Growth Factors for Site Preparation: Current Science, Indications, and Practice

  • Tara AghalooEmail author
  • Rachel Lim


Implant restoration of the dentition poses many challenges in cases of limited bony foundation. Many patients suffer from loss of teeth and supporting bony structures through mechanisms including trauma, congenital abnormalities, or resorption secondary to tooth loss. In addition to classic alveolar ridge augmentation techniques and materials, growth factors are being studied to improve patient outcomes, especially in cases of larger, more challenging defects, in previously failed graft sites, and in stringent aesthetic cases. In this chapter, we will discuss three growth factors which are most commonly studied and US Food and Drug Administration approved: bone morphogenetic protein-2 (BMP-2), platelet-derived growth factor (PDGF), and platelet-rich protein/platelet-rich fibrin (PRP/PRF). Currently, growth factors are utilized in a wide variety of clinical situations, including guided bone regeneration, peri-implant defects, sinus augmentation, and socket augmentation. Furthermore, we will explore the future of growth factor usage, with new factors in various stages of investigation, combinations of materials, and viable cell therapy. Though much work has been done in the last few decades to reveal the clinical relevance of growth factors, much more research, both basic and clinical, must be performed to improve current technologies, develop predictable protocols, and evaluate long-term results.


Implants Surgery Growth factors Aesthetic zone Augmentation Grafting 


  1. 1.
    Suarez-Lopez Del Amo F, et al. Biologic agents for periodontal regeneration and implant site development. Biomed Res Int. 2015;2015:957518.PubMedPubMedCentralCrossRefGoogle Scholar
  2. 2.
    Higginbottom FL. Implants as an option in the esthetic zone. J Oral Maxillofac Surg. 2005;63(9 Suppl 2):33–44.PubMedCrossRefPubMedCentralGoogle Scholar
  3. 3.
    Aghaloo TL, Moy PK. Which hard tissue augmentation techniques are the most successful in furnishing bony support for implant placement? Int J Oral Maxillofac Implants. 2007;22(Suppl):49–70.PubMedPubMedCentralGoogle Scholar
  4. 4.
    Schliephake H. Clinical efficacy of growth factors to enhance tissue repair in oral and maxillofacial reconstruction: a systematic review. Clin Implant Dent Relat Res. 2015;17(2):247–73.PubMedCrossRefPubMedCentralGoogle Scholar
  5. 5.
    Miyazaki M, et al. An update on bone substitutes for spinal fusion. Eur Spine J. 2009;18(6):783–99.PubMedPubMedCentralCrossRefGoogle Scholar
  6. 6.
    Reddi AH. Morphogenesis and tissue engineering of bone and cartilage: inductive signals, stem cells, and biomimetic biomaterials. Tissue Eng. 2000;6(4):351–9.PubMedCrossRefPubMedCentralGoogle Scholar
  7. 7.
    Urist MR. Bone: formation by autoinduction. Science. 1965;150(3698):893–9.PubMedPubMedCentralCrossRefGoogle Scholar
  8. 8.
    Lavery K, et al. BMP-2/4 and BMP-6/7 differentially utilize cell surface receptors to induce osteoblastic differentiation of human bone marrow-derived mesenchymal stem cells. J Biol Chem. 2008;283(30):20948–58.PubMedPubMedCentralCrossRefGoogle Scholar
  9. 9.
    Poon B, et al. Bone morphogenetic protein-2 and bone therapy: successes and pitfalls. J Pharm Pharmacol. 2016;68(2):139–47.PubMedCrossRefPubMedCentralGoogle Scholar
  10. 10.
    Wozney JM. Overview of bone morphogenetic proteins. Spine (Phila Pa 1976). 2002;27(16 Suppl 1):S2–8.CrossRefGoogle Scholar
  11. 11.
