Journal of Periodontal and Implant Science

Korean Academy of Periodontology (대한치주과학회)
권호 표지
DOI QR코드

DOI QR Code

Comparative analysis of carrier systems for delivering bone morphogenetic proteins

  • Jung, Im-Hee (Department of Dental Hygiene, Eulji University College of Health Science) ;
  • Lim, Hyun-Chang (Department of Periodontology, Kyung Hee University School of Dentistry) ;
  • Lee, Eun-Ung (Department of Periodontology, Research Institute for Periodontal Regeneration, Yonsei University College of Dentistry) ;
  • Lee, Jung-Seok (Department of Periodontology, Research Institute for Periodontal Regeneration, Yonsei University College of Dentistry) ;
  • Jung, Ui-Won (Department of Periodontology, Research Institute for Periodontal Regeneration, Yonsei University College of Dentistry) ;
  • Choi, Seong-Ho (Department of Periodontology, Research Institute for Periodontal Regeneration, Yonsei University College of Dentistry)
  • Received : 2015.07.15
  • Accepted : 2015.08.15
  • Published : 2015.08.30
Download PDF
⟨ Previous Next ⟩

Abstract

Purpose: The objective of this study was to comparatively assess the bone regenerative capacity of absorbable collagen sponge (ACS), biphasic calcium phosphate block (BCP) and collagenated biphasic calcium phosphate (CBCP) loaded with a low dose of recombinant human bone morphogenetic protein-2 (rhBMP-2). Methods: The CBCP was characterized by X-ray diffraction and scanning electron microscopy. In rabbit calvaria, four circular 8-mm-diameter defects were created and assigned to one of four groups: (1) blood-filled group (control), (2) rhBMP-2-soaked absorbable collagen sponge (0.05 mg/mL, 0.1 mL; CS group), (3) rhBMP-2-loaded BCP (BCP group), or (4) rhBMP-2-loaded CBCP (CBCP group). The animals were sacrificed either 2 weeks or 8 weeks postoperatively. Histological and histomorphometric analyses were performed. Results: The CBCP showed web-like collagen fibrils on and between particles. Greater dimensional stability was observed in the BCP and CBCP groups than in the control and the CS groups at 2 and 8 weeks. The new bone formation was significantly greater in the BCP and CBCP groups than in the control and CS groups at 2 weeks, but did not significantly differ among the four groups at 8 week. The CBCP group exhibited more new bone formation in the intergranular space and in the center of the defect compared to the BCP group at 2 weeks, but a similar histologic appearance was observed in both groups at 8 weeks. Conclusions: The dose of rhBMP-2 in the present study enhanced bone regeneration in the early healing period when loaded on BCP and CBCP in rabbit calvarial defects.

