br J Oral Maxillofac Surg 2000;38:645-649.
  30. Haidar ZS, Hamdy RC, Tabrizian M. Delivery of recombinant bone morphogenetic proteins for bone regeneration and repair. Part A: current challenges in BMP delivery. Biotechnol Lett 2009;31:1817-1824.
  31. Seeherman H, Wozney JM. Delivery of bone morphogenetic proteins for orthopedic tissue regeneration. Cytokine Growth Factor Rev 2005;16:329-345.
  32. Kawakatsu N, Oda S, Kinoshita A, Kikuchi S, Tsuchioka H, Akizuki T, et al. Effect of rhBMP-2 with PLGA/gelatin sponge type (PGS) carrier on alveolar ridge augmentation in dogs. J Oral Rehabil 2008;35:647-655.
  33. Schliephake H, Weich HA, Dullin C, Gruber R, Frahse S. Mandibular bone repair by implantation of rhBMP-2 in a slow release carrier of polylactic acid: an experimental study in rats. Biomaterials 2008;29:103-110.
  34. Le Nihouannen D, Saffarzadeh A, Gauthier O, Moreau F, Pilet P, Spaethe R, 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; 19:667-675.
  35. Le Nihouannen D, Guehennec LL, Rouillon T, Pilet P, Bilban M, Layrolle P, et al. Micro-architecture of calcium phosphate granules and fibrin glue composites for bone tissue engineering. Biomaterials 2006;27:2716-2722.
  36. Hong SJ, Kim CS, Han DK, Cho IH, Jung UW, Choi SH, et al. The effect of a fibrin-fibronectin/beta-tricalcium phosphate/recombinant human bone morphogenetic protein-2 system on bone formation in rat calvarial defects. Biomaterials 2006;27:3810-3816.
  37. Abarrategi A, Moreno-Vicente C, Ramos V, Aranaz I, Sanz Casado JV, Lopez-Lacomba JL. Improvement of porous beta-TCP scaffolds with rhBMP-2 chitosan carrier film for bone tissue application. Tissue Eng Part A 2008;14:1305-1319.
  38. Alam I, Asahina I, Ohmamiuda K, Enomoto S. Comparative study of biphasic calcium phosphate ceramics impregnated with rhBMP-2 as bone substitutes. J Biomed Mater Res 2001;54:129-138.
  39. Oda S, Kinoshita A, Higuchi T, Shizuya T, Ishikawa I. Ectopic bone formation by biphasic calcium phosphate (BCP) combined with recombinant human bone morphogenetic protein-2 (rhBMP-2). J Med Dent Sci 1997;44:53-62.

Cited by

  1. Clinical effect of hyperbaric oxygen therapy in the treatment of femoral head necrosis : A systematic review and meta-analysis vol.46, pp.5, 2012, https://doi.org/10.1007/s00132-016-3360-8
  2. Xenogeneic bone matrix immune risk assessment using GGTA1 knockout mice vol.46, pp.suppl3, 2012, https://doi.org/10.1080/21691401.2018.1493489
  3. Lateral onlay grafting using different combinations of soft‐type synthetic block grafts and resorbable collagen membranes: An experimental in vivo study vol.31, pp.4, 2012, https://doi.org/10.1111/clr.13566