    Yamaguchi A, Komori T, Suda T. Regulation of osteoblast differentiation mediated by bone morphogenetic proteins, hedgehogs, and Cbfa1. Endocr Rev. 2000;21(4):393–411.PubMedCrossRefPubMedCentralGoogle Scholar
  12. 12.
    Valdes MA, et al. Recombinant bone morphogenic protein-2 in orthopaedic surgery: a review. Arch Orthop Trauma Surg. 2009;129(12):1651–7.PubMedCrossRefPubMedCentralGoogle Scholar
  13. 13.
    Carreira AC, et al. Bone morphogenetic proteins: structure, biological function and therapeutic applications. Arch Biochem Biophys. 2014;561:64–73.PubMedCrossRefPubMedCentralGoogle Scholar
  14. 14.
    Boyne PJ, 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.PubMedCrossRefPubMedCentralGoogle Scholar
  15. 15.
    Triplett RG, 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.PubMedCrossRefPubMedCentralGoogle Scholar
  16. 16.
    Fiorellini JP, et al. Randomized study evaluating recombinant human bone morphogenetic protein-2 for extraction socket augmentation. J Periodontol. 2005;76(4):605–13.PubMedCrossRefGoogle Scholar
  17. 17.
    Carter TG, et al. Off-label use of recombinant human bone morphogenetic protein-2 (rhBMP-2) for reconstruction of mandibular bone defects in humans. J Oral Maxillofac Surg. 2008;66(7):1417–25.PubMedCrossRefPubMedCentralGoogle Scholar
  18. 18.
    Herford AS, Boyne PJ. Reconstruction of mandibular continuity defects with bone morphogenetic protein-2 (rhBMP-2). J Oral Maxillofac Surg. 2008;66(4):616–24.PubMedCrossRefPubMedCentralGoogle Scholar
  19. 19.
    Herford AS. rhBMP-2 as an option for reconstructing mandibular continuity defects. J Oral Maxillofac Surg. 2009;67(12):2679–84.PubMedCrossRefPubMedCentralGoogle Scholar
  20. 20.
    Fallucco MA, Carstens MH. Primary reconstruction of alveolar clefts using recombinant human bone morphogenic protein-2: clinical and radiographic outcomes. J Craniofac Surg. 2009;20(Suppl 2):1759–64.PubMedCrossRefPubMedCentralGoogle Scholar
  21. 21.
    Chin M, et al. Repair of alveolar clefts with recombinant human bone morphogenetic protein (rhBMP-2) in patients with clefts. J Craniofac Surg. 2005;16(5):778–89.PubMedCrossRefPubMedCentralGoogle Scholar
  22. 22.
    Herford AS, et al. Bone morphogenetic protein-induced repair of the premaxillary cleft. J Oral Maxillofac Surg. 2007;65(11):2136–41.PubMedCrossRefPubMedCentralGoogle Scholar
  23. 23.
    Canan LW Jr, et al. Human bone morphogenetic protein-2 use for maxillary reconstruction in cleft lip and palate patients. J Craniofac Surg. 2012;23(6):1627–33.PubMedCrossRefPubMedCentralGoogle Scholar
  24. 24.
    Cicciu M, et al. Recombinant human bone morphogenetic protein type 2 application for a possible treatment of bisphosphonates-related osteonecrosis of the jaw. J Craniofac Surg. 2012;23(3):784–8.PubMedCrossRefPubMedCentralGoogle Scholar
  25. 25.
    Alonso N, et al. Evaluation of maxillary alveolar reconstruction using a resorbable collagen sponge with recombinant human bone morphogenetic protein-2 in cleft lip and palate patients. Tissue Eng Part C Methods. 2010;16(5):1183–9.PubMedCrossRefPubMedCentralGoogle Scholar
  26. 26.
    Edmunds RK, et al. Maxillary anterior ridge augmentation with recombinant human bone morphogenetic protein 2. Int J Periodontics Restorative Dent. 2014;34(4):551–7.PubMedCrossRefPubMedCentralGoogle Scholar
  27. 27.