Keywords

References

  1. 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;54:129-38. https://doi.org/10.1002/1097-4636(200101)54:1<129::AID-JBM16>3.0.CO;2-D
  2. Chang YY, Lee JS, Kim MS, Choi SH, Chai JK, Jung UW. Comparison of collagen membrane and bone substitute as a carrier for rhBMP-2 in lateral onlay graft. Clin Oral Implants Res 2015;26:e13-9. https://doi.org/10.1111/clr.12320
  3. Jung RE, Weber FE, Thoma DS, Ehrbar M, Cochran DL, Hammerle CH. Bone morphogenetic protein-2 enhances bone formation when delivered by a synthetic matrix containing hydroxyapatite/tricalciumphosphate. Clin Oral Implants Res 2008;19:188-95. https://doi.org/10.1111/j.1600-0501.2007.01431.x
  4. Kim JS, Cha JK, Cho AR, Kim MS, Lee JS, Hong JY, et al. Acceleration of Bone Regeneration by BMP-2-Loaded Collagenated Biphasic Calcium Phosphate in Rabbit Sinus. Clin Implant Dent Relat Res. Forthcoming 2014.
  5. Kim JW, Choi KH, Yun JH, Jung UW, Kim CS, Choi SH, et al. Bone formation of block and particulated biphasic calcium phosphate lyophilized with Escherichia coli-derived recombinant human bone morphogenetic protein 2 in rat calvarial defects. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2011;112:298-306. https://doi.org/10.1016/j.tripleo.2010.10.025
  6. Lopes NM, Vajgel A, de Oliveira DM, de Santana Santos T, Wassall T. Use of rhBMP-2 to reconstruct a severely atrophic mandible: a modified approach. Int J Oral Maxillofac Surg 2012;41:1566-70. https://doi.org/10.1016/j.ijom.2012.05.017
  7. Mehanna R, Koo S, Kim DM. Recombinant human bone morphogenetic protein 2 in lateral ridge augmentation. Int J Periodontics Restorative Dent 2013;33:97-102. https://doi.org/10.11607/prd.1347
  8. Kim YJ, Lee JY, Kim JE, Park JC, Shin SW, Cho KS. Ridge preservation using demineralized bone matrix gel with recombinant human bone morphogenetic protein-2 after tooth extraction: a randomized controlled clinical trial. J Oral Maxillofac Surg 2014; 72:1281-90. https://doi.org/10.1016/j.joms.2014.01.022
  9. Triplett RG, Nevins M, Marx RE, Spagnoli DB, Oates TW, Moy PK, et al. Pivotal, randomized, parallel evaluation of recombinant human bone morphogenetic protein-2/absorbable collagen sponge and autogenous bone graft for maxillary sinus floor augmentation. J Oral Maxillofac Surg 2009;67:1947-60. https://doi.org/10.1016/j.joms.2009.04.085
  10. Carragee EJ, Hurwitz EL, Weiner BK. A critical review of recombinant human bone morphogenetic protein-2 trials in spinal surgery: emerging safety concerns and lessons learned. Spine J 2011;11:471-91. https://doi.org/10.1016/j.spinee.2011.04.023
  11. Kim MS, Lee JS, Shin HK, Kim JS, Yun JH, Cho KS. Prospective randomized, controlled trial of sinus grafting using Escherichia-coli-produced rhBMP-2 with a biphasic calcium phosphate carrier compared to deproteinized bovine bone. Clin Oral Implants Res. Forthcoming 2014.
  12. Choi Y, Lee JS, Kim YJ, Kim MS, Choi SH, Cho KS, et al. Recombinant human bone morphogenetic protein-2 stimulates the osteogenic potential of the Schneiderian membrane: a histometric analysis in rabbits. Tissue Eng Part A 2013;19:1994-2004. https://doi.org/10.1089/ten.tea.2012.0724
  13. Leknes KN, Yang J, Qahash M, Polimeni G, Susin C, Wikesjo UM. Alveolar ridge augmentation using implants coated with recombinant human bone morphogenetic protein-2: radiographic observations. Clin Oral Implants Res 2008;19:1027-33. https://doi.org/10.1111/j.1600-0501.2008.01567.x
  14. Boerckel JD, Kolambkar YM, Dupont KM, Uhrig BA, Phelps EA, Stevens HY, et al. Effects of protein dose and delivery system on BMP-mediated bone regeneration. Biomaterials 2011;32:5241-51. https://doi.org/10.1016/j.biomaterials.2011.03.063
  15. Choi H, Park NJ, Jamiyandorj O, Hong MH, Oh S, Park YB, et al. Improvement of osteogenic potential of biphasic calcium phosphate bone substitute coated with synthetic cell binding peptide sequences. J Periodontal Implant Sci 2012;42:166-72. https://doi.org/10.5051/jpis.2012.42.5.166
  16. Kim JW, Jung IH, Lee KI, Jung UW, Kim CS, Choi SH, et al. Volumetric bone regenerative efficacy of biphasic calcium phosphate-collagen composite block loaded with rhBMP-2 in vertical bone augmentation model of a rabbit calvarium. J Biomed Mater Res A 2012;100:3304-13.
  17. Kim MS, Kwon JY, Lee JS, Song JS, Choi SH, Jung UW. Low-dose recombinant human bone morphogenetic protein-2 to enhance the osteogenic potential of the Schneiderian membrane in the early healing phase: in vitro and in vivo studies. J Oral Maxillofac Surg 2014;72:1480-94. https://doi.org/10.1016/j.joms.2014.03.027
  18. Choi Y, Yun JH, Kim CS, Choi SH, Chai JK, Jung UW. Sinus augmentation using absorbable collagen sponge loaded with Escherichia coli-expressed recombinant human bone morphogenetic protein 2 in a standardized rabbit sinus model: a radiographic and histologic analysis. Clin Oral Implants Res 2012;23:682-9. https://doi.org/10.1111/j.1600-0501.2011.02222.x
  19. Lu SX, Fiorini T, Lee J, Prasad HS, Buxton AN, Bisch FC, et al. Evaluation of a compression resistant matrix for recombinant human bone morphogenetic protein-2. J Clin Periodontol 2013;40:688-97. https://doi.org/10.1111/jcpe.12109
