Biomaterials Research (생체재료학회지)

Korean Society for Biomaterials (한국생체재료학회)
권호 표지
DOI QR코드

DOI QR Code

Rapid bone regeneration by Escherichia coli-derived recombinant human bone morphogenetic protein-2 loaded on a hydroxyapatite carrier in the rabbit calvarial defect model

  • Chung, Chung-Hoon (Department of Periodontology, College of Dentistry, Yonsei University) ;
  • Kim, You-Kyoung (Department of Periodontology, College of Dentistry, Yonsei University) ;
  • Lee, Jung-Seok (Department of Periodontology, College of Dentistry, Yonsei University) ;
  • Jung, Ui-Won (Department of Periodontology, College of Dentistry, Yonsei University) ;
  • Pang, Eun-Kyoung (Department of Periodontology, School of Medicine, Ewha Womans University) ;
  • Choi, Seong-Ho (Department of Periodontology, College of Dentistry, Yonsei University)
  • Received : 2015.04.22
  • Accepted : 2015.06.19
  • Published : 2015.09.30
⟨ Previous Next ⟩

Abstract

Background: The aim of this study was to determine the osteoconductivity of hydroxyapatite particles (HAP) as a carrier for Escherichia coli-derived recombinant human bone morphogenetic protein-2 (ErhBMP-2). Two 8-mm diameter bicortical calvarial defects were created in each of 20 rabbits. One of each pair of defects was randomly assigned to be filled with HAP only (HAP group) or ErhBMP-2 loaded HAP (ErhBMP-2/HAP group), while the other defect was left untreated (control group). The animals were killed after either 2 weeks (n = 10) or 8 weeks (n = 10) of healing, and histological, histomorphometric, and tomographic analyses were performed. Results: All experimental sites showed uneventful healing during the postoperative healing period. In both histomorphometric and tomographic analyses, the new bone area or volume of the ErhBMP-2/HAP group was significantly greater than that of the HAP and control groups at 2 weeks (p < 0.05). However, at 8 weeks, no significant difference in new bone area or volume was observed between the ErhBMP-2/HAP and HAP groups. The total augmented area or volume was not significantly different between the ErhBMP-2/HAP and HAP groups at 2 and 8 weeks. Conclusions: Combining ErhBMP-2 with HAP could significantly promote rapid initial new bone formation. Moreover, HAP graft could increase new bone formation and space maintenance, therefore it might be one of the effective carriers of ErhBMP-2.

