Journal of Periodontal and Implant Science

Korean Academy of Periodontology (대한치주과학회)
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rhBMP-2 using biphasic calcium phosphate block as a carrier induces new bone formation in a rat subcutaneous tissue

  • Kim, Joon-Il (Department of Periodontology, Research Institute for Periodontal Regeneration, College of Dentistry, Yonsei University) ;
  • Yun, Jeong-Ho (Department of Dentistry, College of Medicine, Kwandong University, Myongji Hospital) ;
  • Chae, Gyung-Joon (Department of Periodontology, Research Institute for Periodontal Regeneration, College of Dentistry, Yonsei University) ;
  • Jung, Sung-Won (Department of Periodontology, Research Institute for Periodontal Regeneration, College of Dentistry, Yonsei University) ;
  • Kim, Chang-Sung (Department of Periodontology, Research Institute for Periodontal Regeneration, College of Dentistry, Yonsei University) ;
  • Cho, Kyoo-Sung (Department of Periodontology, Research Institute for Periodontal Regeneration, College of Dentistry, Yonsei University)
  • Published : 2008.08.15
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Abstract

Purpose: The carrier for the delivery of bone morphogenetic proteins(BMPs) should also serve as a scaffold for new bone growth. In addition, predictable bone formation in terms of the volume and shape should be guaranteed. This study evaluated the ectopic bone formation of recombinant human BMP-2(rhBMP-2) using a micro macroporous biphasic calcium phosphate (MBCP: mixture of ${\beta}TCP$ and HA) block as a carrier in a rat subcutaneous assay model. Materials and Methods: Subcutaneous pockets were created on the back of 40 male Sprague-Dawley rats. In the pockets, rhBMP-2/MBCP and MBCP alone were implanted. The blocks were evaluated by histological and histometric parameters after a healing interval of 2 weeks (each 10 rats; MBCP and rhBMP-2/MBCP) or 8 weeks (each 10 rats; MBCP and rhBMP-2/MBCP). Results: The shape and volume of the block was maintained stable over the healing period. No histological bone forming activity was observed in the MBCP alone sites after 2 weeks and there was minimal new bone formation at 8 weeks. In the rhBMP-2/MBCP sites, new bone formation was evident in the macropores of the block. The new bone area at 8 weeks was greater than at 2 weeks. There was a further increase in the quantity of new bone with the more advanced stage of remodeling. Conclusions: A MBCP block could serve as a carrier system for predictable bone tissue engineering using rhBMPs.