    Misch CM, et al. Vertical bone augmentation using recombinant bone morphogenetic protein, mineralized bone allograft, and titanium mesh: a retrospective cone beam computed tomography study. Int J Oral Maxillofac Implants. 2015;30(1):202–7.PubMedCrossRefPubMedCentralGoogle Scholar
  28. 28.
    Tarnow DP, et al. Maxillary sinus augmentation using recombinant bone morphogenetic protein-2/acellular collagen sponge in combination with a mineralized bone replacement graft: a report of three cases. Int J Periodontics Restorative Dent. 2010;30(2):139–49.PubMedPubMedCentralGoogle Scholar
  29. 29.
    Jung RE, et al. A randomized-controlled clinical trial evaluating clinical and radiological outcomes after 3 and 5 years of dental implants placed in bone regenerated by means of GBR techniques with or without the addition of BMP-2. Clin Oral Implants Res. 2009;20(7):660–6.PubMedCrossRefPubMedCentralGoogle Scholar
  30. 30.
    Jensen OT, et al. BMP-2/ACS/allograft for combined maxillary alveolar split/sinus floor grafting with and without simultaneous dental implant placement: report of 21 implants placed into 7 alveolar split sites followed for up to 3 years. Int J Oral Maxillofac Implants. 2014;29(1):e81–94.PubMedCrossRefGoogle Scholar
  31. 31.
    Butura CC, Galindo DF. Implant placement in alveolar composite defects regenerated with rhBMP-2, anorganic bovine bone, and titanium mesh: a report of eight reconstructed sites. Int J Oral Maxillofac Implants. 2014;29(1):e139–46.PubMedCrossRefGoogle Scholar
  32. 32.
    Bowler D, Dym H. Bone morphogenic protein: application in implant dentistry. Dent Clin North Am. 2015;59(2):493–503.PubMedCrossRefGoogle Scholar
  33. 33.
    Chan DS, et al. Wound complications associated with bone morphogenetic protein-2 in orthopaedic trauma surgery. J Orthop Trauma. 2014;28(10):599–604.PubMedCrossRefGoogle Scholar
  34. 34.
    Garrett MP, et al. Formation of painful seroma and edema after the use of recombinant human bone morphogenetic protein-2 in posterolateral lumbar spine fusions. Neurosurgery. 2010;66(6):1044–9. discussion 1049.PubMedCrossRefGoogle Scholar
  35. 35.
    Hustedt JW, Blizzard DJ. The controversy surrounding bone morphogenetic proteins in the spine: a review of current research. Yale J Biol Med. 2014;87(4):549–61.PubMedPubMedCentralGoogle Scholar
  36. 36.
    James AW, et al. A review of the clinical side effects of bone morphogenetic protein-2. Tissue Eng Part B Rev. 2016;22(4):284–97.PubMedPubMedCentralCrossRefGoogle Scholar
  37. 37.
    Lebl DR. Bone morphogenetic protein in complex cervical spine surgery: a safe biologic adjunct? World J Orthop. 2013;4(2):53–7.PubMedPubMedCentralCrossRefGoogle Scholar
  38. 38.
    Neovius E, et al. Alveolar bone healing accompanied by severe swelling in cleft children treated with bone morphogenetic protein-2 delivered by hydrogel. J Plast Reconstr Aesthet Surg. 2013;66(1):37–42.PubMedCrossRefGoogle Scholar
  39. 39.
    Woo EJ. Adverse events reported after the use of recombinant human bone morphogenetic protein 2. J Oral Maxillofac Surg. 2012;70(4):765–7.PubMedCrossRefGoogle Scholar
  40. 40.
    Zetola A, et al. Recombinant human bone morphogenetic protein-2 (rhBMP-2) in the treatment of mandibular sequelae after tumor resection. Oral Maxillofac Surg. 2011;15(3):169–74.PubMedCrossRefGoogle Scholar
  41. 41.
