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:: Volume 24, Issue 3 (7-2012) ::
J Islam Dent Assoc Iran 2012, 24(3): 122-138 Back to browse issues page
Effects of Different Growth Factors on New Bone Formation: A Systematic Review
Hosain Behnia1, Arash Khojasteh *2, Mohammad Esmaeelinejad3, Navid Naghdi4
1- Professor and Chairman , Department of Oral and Maxillofacial Surgery , School of Dentistry , Shahid Beheshti University of Medical Sciences . Tehran, Iran
2- Assistant Professor, Department of Oral and Maxillofacial Surgery , School of Dentistry , Shahid Beheshti University of Medical Sciences And Head of the Division of Basic Sciences, Dental Research Center . Tehran, Iran , arashkhojasteh@gmail.com
3- Resident of Oral and Maxillofacial Surgery Shahid Beheshti University of Medical Sciences . Tehran, Iran .
4- Resident of Oral and Maxillofacial Surgery , Isfehan University of Medical Sciences . Isfehan, Iran
Abstract:   (8640 Views)

  Background and Aim: Using different osteogenic growth factors, which is still under investigation, is a favorable method for bone regeneration. This systematic review is aimed at evaluating the effects of different growth factors and their carriers on osteogenesis .

  Materials and Methods: Electronic databases (Medline, EMBase and Cochrane) were studied by the authors for articles published from 1999 to October 2010. Clinical and animal studies evaluating bone formation by applying a specific growth factor and the related carrier were included in this investigation. Obtained data were organized in a table and evaluated through a qualitative analysis .

  Results: Sixty-nine studies most of which evaluated the effects of BMP-2 osteogenesis in different models were included in this study. Totally, twenty-five carriers were applied with different growth factors in the experiments. Among these carriers, poly lactic– co glycolic acid (PLGA), hydroxy apatite/tricalcium phosphate/absorbable collagen sponge (HA/TCP/ACS) and BioOss were the most frequently used carriers with the growth factors in bone regeneration studies.

  Conclusion: The current evidence, although not strong enough, confirms that BMP-2 has more favorable results in osteogenesis compared with other factors. The carrier scaffold, methods of measurement (histologic or radiographic), type of animal, defect diameter and the length of follow-up are the variables that should be matched before reaching definite results for the effect of growth factors in bone regeneration .


Keywords: Growth factors, Bone regeneration, New bone formation, Carrier, BMP
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Type of Study: Orginal | Subject: Oral and Maxillofacial
1. Haidar ZS, Hamdy RC, Tabrizian M. Delivery of recombinant bone morphogenetic proteins for bone regeneration and repair. Part A: Cur-rent challenges in BMP Delivery. Biotechnol Lett. 2009 Dec; 31(12):1817-24.
2. Weinstein SL. The Bone and Joint Decade.J Bone Joint Surg Am. 2000 Jan; 82(1):1-3.
3. Block MS, Kent JN. Sinus augmentation for dental implants: the use of autogenous bone. J Oral Maxillofac Surg. 1997 Nov; 55(11):1281-6.
4. Geiger M, Li RH, Friess W. Collagen sponges for bone regeneration with rh-BMP-2. Adv Drug Deliv Rev. 2003 Nov 28; 55(12):1613-29.
5. Bishop GB, Einhorn TA. Current and future clinical application of bone morphogenetic pro-teins in orthopedic trauma surgery. Int Orthop. 2007 Dec; 31(6):721-7.
6. Rose FR, Hou Q, Oreffo RO. Delivery sys-tems for bone growth factors- the new players in skeletal regenerations. J Pharm Pharmacol. 2004 Apr; 56(4):415-27.
7. Kimelman N, Palled G, Helm GA, Huard J, Schwarz EM, Gazit D. Review: Gene and stem cell-based therapeutics for bone regeneration and repair. Tissue Eng. 2007 Jun; 13(6):1135-50.
8. Moore YR, Dickinson DP, Wikesjo¨ UME. Growth/differentiation factor-5: A candidate therapeutic agent for periodontal regeneration? A review of pre-clinical data. J Clin Periodontol 2010 Nov; 37(3):288-298.
9. Bessa PC, Casal M, Reis RL. Bone morpho-genetic proteins in tissue engineering: the road from the laboratory to the clinic, part I (basic concepts). J Tissue Eng Regen Med. 2008 Jan; 2 (1):1-13.
