The Use of Growth Factors for Guided Bone Regeneration in Clinical Periodontics

  • Harjit Singh SehgalEmail author
  • Steven D. Hokett
  • James A. Katancik
Clinical Periodontics (Y Stathopoulou, Section Editor)
Part of the following topical collections:
  1. Topical Collection on Clinical Periodontics


Purpose of Review

The primary purpose of this literature review is to determine the effectiveness of available growth factors for oral guided bone regeneration surgery in clinical periodontics. Secondarily, the authors clarify questions regarding the use of specific growth factors to optimize clinical outcomes.

Recent Findings

Current research indicates that growth factors may enhance initial periodontal wound healing; however, there is limited evidence to support their use in guided bone regeneration surgical procedures, to include peri-implant bone regeneration.


The use of biologic mediators, such as growth factors, as an adjunct to regeneration of extraction sites, edentulous site defects, or for dental implant site development must be carefully evaluated by clinicians to determine if the additional effort and expense will significantly enhance clinical outcome. Growth factors may provide the greatest benefit for enhanced wound healing in a compromised patient or in sites with severe hard and soft tissue defects or during retreatment.


Growth factor(s) Oral guided bone regeneration Dental implants 


Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.


Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. 1.
    Eskan MA, Greenwell H, Hill M, Morton D, Vidal R, Shumway B, et al. Platelet-rich plasma-assisted guided bone regeneration for ridge augmentation: a randomized, controlled clinical trial. J Periodontol. 2014;85(5):661–8. Scholar
  2. 2.
    Danesh-Meyer MJ, Filstein MR, Shanaman R. Histological evaluation of sinus augmentation using platelet rich plasma (PRP): a case series. J Int Acad Periodontol. 2001;3(2):48–56.PubMedGoogle Scholar
  3. 3.
    Torres J, Tamimi F, Martinez PP, Alkhraisat MH, Linares R, Hernandez G, et al. Effect of platelet-rich plasma on sinus lifting: a randomized-controlled clinical trial. J Clin Periodontol. 2009;36(8):677–87. Scholar
  4. 4.
    Huang L, Zou R, He J, Ouyang K, Piao Z. Comparing osteogenic effects between concentrated growth factors and the acellular dermal matrix. Braz Oral Res. 2018;32:e29. Scholar
  5. 5.
    Nevins ML, Camelo M, Schupbach P, Nevins M, Kim SW, Kim DM. Human buccal plate extraction socket regeneration with recombinant human platelet-derived growth factor BB or enamel matrix derivative. Int J Periodontics Restorative Dent. 2011;31(5):481–92.PubMedGoogle Scholar
  6. 6.
    Alkan EA, Parlar A, Yildirim B, Senguven B. Histological comparison of healing following tooth extraction with ridge preservation using enamel matrix derivatives versus Bio-Oss Collagen: a pilot study. Int J Oral Maxillofac Surg. 2013;42(12):1522–8. Scholar
  7. 7.
    Esberg A, Isehed C, Holmlund A, Lundberg P. Peri-implant crevicular fluid proteome before and after adjunctive enamel matrix derivative treatment of peri-implantitis. J Clin Periodontol. 2019;46(6):669–77. Scholar
  8. 8.
    Thoma DS, Payer M, Jakse N, Bienz SP, Hüsler J, Schmidlin PR. Randomized, controlled clinical two-centre study using xenogeneic block grafts loaded with recombinant human bone morphogenetic protein-2 or autogenous bone blocks for lateral ridge augmentation. J Clin Periodontol. 2018;45(2):265–76. Scholar
  9. 9.
    Huh JB, Lee HJ, Jang JW, Kim MJ, Yun PY, Kim SH, et al. Randomized clinical trial on the efficacy of Escherichia coli-derived rhBMP-2 with beta-TCP/HA in extraction socket. J Adv Prosthodont. 2011;3(3):161–5. Scholar
  10. 10.
    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(7):1281–90. Scholar
  11. 11.