    Herford AS, Miller M, Signorino F. Maxillofacial defects and the use of growth factors. Oral Maxillofac Surg Clin North Am. 2017;29(1):75–88.PubMedCrossRefGoogle Scholar
  42. 42.
    Lynch SE, et al. A combination of platelet-derived and insulin-like growth factors enhances periodontal regeneration. J Clin Periodontol. 1989;16(8):545–8.PubMedCrossRefGoogle Scholar
  43. 43.
    Canalis E, McCarthy T, Centrella M. Growth factors and the regulation of bone remodeling. J Clin Invest. 1988;81(2):277–81.PubMedPubMedCentralCrossRefGoogle Scholar
  44. 44.
    Hauschka PV, et al. Growth factors in bone matrix. Isolation of multiple types by affinity chromatography on heparin-Sepharose. J Biol Chem. 1986;261(27):12665–74.PubMedGoogle Scholar
  45. 45.
    Heldin CH, Westermark B. Mechanism of action and in vivo role of platelet-derived growth factor. Physiol Rev. 1999;79(4):1283–316.PubMedCrossRefGoogle Scholar
  46. 46.
    Grotendorst GR, et al. Stimulation of granulation tissue formation by platelet-derived growth factor in normal and diabetic rats. J Clin Invest. 1985;76(6):2323–9.PubMedPubMedCentralCrossRefGoogle Scholar
  47. 47.
    Howell TH, et al. A phase I/II clinical trial to evaluate a combination of recombinant human platelet-derived growth factor-BB and recombinant human insulin-like growth factor-I in patients with periodontal disease. J Periodontol. 1997;68(12):1186–93.PubMedCrossRefGoogle Scholar
  48. 48.
    Nevins M, et al. Platelet-derived growth factor stimulates bone fill and rate of attachment level gain: results of a large multicenter randomized controlled trial. J Periodontol. 2005;76(12):2205–15.PubMedCrossRefGoogle Scholar
  49. 49.
    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 28, 40.PubMedGoogle Scholar
  50. 50.
    Nevins ML, et al. Recombinant human platelet-derived growth factor BB for reconstruction of human large extraction site defects. Int J Periodontics Restorative Dent. 2014;34(2):157–63.PubMedCrossRefPubMedCentralGoogle Scholar
  51. 51.
    Froum SJ, et al. A histomorphometric comparison of Bio-Oss alone versus Bio-Oss and platelet-derived growth factor for sinus augmentation: a postsurgical assessment. Int J Periodontics Restorative Dent. 2013;33(3):269–79.PubMedCrossRefGoogle Scholar
  52. 52.
    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.PubMedPubMedCentralGoogle Scholar
  53. 53.
    De Angelis N, De Lorenzi M, Benedicenti S. Surgical combined approach for alveolar ridge augmentation with titanium mesh and rhPDGF-BB: a 3-year clinical case series. Int J Periodontics Restorative Dent. 2015;35(2):231–7.PubMedCrossRefGoogle Scholar
  54. 54.
    Chiang T, et al. 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.PubMedCrossRefGoogle Scholar
  55. 55.
    Wallace SC, Snyder MB, Prasad H. Postextraction ridge preservation and augmentation with mineralized allograft with or without recombinant human platelet-derived growth factor BB (rhPDGF-BB): a consecutive case series. Int J Periodontics Restorative Dent. 2013;33(5):599–609.PubMedCrossRefGoogle Scholar
  56. 56.
    Funato A, et al. A novel combined surgical approach to vertical alveolar ridge augmentation with titanium mesh, resorbable membrane, and rhPDGF-BB: a retrospective consecutive case series. Int J Periodontics Restorative Dent. 2013;33(4):437–45.PubMedCrossRefGoogle Scholar
  57. 57.
    Urban IA, et al. Horizontal guided bone regeneration in the posterior maxilla using recombinant human platelet-derived growth factor: a case report. Int J Periodontics Restorative Dent. 2013;33(4):421–5.PubMedCrossRefGoogle Scholar
  58. 58.
