EFFECT OF RHPDGF-BB AND RHBMP-2 ON OSSEOINTEGRATION OF TITANIUM IMPLANTS AT PERIIMPLANT BONE DEFECTS GRAFTED WITH HYDROXYAPATITE: MICRO-CT AND HISTOLOGIC ANALYSIS

Hydroxyapatite를 이식한 임플란트 주위 골결손부에서 rhPDGF-BB와 rhBMP-2가 골내 임플란트 osseointegration에 미치는 영향: Micro-CT 분석과 조직학적 평가

  • Park, Jee-Hyun (Department of Oral and Maxillofacial Surgery, College of Dentistry, Seoul National University) ;
  • Hwang, Sun-Jung (Department of Oral and Maxillofacial Surgery, College of Dentistry, Seoul National University) ;
  • Kim, Myung-Jin (Department of Oral and Maxillofacial Surgery, College of Dentistry, Seoul National University)
  • 박지현 (서울대학교 치과대학 구강악안면외과학교실) ;
  • 황순정 (서울대학교 치과대학 구강악안면외과학교실) ;
  • 김명진 (서울대학교 치과대학 구강악안면외과학교실)
  • Received : 2009.10.27
  • Accepted : 2009.11.13
  • Published : 2009.11.20

Abstract

Purpose: Platelet derived growth factor(PDGF)-BB and bone morphogenetic protein(BMP)-2 are well-known representative growth factors. The purposes of this study were to investigate the effect of rhPDGFBB and rhBMP-2 on osseointegration of titanium implants at periimplant bone defects grafted with hydroxyapatite and to evaluate the feasibility of imaging bone structures around screw-type titanium implant with micro-CT. Materials and Methods: The first molar and all premolars in the mandible region of four beagle dogs were extracted. Following a healing period of 4 months, three $8{\times}8{\times}6mm$-sized bony defects were formed and screw-type titanium implants were placed with hydroxyapatite(HA) block and growth factors; Control group, PDGF group and BMP group. Two months post-implantation, the mandible was harvested. Bone volume(BV), bone-to-implant contact(BIC) and bone mineral density(BMD) were analyzed with micro-CT and histology. Results: According to micro-CT analysis, BV and BMD measures of PDGF and BMP group were significantly higher than control group(BV; PDGF group: $p{\fallingdotseq}0.011$, BMP group: $p{\fallingdotseq}0.006$/BMD; PDGF group: $p{\fallingdotseq}0.020$, BMP group: $p{\fallingdotseq}0.011$) and BIC measures of BMP group were significantly higher than PDGF group($p{\fallingdotseq}0.015$). In histologic evaluation, BIC measures of BMP group was significantly higher than PDGF group($p{\fallingdotseq}0.048$). The values of BV in histologic sections were higher than in micro-CT images and the values of BIC in micro-CT images were higher than in histologic sections. Conclusion: The findings of this experimental study indicates that the use of rhPDGF-BB and rhBMP-2 can increase new bone formation in a large bony defect around titanium implant, and rhBMP-2 is more effective than rhPDGF-BB. Micro-CT can be considered useful for assessment as a rapid and nondestructive method for 3-dimensional measurement of bone healing around implants. Further study is necessary, however, to remove metal artifacts around titanium implant and to standardize the method.