    Coomes AM, Mealey BL, Huynh-Ba G, Barboza-Arguello C, Moore WS, Cochran DL. Buccal bone formation after flapless extraction: a randomized, controlled clinical trial comparing recombinant human bone morphogenetic protein 2/absorbable collagen carrier and collagen sponge alone. J Periodontol. 2014;85(4):525–35. Scholar
  12. 12.
    Fiorellini JP, Howell TH, Cochran D, Malmquist J, Lilly LC, Spagnoli D, et al. Randomized study evaluating recombinant human bone morphogenetic protein-2 for extraction socket augmentation. J Periodontol. 2005;76(4):605–13. Scholar
  13. 13.
    •• de Freitas RM, Susin C, Spin-Neto R, Marcantonio C, Wikesjo UM, Pereira LA. Horizontal ridge augmentation of the atrophic anterior maxilla using rhBMP-2/ACS or autogenous bone grafts: a proof-of-concept randomized clinical trial. J Clin Periodontol. 2013;40(10):968–75. manuscript demonstrates the de-novo bone regenration with use of rhBMP-2/ACS and its effectiveness similar to autogenous bone graft for horizontal ridge augmentation. CrossRefPubMedGoogle Scholar
  14. 14.
    Jung RE, Glauser R, Scharer P, Hammerle CH, Sailer HF, Weber FE. Effect of rhBMP-2 on guided bone regeneration in humans. Clin Oral Implants Res. 2003;14(5):556–68.CrossRefGoogle Scholar
  15. 15.
    Boyne PJ, Lilly LC, Marx RE, Moy PK, Nevins M, Spagnoli DB, et al. De novo bone induction by recombinant human bone morphogenetic protein-2 (rhBMP-2) in maxillary sinus floor augmentation. J Oral Maxillofac Surg. 2005;63(12):1693–707. Scholar
  16. 16.
    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(9):1947–60. Scholar
  17. 17.
    Froum SJ, Wallace S, Cho SC, Khouly I, Rosenberg E, Corby P, et al. Radiographic comparison of different concentrations of recombinant human bone morphogenetic protein with allogenic bone compared with the use of 100% mineralized cancellous bone allograft in maxillary sinus grafting. Int J Periodontics Restorative Dent. 2014;34(5):611–20. Scholar
  18. 18.
    Kao DW, Kubota A, Nevins M, Fiorellini JP. The negative effect of combining rhBMP-2 and Bio-Oss on bone formation for maxillary sinus augmentation. Int J Periodontics Restorative Dent. 2012;32(1):61–7.PubMedGoogle Scholar
  19. 19.
    Nevins ML, Reynolds MA. Tissue engineering with recombinant human platelet-derived growth factor BB for implant site development. Compend Contin Educ Dent. 2011;32(2):18 20-7; quiz 8, 40.PubMedGoogle Scholar
  20. 20.
    Nevins ML, Reynolds MA, Camelo M, Schupbach P, Kim DM, Nevins M. Recombinant human platelet-derived growth factor BB for reconstruction of human large extraction site defects. Int J Periodontics Restorative Dent. 2014;34(2):156–63. Scholar
  21. 21.
    Nevins ML, Camelo M, Nevins M, Schupbach P, Friedland B, Camelo JM, et al. Minimally invasive alveolar ridge augmentation procedure (tunneling technique) using rhPDGF-BB in combination with three matrices: a case series. Int J Periodontics Restorative Dent. 2009;29(4):371–83.PubMedGoogle Scholar
  22. 22.
    Simion M, Rocchietta I, Dellavia C. Three-dimensional ridge augmentation with xenograft and recombinant human platelet-derived growth factor-BB in humans: report of two cases. Int J Periodontics Restorative Dent. 2007;27(2):109–15.PubMedGoogle Scholar
  23. 23.
    Koch FP, Becker J, Terheyden H, Capsius B, Wagner W. A prospective, randomized pilot study on the safety and efficacy of recombinant human growth and differentiation factor-5 coated onto beta-tricalcium phosphate for sinus lift augmentation. Clin Oral Implants Res. 2010;21(11):1301–8. Scholar
  24. 24.
    Stavropoulos A, Becker J, Capsius B, Acil Y, Wagner W, Terheyden H. Histological evaluation of maxillary sinus floor augmentation with recombinant human growth and differentiation factor-5-coated beta-tricalcium phosphate: results of a multicenter randomized clinical trial. J Clin Periodontol. 2011;38(10):966–74. Scholar
  25. 25.
    Subramanian G, Cohen HV, Quek SY. A model for the pathogenesis of bisphosphonate-associated osteonecrosis of the jaw and teriparatideʼs potential role in its resolution. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2011;112(6):744–53. Scholar