10. Leach JK, Kaigler D, Wang Zh, Krebsbach PH, Mooney DJ. Coating of VEGF-releasing scaffolds with bioactive glass for angiogenesis and bone regeneration. Biomaterials. 2006 Jun; 27(17):3249-55.
11. De la Riva B, Sanchez E, Hernandez A, Reyes R, Tamimi F, López-Cabarcos E, et al. Local controlled release of VEGF and PDGF from a combined brushite-chitosan system en-hances bone regeneration. J Control Release. 2010 Apr 2; 143(1):45-52.
12. Yamamoto M, Tabata Y, Hang L, Miyamoto S, Hashimoto N, Ikeda Y. Bone regeneration by transforming growth factor B1 released from a biodegradable hydrogel. J Control Release. 2000 Feb 14; 64(1-3):133-42.
13. Vaccaro AR, Whang PG, Patel T, Phillips FM, Anderson DG, Albert TJ, et al. The safety and efficacy of OP-1 (rhBMP-7) as a replace-ment for iliac crest autograft for posterolateral lumbar arthrodesis: Minimum 4-year follow-up of a pilot study. Spine J. 2008 May-Jun; 8(3): 457-65.
14. Young S, Patel ZS, Kretlow JD, Murphy MB, Mountziaris PM, Baggett LS, et al. Dose effect of dual delivery of vascular endothelial growth factor and bone morphogenetic protein-2 on bone regeneration in a rat critical-size de-fect model. Tissue Eng Part A. 2009 Sep; 15(9): 2347-62.
15. Kanczler JM, Ginty PJ, White L, Clarke NM, Howdle SM, Shakesheff KM, et al. The effect of the delivery of vascular endothelial growth factor and bone bonemorphogenic protein-2 to osteoprogenitor cell populations on bone for-mation. Biomaterials 2010 Feb; 31(6):1242-50.
16. Maissen O, Eckhardt C, Gogolewski S, Glatt M, Arvinte T, Steiner A, et al. Mechanical and radiological assessment of the influence of rhTGFb-3 on bone regeneration in a segmental defect in the ovine tibia: Pilot Study. J Orthop Res. 2006 Aug; 24(8):1670-8.
17. Kokubo S, Fujimoto R, Yokota S, Fukushi-ma S, Nozaki K, Takahashi K, et al. Bone re-generation by recombinant human bone mor-phogenetic protein-2 and a novel biodegradable carrier in a rabbit ulnar defect model. Bio-materials 2003 Apr; 24(9):1643-51.
18. Marukawa E, Asahina I, Oda M, Seto I, Alam MI, Enomoto S. Bone regeneration using recombinant human bone morphogenetic pro-tein-2 (rhBMP-2) in alveolar defects of primate mandibles. Br J Oral Maxillofac Surg. 2001 Dec; 39(6):452-9.
19. Kempen DH, Lu L, Heijink A, Hefferan TE, Creemers LB, Maran A, et al. Effect of local sequential VEGF and BMP-2 delivery on ectop-ic and orthotopicbone regeneration. Biomateri-als 2009 May; 30(14):2816-25.
20. Matin K, Senpuku H, Hanada N, Ozawa H, Ejiri S. Bone regeneration by recombinant hu-man bone morphogenetic protein-2 around im-mediate implants: A Pilot Study in Rats. Int J Oral Maxillofac Implants. 2003 Mar-Apr; 18(2): 211-7.
21. Aghaloo T, Cowan CM, Zhang X, Freymiller E, Soo C, Wu B, et al. The Effect of NELL1 and Bone Morphogenetic Protein-2 on Calvarial Bone Regeneration.J Oral Maxillofac Surg. 2010 Feb; 68(2):300-8.
22. Arosarena O, Collins W. Bone regeneration in the rat mandible with bone morphogenetic protein-2: A comparison of two carriers. Oto-laryngol Head Neck Surg. 2005 Apr; 132(4):592-7.
23. Miranda DA, Blumenthal NM, Sorensen RG, Wozney JM, Wikesjo UM. Evaluation of re-combinant human bone morphogenetic protein-2 on the repair of alveolar ridge defects in ba-boons. J Periodontol. 2005 Feb; 76(2):210-20.
24. Carstens MH, Chin M, Li J. In Situ Osteo-genesis: Regeneration of 10-cm mandibular de-fect in porcine model using recombinant human bone morphogenetic protein-2 (rhBMP-2) and helistat absorbable collagen sponge. J Craniofac Surg. 2005 Nov; 16(6):1033-42.