Keywords

Acknowledgement

Supported by : Yonsei University College

References

  1. Ebara S, Nakayama K. Mechanism for the action of bone morphogenetic proteins and regulation of their activity. Spine. 2002;27:S10-5. https://doi.org/10.1097/00007632-200208151-00004
  2. Hogan BL. Bone morphogenetic proteins: multifunctional regulators of vertebrate development. Genes Dev. 1996;10:1580-94. https://doi.org/10.1101/gad.10.13.1580
  3. Wozney JM. Overview of bone morphogenetic proteins. Spine. 2002;27:S2-8. https://doi.org/10.1097/00007632-200208151-00002
  4. Herford AS, Boyne PJ. Reconstruction of mandibular continuity defects with bone morphogenetic protein-2 (rhBMP-2). J Oral Maxillofac Surg. 2008;66:616-24. https://doi.org/10.1016/j.joms.2007.11.021
  5. Lan J, Wang ZF, Shi B, Xia HB, Cheng XR. The influence of recombinant human BMP-2 on bone-implant osseointegration: biomechanical testing and histomorphometric analysis. Int J Oral Maxillofac Surg. 2007;36:345-9. https://doi.org/10.1016/j.ijom.2006.10.019
  6. Ono M, Sonoyama W, Yamamoto K, Oida Y, Akiyama K, Shinkawa S, et al. Efficient bone formation in a swine socket lift model using Escherichia coli-derived recombinant human bone morphogenetic protein-2 adsorbed in beta-tricalcium phosphate. Cells Tissues Organs. 2014;199:249-55. https://doi.org/10.1159/000369061
  7. 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;38:645-9. https://doi.org/10.1054/bjom.2000.0533
  8. 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
  9. Lee JK, Cho LR, Um HS, Chang BS, Cho KS. Bone formation and remodeling of three different dental implant surfaces with Escherichia coli-derived recombinant human bone morphogenetic protein 2 in a rabbit model. Int J Oral Maxillofac Implants. 2013;28:424-30. https://doi.org/10.11607/jomi.2751
  10. 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;27:3810-6. https://doi.org/10.1016/j.biomaterials.2006.02.045
  11. Hannink G, Arts JJ. Bioresorbability, porosity and mechanical strength of bone substitutes: what is optimal for bone regeneration? Injury. 2011;42 Suppl 2:S22-5.
  12. Annis P, Brodke DS, Spiker WR, Daubs MD, Lawrence BD. The fate of L5-S1 with low dose BMP-2 and pelvic fixation, with or without interbody fusion, in adult deformity surgery. Spine. 2015. doi:10.1097/BRS.0000000000000867.
  13. Yoshida K, Bessho K, Fujimura K, Konishi Y, Kusumoto K, Ogawa Y, et al. Enhancement by recombinant human bone morphogenetic protein-2 of bone formation by means of porous hydroxyapatite in mandibular bone defects. J Dent Res. 1999;78:1505-10. https://doi.org/10.1177/00220345990780090401
  14. Jensen SS, Broggini N, Hjorting-Hansen E, Schenk R, Buser D. Bone healing and graft resorption of autograft, anorganic bovine bone and betatricalcium 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
  15. Guda T, Darr A, Silliman DT, Magno MH, Wenke JC, Kohn J, et al. Methods to analyze bone regenerative response to different rhBMP-2 doses in rabbit craniofacial defects. Tissue Eng Part C Methods. 2014;20:749-60. https://doi.org/10.1089/ten.tec.2013.0581
  16. Jiang ZQ, Liu HY, Zhang LP, Wu ZQ, Shang DZ. Repair of calvarial defects in rabbits with platelet-rich plasma as the scaffold for carrying bone marrow stromal cells. Oral Surg Oral Med Oral Pathol Oral Radiol. 2012;113:327-33. https://doi.org/10.1016/j.tripleo.2011.03.026
  17. Schmidlin PR, Nicholls F, Kruse A, Zwahlen RA, Weber FE. Evaluation of moldable, in situ hardening calcium phosphate bone graft substitutes. Clin Oral Implants Res. 2013;24:149-57. https://doi.org/10.1111/j.1600-0501.2011.02315.x
  18. 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. https://doi.org/10.1016/j.tripleo.2010.05.011
  19. Visser R, Arrabal PM, Becerra J, Rinas U, Cifuentes M. The effect of an rhBMP- 2 absorbable collagen sponge-targeted system on bone formation in vivo. Biomaterials. 2009;30:2032-7. https://doi.org/10.1016/j.biomaterials.2008.12.046
  20. 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
  21. Liu WC, Robu IS, Patel R, Leu MC, Velez M, Chu TM. The effects of 3D bioactive glass scaffolds and BMP-2 on bone formation in rat femoral critical size defects and adjacent bones. Biomed Mater. 2014;9:045013. https://doi.org/10.1088/1748-6041/9/4/045013
  22. Ong JL, Bess EG, Bessho K. Osteoblast progenitor cell responses to characterized titanium surfaces in the presence of bone morphogenetic protein-atelopeptide type I collagen in vitro. J Oral Implantol. 1999;25:95-100. https://doi.org/10.1563/1548-1336(1999)025<0095:OPCRTC>2.3.CO;2
  23. Bessho K, Carnes DL, Cavin R, Chen HY, Ong JL. BMP stimulation of bone response adjacent to titanium implants in vivo. COIR. 1999;10:212-8.
  24. Zhu W, Wang D, Zhang X, Lu W, Han Y, Ou Y, et al.Experimental study of nano-hydroxyapatite/recombinant human bone morphogenetic protein-2 composite artificial bone. Artif Cells Blood Substit Immobil Biotechnol. 2010;38:150-6. https://doi.org/10.3109/10731191003712756
  25. Turhani D, Weissenbock M, Stein E, Wanschitz F, Ewers R. Exogenous recombinant human BMP-2 has little initial effects on human osteoblastic cells cultured on collagen type I coated/noncoated hydroxyapatite ceramic granules. J Oral Maxillofac Surg. 2007;65:485-93. https://doi.org/10.1016/j.joms.2005.12.065
  26. Lee KB, Taghavi CE, Song KJ, Sintuu C, Yoo JH, Keorochana G, et al. Inflammatory characteristics of rhBMP-2 in vitro and in an in vivo rodent model. Spine. 2011;36:E149-54. https://doi.org/10.1097/BRS.0b013e3181f2d1ec
  27. Deutsch H. High-dose bone morphogenetic protein-induced ectopic abdomen bone growth. Spine J. 2010;10:e1-4.
  28. Tannoury CA, An HS. Complications with the use of bone morphogenetic protein 2 (BMP-2) in spine surgery. Spine J. 2014;14:552-9. https://doi.org/10.1016/j.spinee.2013.08.060
  29. Lee JW, Lim HC, Lee EU, Park JY, Lee JS, Lee DW, et al. Paracrine effect of the bone morphogenetic protein-2 at the experimental site on healing of the adjacent control site: a study in the rabbit calvarial defect model. J Periodontal Implant Sci. 2014;44:178-83. https://doi.org/10.5051/jpis.2014.44.4.178
  30. Crouzier T, Sailhan F, Becquart P, Guillot R, Logeart-Avramoglou D, Picart C. The performance of BMP-2 loaded TCP/HAP porous ceramics with a polyelectrolyte multilayer film coating. Biomaterials. 2011;32:7543-54. https://doi.org/10.1016/j.biomaterials.2011.06.062
  31. Patel ZS, Ueda H, Yamamoto M, Tabata Y, Mikos AG. In vitro and in vivo release of vascular endothelial growth factor from gelatin microparticles and biodegradable composite scaffolds. Pharm Res. 2008;25:2370-8. https://doi.org/10.1007/s11095-008-9685-1
  32. Hernandez A, Sanchez E, Soriano I, Reyes R, Delgado A, Evora C. Materialrelated effects of BMP-2 delivery systems on bone regeneration. Acta Biomater. 2012;8:781-91. https://doi.org/10.1016/j.actbio.2011.10.008
  33. Zhao J, Wang S, Bao J, Sun X, Zhang X, Zhang X, et al. Trehalose maintains bioactivity and promotes sustained release of BMP-2 from lyophilized CDHA scaffolds for enhanced osteogenesis in vitro and in vivo. PLoS One. 2013;8, e54645. https://doi.org/10.1371/journal.pone.0054645
  34. Lu Z, Huangfu C, Wang Y, Ge H, Yao Y, Zou P, et al. Kinetics and thermodynamics studies on the BMP-2 adsorption onto hydroxyapatite surface with different multi-morphological features. Mater Sci Eng C Mater Biol Appl. 2015;52:251-8. Submit https://doi.org/10.1016/j.msec.2015.03.047