Keywords

References

  1. Buser D, Dula K, Hess D et al : Localized ridge augmentation with autografts and barrier membranes. Periodontology 19 : 151, 1999 https://doi.org/10.1111/j.1600-0757.1999.tb00153.x
  2. Laurie SWS, Kaban LB, Mulliken JB et al : Donor site morbidity after harvesting rib and iliac bone. Plastic and Reconstructive Surgery 73 : 933, 1984 https://doi.org/10.1097/00006534-198406000-00014
  3. Sommers BN, Eisenstein SM : Donor site pain from the ileum : a complication of lumbar spine fusion. Journal of Bone and Joint Surgery 71 : 677, 1984
  4. Younger EM, Chapman MW : Morbidity at bone graft donor sites. Journal of Orthopedics Trauma 3 : 192, 1989 https://doi.org/10.1097/00005131-198909000-00002
  5. Friedlaender GE, Horowitz MC : Immune responses to osteochondral allografts: nature and significance. Orthopedics 15(10) : 1171, 1992
  6. Carlson ER, Marx RE, Buck BE : The potential for HIV transmission through allogeneic bone. A review of risks and safety. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 80(1) : 17, 1995 https://doi.org/10.1016/S1079-2104(95)80010-7
  7. Langer R, Vacanti JP : Tissue engineering. Science 260 : 920, 1993 https://doi.org/10.1126/science.8493529
  8. Yamada Y, Ueda M, Naiki T et al : Tissue-engineered injectable bone regeneration for osseointegrated dental implants. Clin Oral Implants Res Oct ; 15(5) : 589, 2004 https://doi.org/10.1111/j.1600-0501.2004.01038.x
  9. Ito K, Yamada Y, Naiki T et al : Simultaneous implant placement and bone regeneration around dental implants using tissue-engineered bone with fibrin glue, mesenchymal stem cells and platelet-rich plasma. Clin Oral Implants Res 17(5) : 579, 2006 https://doi.org/10.1111/j.1600-0501.2006.01246.x
  10. Vacanti JP, Langer R : Tissue engineering; the design and fabrication of living replacement devices for surgical reconstruction and transplantation. Lancet 354(Suppl.1) : S132, 1999 https://doi.org/10.1016/S0140-6736(99)90247-7
  11. Bucholz RW, Carlton A, Holmes RE : Hydroxyapatite and tricalcium phosphate bone graft substitute. Orthop Clin North Am 18 : 323, 1987
  12. Radin SR, Ducheyne P : Effect of bioactive ceramic composition and structure on in vitro behavior, III: porous versus dense ceramics. J Biomed Mater Res 28 : 1303, 1994 https://doi.org/10.1002/jbm.820281108
  13. Redey SA, Razzouk S, Rey C et al : Osteoclast adhesion and activity on synthetic hydroxyapatite, carbonated hydroxyapatite, and natural calcium carbonate : relationship to surface energies. J Biomed Mater Res 45 : 140, 1999 https://doi.org/10.1002/(SICI)1097-4636(199905)45:2<140::AID-JBM9>3.0.CO;2-I
  14. Horner A, Bord S, Kemp P et al : Distribution of plateletderived growth factor(PDGF) A chain mRNA, protein and PDGF-alpha receptor in rapidly forming human bone. Bone 19 : 353, 1996 https://doi.org/10.1016/S8756-3282(96)00217-7
  15. Urist MR : Bone Formation by autoinduction. Science 150 : 893, 1965 https://doi.org/10.1126/science.150.3698.893
  16. Urist MR, DeLange RJ, Finerman GAM : Bone cell differentiation and growth factors, Science 220 : 680, 1983 https://doi.org/10.1126/science.6403986
  17. Urist MR, Huo YK, Brownell AG et al : Purification of bovine bone morphogenetic protein by hydroxy apatite chromatography. proc Natl Acad Sci USA 81 : 371, 1984 https://doi.org/10.1073/pnas.81.2.371
  18. Yasko AW, Cole BJ, Lane JM et al : The healing of segmental bone defects induced by rhBMP-2. J Bone Joint Surg Am 74A : 659, 1992
  19. Miamoto S, Takaoka K, Yoshikawa H et al : Trans-filter bone induction in monkeys by BMP. Trans ORS 99, 1993
  20. Sigurdsson TJ, Fu E, Tatakis DN et al : Bone morphogenetic protein-2 for peri-implant bone regeneration and osseointegration. Clin Oral Implants Res 8 : 367, 1997 https://doi.org/10.1034/j.1600-0501.1997.080503.x
  21. Jovanovic SA, Hunt DR, Bernard GW et al : Longtermfunctional loading of dental implants in rhBMP-2 inducedbone. A histologic study in the canine ridge augmentation model. Clin Oral Implants Res 14 : 793, 2003 https://doi.org/10.1046/j.0905-7161.2003.clr140617.x
  22. Sorensen RG, Wikesjo UM, Kinoshita A et al : Periodontal repair in dogs: Evaluation of a bioresorbable calcium phosphate cement (Ceredex) as a carrier for rhBMP-2. J Clin Periodontol 31 : 796, 2004 https://doi.org/10.1111/j.1600-051X.2004.00544.x
  23. Cochran DL, Nummikoski PV, Jones AA et al : Radiographic analysis of regenerated bone around endosseous implants in the canine using recombinant human bonemorphogenetic protein-2. Int J Oral Maxillofac Implants 12 : 739, 1997
  24. Cochran DL, Schenk R, Buser D et al : Recombinant human bone morphogenetic protein-2 stimulation of bone formation around endosseous dental implants. J Periodontol 70 : 139, 1999 https://doi.org/10.1902/jop.1999.70.2.139