25. Jovanovic SA, Hunt DR, Bernard GW, Spiekermann H, Wozney JM, Wikesjo UM. Bone reconstruction following implantation of rhBMP-2 and guided bone regeneration in ca-nine alveolar ridge defects. Clin Oral Implants Res. 2007 Apr; 18(2):224-30.
26. Wikesjö UM, Qahash M, Thomson RC, Cook AD, Rohrer MD, Wozney JM, et al. rhBMP-2 significantly enhances guided bone regeneration. Clin Oral Implants Res. 2004 Apr; 15(2):194-204.
27. Jung RE, Glauser R, Scharer P, Hammerle CHF, Sailer HF, Weber FE. Effect of rhBMP-2 on guided bone regeneration in humans. Clin Oral Implants Res. 2003 Oct; 14(5):556-68.
28. Cochran DL, Jones AA, Lilly LC, Fiorellini JP, Howell H. Evaluation of recombinant hu-man bone morphogenic protein-2 in oral appli-cation icludin use of endosseous implants: 3-year results of a pilot study in humans. J Perio-dontol. 2000 Aug; 71(8):1241-57.
29. Takahashi Y, Yamamoto M, Yamada K, Kawakami O, Tabata Y. Skull bone regenera-tion in nonhuman primates by controlled release of bone morphogenetic protein-2 from a biode-gradable hydrogel. Tissue Eng. 2007 Feb;13(2): 293-300.
30. Yamamoto M, Takahashi Y, Tabata Y. En-hanced bone regeneration at a segmental bone defect by controlled release of bone morphoge-netic protein-2 from a biodegradable hydrogel. Tissue Eng. 2006 May; 12(5):1305-11.
31. Arosarena O, Collins W. Comparison of BMP-2 and -4 for rat mandibular bone regen-eration at various doses. OrthodCraniofac Res. 2005 Nov; 8(4):267-76.
32. Kim J, Kim IS, Cho TH, Lee KB, Hwang SJ, Tae G, et al. Bone regeneration using hyaluronic acid-based hydrogel with bone morphogenic protein-2 and human mesenchymal stem cells. Biomaterials. 2007 Apr; 28(10):1830-7.
33. Chu TG, Warden SH, Turner CH, Stewart RL. Segmental bone regeneration using a load-bearing biodegradable carrier of bone morpho-genetic protein-2. Biomaterials 2007 Jan; 28(3): 459-67.
34. Allegrini S, Yoshimoto M, Salles MB, Konig B. Bone regeneration in rabbit sinus lifting as-sociated with bovine BMP. J Biomed Mater Res B Appl Biomater. 2004 Feb 15; 68(2):127-31.
35. Kleinheinz J, Stratmann U, Joos U, Wies-mann HP. VEGF-Activated Angiogenesis during Bone Regeneration. J Oral Maxillofac Surg. 2005 Sep; 63(9):1310-6.
36. Samee M, Kasugai S, Kondo H, Ohya K, ShimokawaH, Kuroda S. Bone morphogenetic protein-2 (BMP-2) and vascular endothelial growth factor (VEGF) transfection to human periosteal cells enhances osteoblast differentia-tion and bone formation. J Pharmacol Sci. 2008 Sep; 108(1):18-31.
37. Hokugo A, Sawada Y, Hokugo R, Iwamura H, Kobuchi M, Kambara T, et al. Controlled release of platelet growth factors enhances bone regeneration at rabbit calvaria. Oral Surg Oral Med Oral Pathol Oral RadiolEndod. 2007 Jul; 104(1):44-48.
38. Fuerst G, Gruber R, Tangl S, Mittlböck M, Sanroman F, Watzek G, et al. Effect of platelet-released growth factors and collagen type I on osseous regeneration of mandibular defects. J Clin Periodontol.2004 Sep; 31(9):784-790.
39. Ehrhart NP, Hong L, Morgan AL, Eurell JA, Jamison RD. Effect of transforming growth fac-tor-β1 on bone regeneration in critical-sized bone defects after irradiation of host tissues. Am J Vet Res. 2005 Jun;66(6):1039-1045.
40. Marzouk KM, Gamal AY, Al-Awady AA, Sharawy MM. Platelet-derived growth factor BB treated osteoprogenitorsinhibit bone regenera-tion. J Oral Implantol. 2008; 34(5):242-247.
41. Sawada Y, Hokugo A, Nishiura A, Hokugo R, Matsumoto N, Morita S, et al. A trial of alve-olar cleft bone regeneration by controlled re-lease of bone morphogenetic protein: an exper-imental study in rabbits. Oral Surg Oral Med Oral Pathol Oral RadiolEndod.2009 Dec; 108(6):812-820.