Keywords

References

  1. Urist MR. Bone: Formation by autoinduction. Science 1965;150:893-899. https://doi.org/10.1126/science.150.3698.893
  2. Ahn SH, Kim CS, Suk HJ, et al. Effect of recombinant human bone morphogenetic protein- 4 with carriers in rat calvarial defects. J Periodontol 2003;74:787-797. https://doi.org/10.1902/jop.2003.74.6.787
  3. Pang EK, Im SU, Kim CS, et al. Effect of recombinant human bone morphogenetic protein-4 dose on bone formation in rat calvarial defect model. J Periodontol 2004;75:1364-1370. https://doi.org/10.1902/jop.2004.75.10.1364
  4. Aldinger G, Herr G, Kusswetter W, et al. Bone morphogenetic protein: a review. Int Orthop 1991;15:169-177.
  5. Sampath TK, Maliakal JC, Hauschka PV. Recombinant human osteogenic protein-1 (hOP-1) induces new bone formation in vivo with a specific activity comparable with natural bovine osteogenic protein and stimulates osteoblast proliferation and differentiation in vitro. J Biol Chem 1992;267:20352-20362.
  6. Han DK, Kim CS, Jung UW, et al. Effect of a fibrin-fibronectin sealing system as a carrier for recombinant human bone morphogenetic protein-4 on bone formation in rat calvarial defects. J Periodontol 2005;76:2216-2222. https://doi.org/10.1902/jop.2005.76.12.2216
  7. Jung UW, Choi SY, Pang EK, et al. The Effect of varying the particle size of beta tricalcium phosphate carrier of recombinant human bone morphogenetic protein-4 on bone formation in rat calvarial defects. J Periodontol 2006;77: 765-772. https://doi.org/10.1902/jop.2006.050268
  8. Yasko AW, Lane JM, Fellinger EJ, et al. The healing of segmental bone defects, induced by recombinant human bone morphogenetic protein (rhBMP-2). A radiographic, histological, and biomechanical study in rats. J Bone Joint Surg Am 1992;74:659-670. https://doi.org/10.2106/00004623-199274050-00005
  9. Kim CS, Choi SH, Choi BK, et al. The effect of recombinant human bone morphogenetic protein-4 on the osteoblastic differentiation of mouse calvarial cells affected by Porphyromonas gingivalis. J Periodontol 2002;73:1126-1132. https://doi.org/10.1902/jop.2002.73.10.1126
  10. Hyun SJ, Choi SH, Chai JK, et al. Effect of recombinant human bone morphogenetic protein-2, -4 and -7 on bone formation in rat calvarial defects. J Periodontol 2005;76: 1667-1674. https://doi.org/10.1902/jop.2005.76.10.1667
  11. Choi SH, Kim CK, Cho KS, et al. Effect of recombinant human bone morphogenetic protein-2/absorbable collagen sponge (rhBMP-2/ACS) on healing in 3-wall intrabony defects in dogs. J Periodontol 2002;73:63-72. https://doi.org/10.1902/jop.2002.73.1.63
  12. Lindholm TS, Gao TJ. Functional carriers for bone morphogenetic proteins. Ann Chir Gynaecol Suppl 1993;207:3-12.
  13. Kim CS, Kim JI, Kim J, et al. Ectopic bone formation associated with recombinant human bone morphogenetic protein-2 using absorbable collagen sponge and beta tricalcium phosphate as carriers. Biomaterials 2005;26:2501-2507. https://doi.org/10.1016/j.biomaterials.2004.07.015
  14. Kawamura M, Urist MR. Human fibrin is a physiologic delivery system for bone morphogenetic protein. Clin Orthop Relat Res 1988;235:302-310.
  15. Hong SJ, Kim CS, Han DK, et al. The effect of a fibrin-fibronectin/ß-tricalcium phosphate/recombinant human bone morphogenetic protein-2 system on bone formation in rat calvarial defects. Biomaterials 2006;27:3810-3816. https://doi.org/10.1016/j.biomaterials.2006.02.045
  16. Gao TJ, Kousinioris NA, Wozney JM, Winn S, Uludag H. Synthetic thermoreversible polymers are compatible with osteoinductive activity of recombinant human bone morphogenetic protein 2. Tissue Eng 2002;8:429-440. https://doi.org/10.1089/107632702760184691
  17. Miki T, Imai Y. Osteoinductive potential of freeze-derived, biodegredable, poly(glycolic acid-co-lactic acid) disks incorporated with bone morphogenetic protein in skull defects of rats. Int J Oral Maxillofac Surg 1996;25:402-426. https://doi.org/10.1016/S0901-5027(06)80042-1
  18. Nery EB, LeGeros RZ, Lynch KL, Lee K. Tissue response to biphasic calcium phosphate ceramic with different ratios of HA/beta TCP in periodontal osseous defects. J Periodontol 1992 ;63:729-735. https://doi.org/10.1902/jop.1992.63.9.729
  19. LeGeros RZ, Lin S, Rohanizadeh R, Mijares D, LeGeros JP. Biphasic calcium phosphate bioceramics: preparation, properties and applications. J Master Sci Mater Med 2003;14:201-209. https://doi.org/10.1023/A:1022872421333
  20. Cornell CN, Lane JM. Current understanding of osteoconduction in bone regeneration. Clin Orthop Relat Res 1998;355 Suppl:S267-273.
  21. Schopper C, Ziya-Ghazvini F, Goriwoda W, et al. HA/TCP compounding of a porous CaP biomaterial improves bone formation and scaffold degradation--a long-term histological study. J Biomed Mater Res B Appl Biomater 2005;74:458-467.
  22. Manjubala I, Sastry TP, Kumar RV. Bone in-growth induced by biphasic calcium phosphate ceramic in femoral defect of dogs. J Biomater Appl 2005;19:341-360. https://doi.org/10.1177/0885328205048633
  23. Gauthier O, Bouler JM, Aguado E, Pilet P, Daculsi G. Macroporous biphasic calcium phosphate ceramics: influence of macropore diameter and macroporosity percentage on bone ingrowth. Biomaterials 1998;19:133-139. https://doi.org/10.1016/S0142-9612(97)00180-4
  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. https://doi.org/10.1023/A:1022842404495
  25. Habibovic P, Yuan H, van den Doel M, et al. Relevance of osteoinductive biomaterials in critical-sized orthotopic defect. J Orthop Res 2006;24:867-876. https://doi.org/10.1002/jor.20115
  26. Le Nihouannen D, Daculsi G, Saffarzadeh A, et al. Ectopic bone formation by microporous calcium phosphate ceramic particles in sheep muscles. Bone 2005;36:1086-1093. https://doi.org/10.1016/j.bone.2005.02.017
  27. Yuan H, van Blitterswijk CA, de Groot K, de Bruijn JD. A comparison of bone formation in biphasic calcium phosphate (BCP) and hydroxyapatite (HA) implanted in muscle and bone of dogs at different time periods. J Biomed Mater Res A 2006;78:139-147.
  28. Le Guehennec L, Goyenvalle E, Aguado E, et al. Small-animal models for testing macroporous ceramic bone substitutes. J Biomed Mater Res B Appl Biomater 2005;72: 69-78.
  29. 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.
  30. Boden SD, Kang J, Sandhu H, Heller JG. Use of recombinant human bone morphogentic protein-2 to achieve posterolateral lumbar spine fusion in humans: a prospective, randomized clinical pilot trial: 2002 Volvo Award in clinical studies. Spine 2002;27:2662-2273. https://doi.org/10.1097/00007632-200212010-00005
  31. Okubo Y, Bessho K, Fujimura K, et al. Comparative study of intramuscular and intraskeletal osteogenesis by recombinant human bone morphogenetic protein-2. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1999;87:34-8. https://doi.org/10.1016/S1079-2104(99)70291-X
  32. Yoshida K, Bessho K, Fujimura K, et al. Osteoinduction capability of recombinant human bone morphogenetic protein-2 in intramuscular and subcutaneous sites: an experimental study. J Craniomaxillofac Surg 1998;26:112-115. https://doi.org/10.1016/S1010-5182(98)80050-4
  33. Daculsi G, Layrolle P. Osteoinductive properties of micro macroporous biphasic calcium phosphate bioceramics. Key Eng Mater 2004;254-256:1005-1008. https://doi.org/10.4028/www.scientific.net/KEM.254-256.1005
  34. Yang Z, Yuan H, Tong W, et al. Osteogenesis in extraskeletally implanted porous calcium phosphate ceramics: variability among different kinds of animals. Biomaterials 1996;17:2131-2137. https://doi.org/10.1016/0142-9612(96)00044-0