  25. Donath K, Breuner G : A method for the study of undecalcified bones and teeth with attached soft tissues. J Oral Pathol 11 : 318, 1982 https://doi.org/10.1111/j.1600-0714.1982.tb00172.x
  26. Feldkamp LA, Goldstein SA, Parfitt AM et al : The direct examination of three-dimensional bone architectures in vitro by computed tomography. J Bone Miner Res 4 : 3, 1989 https://doi.org/10.1002/jbmr.5650040103
  27. Kapadia RD, Stroup GB, Badger AM et al : Applications of micro-CT and MR microscopy to study pre-clinical models of osteoporosis and osteoarthritis. Technol Health Care 6 : 361, 1998
  28. Verna C, Bosch G, Dalstra M et al : Healing patterns in calvarial bone defects following guided bone regeneration in rats. A micro-CT scan analysis. J Clin Periodontol 29 : 865, 2002 https://doi.org/10.1034/j.1600-051X.2002.290912.x
  29. Patel V, Issever AS, Burghardt A et al : Micro-CT evaluation of normal and osteoarthritic bone structure in human knee specimens. J Orthop Res 21 : 6, 2003 https://doi.org/10.1016/S0736-0266(02)00093-1
  30. Balto K, Muller R, Garrington DC et al : Quantification of periapical bone destruction in mice by micro-computed tomography. J Dent Res 79 : 35, 2000 https://doi.org/10.1177/00220345000790010401
  31. Giesen EB, van Eijden TM : The three-dimensional cancellous bone architecture of the human mandibular condyle. J Dent Res 79 ; 957, 2000 https://doi.org/10.1177/00220345000790041101
  32. Van Oosterwyck H, Vander Sloten J, Van der Perre G et al : The use of microfocus computerized tomography (micro-CT) as a new technique to characterize bone tissue around oral implants. J Oral Implantol 26 : 5, 2000 https://doi.org/10.1563/1548-1336(2000)026<0005:TUOMCT>2.3.CO;2
  33. Sennerby L, Wennerberg A, Pasop F : A new microtomographic technique for non-invasive evaluation of the bone structure around implants. Clin Oral Implants Res 12 : 91, 2001 https://doi.org/10.1034/j.1600-0501.2001.012001091.x
  34. Bergmans L, Van Cleynenbreugel J, Wevers M et al : A methodology for quantitative evaluation of root canal instrumentation using microcomputed tomography. Int Endod J 34 : 390, 2001 https://doi.org/10.1046/j.1365-2591.2001.00413.x
  35. Jones AA, Buser D, Schenk R et al : The effect of rhBMP-2 around endosseous implants with and without membranes in the canine model. J Periodontol 77(7) : 1184, 2006 https://doi.org/10.1902/jop.2006.050337
  36. Meraw SJ, Reeve CM, Lohse CM et al : Treatment of peri-implant defects with comfbination growth factor cement. J Periodontol 71(1) : 8, 2000 https://doi.org/10.1902/jop.2000.71.1.8
  37. Rocchietta I, Dellavia C, Nevins M et al : Bone regenerated via rhPDGF-BB and a deproteinized bovine bone matrix: back scattered electron microscopic element analysis. Int J Period Restr Dent 27(6) : 539, 2007
  38. Simion M, Rocchietta I, Kim D et al : Vertical ridge augmentation by means of deproteinized bovine blone block and recombinant human platelet-derived growth factor-BB: a histologic study in a dog model. Int J Period Restr Dent 26 : 415, 2006
  39. Tsiridis E, Bhalla A, Ali Z et al : Enhancing the osteoinductive properties of hydroxyapatite by the addition of human osteogenic protein-1(BMP-7) in vitro. Injury, Int J. Care injured 37S : S25, 2006 https://doi.org/10.1016/j.injury.2006.08.021
  40. Yoshikawa H, Akira M : Bone tissue engineering with porous hydroxyapatite ceramics. J Artif Organs 8 : 131, 2005 https://doi.org/10.1007/s10047-005-0292-1
  41. Mosekilde L : Consequences of the remodelling process for vertebral trabecular bone structure; A scanning electron microscopy study (uncoupling of unloaded structures). Bone miner 10 : 13, 1990 https://doi.org/10.1016/0169-6009(90)90046-I
  42. Odgaard A, Andersen K, Melsen F et al : A direct method for fast three-dimensional serial reconstruction. J Microsc 159 : 335, 1990 https://doi.org/10.1111/j.1365-2818.1990.tb03038.x
  43. Butz F, Ogawa T, Chang TL et al : Int J Oral Maxillofac Implants. 21(5) : 687, 2006
  44. Suetens P : Fundamentals of medical imaging. Cambridge, UK : Cambridge University Press p.85, 2002
  45. Stoppie N, Van Der Waerden JP, Jansen JA et al : Validation of microfocus computed tomography in the evaluation of bone implant specimens. Clin Implant Dent Relat Res 7:87, 2005 https://doi.org/10.1111/j.1708-8208.2005.tb00051.x
  46. Rebaudi A, Koller B, Laib A et al : Microcomputed tomographic analysis of the peri-implant bone. Int J Periodontics Restorative Dent 24 : 316, 2004
  47. Stoppie N, Wevers M, Naert I : Feasibility of detecting trabecular bone around percutaneous titanium implants in rabbits by in vivo microfocus computed tomography. J Microsc 228(Pt1) : 55, 2007 https://doi.org/10.1111/j.1365-2818.2007.01823.x
  48. Ruegsegger P, Koller B, Muller R : A microtomographic system for the nondestructive evaluation of bone architecture. Calcif Tissue Int 58 : 24, 1996 https://doi.org/10.1007/BF02509542