42. Patel ZS, Young S, Tabata Y, Jansen JA, Wong ME, Mikos AG, et al. Dual delivery of an angiogenic and an osteogenic growth factor for bone regeneration in a critical size defect mod-el. J Bone. 2008 Nov; 43(5):931-940.
43. Canter HI, Vargel I, Korkusuz P, Oner F, Gungorduk DB, Cil B, et al. Effect of use of slow release of bone morphogenetic protein-2 and transforming growth factor-beta-2 in a chi-tosan gel matrix on cranial bone graft survival in experimental cranial critical size defect mod-el. Ann Plast Surg. 2010 Mar;64(3):342-350.
44. Chung Y, Ahn KM, Jeon SH, Lee SY, Lee JH, Tae G. Enhanced bone regeneration with BMP-2 loaded functional nanoparticle–hydrogel complex. J Control Release.2007 Aug; 121(1-2): 91-99.
45. Kaitoa T, Myouia A, Takaoka K, Saito N, Nishikawa M, Tamai N, et al. Potentiation of the activity of bone morphogenetic protein-2 in bone regeneration by a PLA–PEG/hydroxyapatite composite. J Biomaterials. 2005 Jan; 26(1):73-79.
46. Asamura S, Mochizuki Y, Yamamoto M, Tabata Y, Isogai N.Bone regeneration using a bone morphogenetic protein-2 saturated slow-release gelatin hydrogel sheet, evaluation in a canine orbital floor fracture model. Ann Plast Surg.2010 Apr; 64(4):496-502.
47. 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 Oct; 108(4):e3-e12.
48. Tatakis DN, Koh A, Jin L, Wozney JM, Rohrer MD, Wikesjö UM.Peri-implant bone re-generation using recombinant human bone morphogenetic protein-2 in a canine model:a dose-response study. J Periodont Res.2002 Apr; 37 (2):93-100.
49. Sykaras N, Triplett RG, Nunn ME, Iacopino AM, Opperman LA. Effect of recombinant hu-man bone morphogenetic protein-2 on bone regeneration and osseointegration of dental im-plants. Clin Oral Implants Res. 2001 Aug; 12(4): 339-349.
50. Jung RE, Windisch SI, Eggenschwiler AM, Thoma DS, Weber FE, Hämmerle CHF. A ran-domized-controlled clinical trial evaluating clin-ical and radiological outcomes after 3 and 5 years of dental implants placed in bone regen-erated by means of GBR techniques with or without the addition of BMP-2. Clin Oral Im-plants Res. 2009 Jul; 20(7):660-666.
51. Chen B, Lin H, Wang J, Zhao Y, Wang B, Zhao W, et al. Homogeneous osteogenesis and bone regeneration by demineralized bone ma-trix loading with collagen-targeting bone mor-phogenetic protein-2. Biomaterials 2007 Feb; 28(6): 1027-1035.
52. Schwarz F, Ferrari D, Podolsky L, Mihatovic I, Becker J. Initial pattern of angiogenesis and bone formation following lateral ridge augmen-tation using rhPDGF and guided bone regenera-tion: an immunohistochemical study in dogs. Clin Oral Implants Res.2010 Jan; 21(1):90-99.
53. Nevins M, Camelo M, Nevins ML, Schenk RK, Lynch SE. Periodontal regeneration in hu-mans using recombinant human platelet derived growth factor-BB (rhPDGF-BB) andallogenic bone. J Periodontol. 2003 Sep; 74(9):1282-1292.
54. Schwarz F, Sager M, Ferrari D, Mihatovic I, Becker JR. Influence of recombinant human platelet-derived growth factor on lateral ridge augmentation using biphasic calcium phosphate and guided bone regeneration: A histomorpho-metric study in dogs. J Periodontol. 2009 Aug; 80(8):1315-1323.
55. Yonamine Y, Matsuyama T, Sonomura T, Takeuchi H, Furuichi Y, Uemura M, et al. Ef-fectable application of vascular endothelial growth factor to critical sized rat calvaria de-fects. Oral Surg Oral Med Oral Pathol Oral Ra-diol Endod; 2010 Feb; 109(2):225-231.
56. Wernike E, Montjovent M, Liu Y, Wismeijer D, Hunziker EB, Siebenrock KA, et al. VEGF incorporated into calcium phosphate ceramics promotesvascularisation and bone formation INVIVO. Eur Cell Mater. 2010 Feb; 19:30-40.