  26. 26.
    Narongroeknawin P, Danila MI, Humphreys LG Jr, Barasch A, Curtis JR. Bisphosphonate-associated osteonecrosis of the jaw, with healing after teriparatide: a review of the literature and a case report. Spec Care Dent. 2010;30(2):77–82. Scholar
  27. 27.
    Zushi Y, Takaoka K, Tamaoka J, Ueta M, Noguchi K, Kishimoto H. Treatment with teriparatide for advanced bisphosphonate-related osteonecrosis of the jaw around dental implants: a case report. Int J Implant Dent. 2017;3(1):11. Scholar
  28. 28.
    Kuchler U, Luvizuto ER, Tangl S, Watzek G, Gruber R. Short-term teriparatide delivery and osseointegration: a clinical feasibility study. J Dent Res. 2011;90(8):1001–6. Scholar
  29. 29.
    Hahn J, Rohrer MD, Tofe AJ. Clinical, radiographic, histologic, and histomorphometric comparison of PepGen P-15 particulate and PepGen P-15 flow in extraction sockets: a same-mouth case study. Implant Dent. 2003;12(2):170–4.CrossRefGoogle Scholar
  30. 30.
    Hahn J. 8-year onlay bone graft and ridge augmentation with PepGen P-15: a clinical and radiographic case study. Implant Dent. 2004;13(3):228–31.CrossRefGoogle Scholar
  31. 31.
    Degidi M, Scarano A, Iezzi G, Orsini G, Perrotti V, Strocchi R, et al. Maxillary sinus augmentation using a synthetic cell-binding peptide: a histologic and transmission electron microscopy case study in man. Implant Dent. 2005;14(4):371–5.CrossRefGoogle Scholar
  32. 32.
    Alssum L, Eubank TD, Roy S, Erdal BS, Yildiz VO, Tatakis DN, et al. Gingival perfusion tissue biomarkers during early healing of postextraction regenerative procedures: a prospective case series. J Periodontol. 2017;88(11):1163–72. Scholar
  33. 33.
    Chiang T, Roca AL, Rostkowski S, Drew HJ, Simon B. Reconstruction of the narrow ridge using combined ridge split and guided bone regeneration with rhPDGF-BB growth factor-enhanced allograft. Int J Periodontics Restorative Dent. 2014;34(1):123–30. Scholar
  34. 34.
    • Lee EA. Subperiosteal minimally invasive aesthetic ridge augmentation technique (SMART): a new standard for bone reconstruction of the jaws. Int J Periodontics Restorative Dent. 2017;37(2):164–73. manuscript presents effectiveness of a minimally invasive surgical approach with the use of growth factors for ridge augmentation. CrossRefGoogle Scholar
  35. 35.
    Farina R, Bressan E, Taut A, Cucchi A, Trombelli L. Plasma rich in growth factors had limited effect on early bone formation in extraction sockets. Clin Oral Implants Res. 2014;25(10):1189–91. Scholar
  36. 36.
    Dragonas P, Palin C, Khan S, Gajendrareddy PK, Weiner WD. Complications associated with the use of recombinant human bone morphogenic protein–2 in ridge augmentation: a case report. J Oral Implantol. 2017;43(5):351–9. Scholar
  37. 37.
    Santana RB, Santana CMM, Dibart S. Platelet-derived growth factor-mediated guided bone regeneration in immediate implant placement in molar sites with buccal bone defects. Int J Periodontics Restorative Dent. 2015;35(6):824–33. Scholar
  38. 38.
    • Froum SJ, Froum SH, Rosen PS. A regenerative approach to the successful treatment of peri-implantitis: a consecutive series of 170 implants in 100 patients with 2-to 10-year follow-up. Int J Periodontics Restorative Dent. 2015;35(6):856–63. manuscript presents successful management of peri-implantitis defects with the use of growth factors. CrossRefGoogle Scholar
  39. 39.
    Isler SC, Soysal F, Ceyhanlı T, Bakırarar B, Unsal B. Regenerative surgical treatment of peri-implantitis using either a collagen membrane or concentrated growth factor: A 12-month randomized clinical trial. Clin Implant Dent Relat Res. 2018;20(5):703–12. Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Harjit Singh Sehgal
    • 1
    Email author
  • Steven D. Hokett
    • 1
  • James A. Katancik
    • 1
  1. 1.Department of Periodontology, School of DentistryOregon Health & Science UniversityPortlandUSA

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