  20. McClellan JW, Mulconrey DS, Forbes RJ, Fullmer N. Vertebral bone resorption after transforaminal lumbar interbody fusion with bone morphogenetic protein (rhBMP-2). J Spinal Disord Tech 2006;19:483-6. https://doi.org/10.1097/01.bsd.0000211231.83716.4b
  21. Yun PY, Kim YK, Jeong KI, Park JC, Choi YJ. Influence of bone morphogenetic protein and proportion of hydroxyapatite on new bone formation in biphasic calcium phosphate graft: two pilot studies in animal bony defect model. J Craniomaxillofac Surg 2014;42:1909-17. https://doi.org/10.1016/j.jcms.2014.07.011
  22. Kim DM, Nevins ML, Lin Z, Fateh A, Kim SW, Schupbach P, et al. The clinical and histologic outcome of dental implant in large ridge defect regenerated with alloplast: a randomized controlled preclinical trial. J Oral Implantol 2013;39:148-53. https://doi.org/10.1563/AAID-JOI-D-12-00242
  23. Nevins M, Nevins ML, Schupbach P, Kim SW, Lin Z, Kim DM. A prospective, randomized controlled preclinical trial to evaluate different formulations of biphasic calcium phosphate in combination with a hydroxyapatite collagen membrane to reconstruct deficient alveolar ridges. J Oral Implantol 2013;39:133-9. https://doi.org/10.1563/AAID-JOI-D-12-00185
  24. 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;113:480-7. https://doi.org/10.1016/j.tripleo.2011.04.013
  25. Yang CR, Wang YJ, Chen XF, Zhao NR. Biomimetic fabrication of BCP/COL/HCA scaffolds for bone tissue engineering. Mater Lett 2005;59:3635-40. https://doi.org/10.1016/j.matlet.2005.07.022
  26. Brodie JC, Goldie E, Connel G, Merry J, Grant MH. Osteoblast interactions with calcium phosphate ceramics modified by coating with type I collagen. J Biomed Mater Res A 2005;73:409-21.
  27. Brodie JC, Merry J, Grant MH. The mechanical properties of calcium phospate ceramics modified by collagen coating and populated by osteoblasts. J Mater Sci Mater Med 2006;17:43-8.
  28. Hsu EL, Ghodasra JH, Ashtekar A, Nickoli MS, Lee SS, Stupp SI, et al. A comparative evaluation of factors influencing osteoinductivity among scaffolds designed for bone regeneration. Tissue Eng Part A 2013;19:1764-72. https://doi.org/10.1089/ten.tea.2012.0711
  29. Seeherman H, Wozney J, Li R. Bone morphogenetic protein delivery systems. Spine (Phila Pa 1976) 2002;27:S16-23. https://doi.org/10.1097/00007632-200208151-00005
  30. LeGeros RZ, Lin S, Rohanizadeh R, Mijares D, LeGeros JP. Biphasic calcium phosphate bioceramics: preparation, properties and applications. J Mater Sci Mater Med 2003;14:201-9. https://doi.org/10.1023/A:1022872421333
  31. Yang C, Unursaikhan O, Lee JS, Jung UW, Kim CS, Choi SH. Osteoconductivity and biodegradation of synthetic bone substitutes with different tricalcium phosphate contents in rabbits. J Biomed Mater Res B Appl Biomater 2014;102:80-8. https://doi.org/10.1002/jbm.b.32984
  32. Mate-Sanchez de Val JE, Mazon P, Guirado JL, Ruiz RA, Ramirez Fernandez MP, Negri B, et al. Comparison of three hydroxyapatite/beta-tricalcium phosphate/collagen ceramic scaffolds: an in vivo study. J Biomed Mater Res A 2014;102:1037-46. https://doi.org/10.1002/jbm.a.34785
  33. Hwang JW, Park JS, Lee JS, Jung UW, Kim CS, Cho KS, et al. Comparative evaluation of three calcium phosphate synthetic block bone graft materials for bone regeneration in rabbit calvaria. J Biomed Mater Res B Appl Biomater 2012;100:2044-52.
  34. Wikesjo UM, Huang YH, Polimeni G, Qahash M. Bone morphogenetic proteins: a realistic alternative to bone grafting for alveolar reconstruction. Oral Maxillofac Surg Clin North Am 2007;19:535-51, vi-vii. https://doi.org/10.1016/j.coms.2007.07.004
  35. Montesano R, Orci L, Vassalli P. In vitro rapid organization of endothelial cells into capillary-like networks is promoted by collagen matrices. J Cell Biol 1983;97:1648-52. https://doi.org/10.1083/jcb.97.5.1648
  36. Raines EW. The extracellular matrix can regulate vascular cell migration, proliferation, and survival: relationships to vascular disease. Int J Exp Pathol 2000;81:173-82.

Cited by

  1. rhBMP-2 in an injectable Gelfoam carrier enhances consolidation of the distracted callus in a sheep model vol.25, pp.6, 2017, https://doi.org/10.3233/thc-170944
  2. Sinus augmentation using rhBMP-2-loaded synthetic bone substitute with simultaneous implant placement in rabbits vol.47, pp.2, 2015, https://doi.org/10.5051/jpis.2017.47.2.86
  3. Escherichia coli BMP-2 showed comparable osteoinductivity with Chinese hamster ovary derived BMP-2 with demineralized bone matrix as carrier vol.37, pp.1, 2015, https://doi.org/10.1080/08977194.2019.1596905
  4. The Effect of Autogenous Bone Graft Mixed With Recombinant Human Vascular Endothelial Growth Factor on Bone Regeneration vol.32, pp.6, 2015, https://doi.org/10.1097/scs.0000000000007316
  5. Improved bone regeneration using collagen-coated biphasic calcium phosphate with high porosity in a rabbit calvarial model vol.16, pp.1, 2015, https://doi.org/10.1088/1748-605x/abb1fc