57. Niedhart C, Maus U, Miltner O, Gräber HG, Niethard FU, Siebert CH. The effect of basic fibroblast growth factor on bone regeneration when released from a novel in situ setting trical-cium phosphate cement. J Biomed Mater Res A. 2004 Jun 15; 69(4):680-685.
58. Akagawa Y, Kubo T, Koretake K, Hayashi K, Doi K, Matsuura A, et al. Initial bone regen-eration around fenestrated implants in Beagle dogs using basic fibroblast growth factor–gelatin hydrogel complex with varying biodeg-radation rates. J Prosthodont Res. 2009 Jan; 53(1):41-47.
59. Yuan Q, Kubo T, Doi K, Morita K, Takeshita R, Katoh S, et al. Effect of combined application of bFGF and inorganic polyphos-phate on bioactivities of osteoblasts and initial bone regeneration. Ac-ta Biomater. 2009 Jun; 5(5):1716-1724.
60. Murakami S, Takayama S, Kitamura M, Shimabukuro Y, Yanagi K, Ikezawa K, et al. Recombinant human basic fibroblast growth factor (bFGF) stimulates periodontal regenera-tion in class II furcation defects created in bea-gle dogs. J Periodontal Res. 2003 Feb; 38(1):97-103.
61. Ichinohe N, Kuboki Y, Tabata K. Bone re-generation using titanium nonwoven fabrics combined with fgf-2 release from gelatin hy-drogel microspheres in rabbit skull defects. Tis-sue Eng Part A. 2008 Oct; 14(10):1663-1671.
62. Kitamura M, Nakashima K, Kowashi Y, Fu-jii T, Shimauchi H, Sasano T, et al. Periodontal tissue regeneration using fibroblast growth fac-tor -2: randomized controlled phase II clinical trial. PLoS One. 2008 Jul 2; 3(7):e2611.
63. Ripamonti U, Parak R, Petit J-C.Induction ofcementogenesis and periodontal ligament re-generation by recombinant human transforming growth factor-b3in Matrigel with rectus abdom-inis responding cells. J Periodontal Res. 2009 Feb; 44(1):81-87.
64. Gruber RM, Ludwig A, Merten HA, Achilles M, Poehling S, Schliephake H. Sinus floor aug-mentation with recombinant human growth and differentiation factor-5 (rhGDF-5): A histologi-cal and histomorphometric study in the Goettin-gen miniature pig. Clin Oral Implants Res. 2008 May; 19(5):522-529
65. Weng D, Poehling S, Pippig S, Bell M, Rich-ter EJ, Zuhr O, et al. The effects of recombinant human growth/ differentiation factor-5(rhGDF-5) on bone regeneration around titanium dental implants in barrier membrane-protected defects: A pilot study in the mandible of beagle dogs. Int J Oral Maxillofac Implants. 2009 Jan-Feb; 24 (1):31-37.
66. Kim T-G, WikesjoUME, Cho K-S, Chai JK, Pippig SD, Siedler M, et al. Periodontal wound healing/ regeneration following implantation of recombinant human growth/ differentiation fac-tor-5 (rhGDF-5) in an absorbable collagen sponge carrier into one-wall intrabony defects indogs: adose-range study. J Clin Periodontol. 2009 Jul; 36 (7):589-597.
67. Schwarz F, Ferrari D, Sager M, Herten M, Hartig B, Becker J. Guided bone regeneration using rhGDF-5- and rhBMP-2 coated natural bone mineral in rat calvarial defects. Clin Oral Implants Res. 2009 Nov; 20(11):1219-1230.
68. Kikuchi T, Kubota S, Asaumi K, Kawaki H, Nishida T, Kawata K, et al. Promotion of bone regeneration by CCN2 incorporated into gelatin hydrogel. Tissue Eng Part A. 2008 Jun; 14(6): 1089-1098.
69. Christgau M, Moder D, Hiller KA, Dada A, Schmitz G, Schmalz G.Growth factors and cy-tokines in autologous platelet concentrate and their correlation to periodontal regeneration out-comes. J Clin Periodontol. 2006 Nov; 33(11): 837-845.
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Behnia H, Khojasteh A, Esmaeelinejad M, Naghdi N. Effects of Different Growth Factors on New Bone Formation: A Systematic Review. J Islam Dent Assoc Iran. 2012; 24 (3) :122-138
URL: http://jidai.ir/article-1-1253-en.html

Volume 24, Issue 3 (7-2012) Back to browse issues page
Journal of Islamic Dental Association of Iran


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