Cited by

  1. miR‐33a‐5p modulates TNF‐α‐inhibited osteogenic differentiation by targeting SATB2 expression in hBMSCs vol.590, pp.3, 2016, https://doi.org/10.1002/1873-3468.12064
  2. A Fusion between Domains of the Human Bone Morphogenetic Protein-2 and Maize 27 kD γ-Zein Accumulates to High Levels in the Endoplasmic Reticulum without Forming Protein Bodies in Transgenic Tob vol.7, pp.None, 2016, https://doi.org/10.3389/fpls.2016.00358
  3. In Vitro and In Vivo Evaluation of Commercially Available Fibrin Gel as a Carrier of Alendronate for Bone Tissue Engineering vol.2017, pp.None, 2015, https://doi.org/10.1155/2017/6434169
  4. Radiographic and histologic effects of bone morphogenetic protein-2/hydroxyapatite within bioabsorbable magnesium screws in a rabbit model vol.14, pp.None, 2015, https://doi.org/10.1186/s13018-019-1143-8
  5. Dose Effects of Slow-Released Bone Morphogenetic Protein-2 Functionalized β-Tricalcium Phosphate in Repairing Critical-Sized Bone Defects vol.26, pp.3, 2015, https://doi.org/10.1089/ten.tea.2019.0161
  6. Comparison of demineralized bone matrix and hydroxyapatite as carriers of Escherichia coli recombinant human BMP-2 vol.25, pp.1, 2021, https://doi.org/10.1186/s40824-021-00225-7