    Steed DL. Clinical evaluation of recombinant human platelet-derived growth factor for the treatment of lower extremity ulcers. Plast Reconstr Surg. 2006;117(7 Suppl):143S–9S. discussion 150S-151S.PubMedCrossRefGoogle Scholar
  59. 59.
    Antoniades HN. Human platelet-derived growth factor (PDGF): purification of PDGF-I and PDGF-II and separation of their reduced subunits. Proc Natl Acad Sci U S A. 1981;78(12):7314–7.PubMedPubMedCentralCrossRefGoogle Scholar
  60. 60.
    Andrae J, Gallini R, Betsholtz C. Role of platelet-derived growth factors in physiology and medicine. Genes Dev. 2008;22(10):1276–312.PubMedPubMedCentralCrossRefGoogle Scholar
  61. 61.
    Steed DL. Clinical evaluation of recombinant human platelet-derived growth factor for the treatment of lower extremity diabetic ulcers. Diabetic Ulcer Study Group. J Vasc Surg. 1995;21(1):71–8. discussion 79-81.PubMedCrossRefPubMedCentralGoogle Scholar
  62. 62.
    Dohan DM, et al. Platelet-rich fibrin (PRF): a second-generation platelet concentrate. Part II: platelet-related biologic features. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2006;101(3):e45–50.PubMedCrossRefPubMedCentralGoogle Scholar
  63. 63.
    Bielecki T, Gazdzik TS, Szczepanski T. Re: “The effects of local platelet rich plasma delivery on diabetic fracture healing”. What do we use: platelet-rich plasma or platelet-rich gel? Bone. 2006;39(6):1388. author reply 1389.PubMedCrossRefPubMedCentralGoogle Scholar
  64. 64.
    Kaigler D, et al. Platelet-derived growth factor applications in periodontal and peri-implant bone regeneration. Expert Opin Biol Ther. 2011;11(3):375–85.PubMedPubMedCentralCrossRefGoogle Scholar
  65. 65.
    Marx RE, et al. Platelet-rich plasma: growth factor enhancement for bone grafts. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 1998;85(6):638–46.PubMedCrossRefPubMedCentralGoogle Scholar
  66. 66.
    Weibrich G, et al. Growth factor levels in platelet-rich plasma and correlations with donor age, sex, and platelet count. J Craniomaxillofac Surg. 2002;30(2):97–102.PubMedCrossRefPubMedCentralGoogle Scholar
  67. 67.
    Dugrillon A, et al. Autologous concentrated platelet-rich plasma (cPRP) for local application in bone regeneration. Int J Oral Maxillofac Surg. 2002;31(6):615–9.PubMedCrossRefPubMedCentralGoogle Scholar
  68. 68.
    Khairy NM, et al. Effect of platelet rich plasma on bone regeneration in maxillary sinus augmentation (randomized clinical trial). Int J Oral Maxillofac Surg. 2013;42(2):249–55.PubMedCrossRefPubMedCentralGoogle Scholar
  69. 69.
    Kutkut A, et al. Extraction socket preservation graft before implant placement with calcium sulfate hemihydrate and platelet-rich plasma: a clinical and histomorphometric study in humans. J Periodontol. 2012;83(4):401–9.PubMedCrossRefPubMedCentralGoogle Scholar
  70. 70.
    Geurs N, et al. Using growth factors in human extraction sockets: a histologic and histomorphometric evaluation of short-term healing. Int J Oral Maxillofac Implants. 2014;29(2):485–96.PubMedCrossRefPubMedCentralGoogle Scholar
  71. 71.
    Roffi A, et al. Does PRP enhance bone integration with grafts, graft substitutes, or implants? A systematic review. BMC Musculoskelet Disord. 2013;14:330.PubMedPubMedCentralCrossRefGoogle Scholar
  72. 72.
    Eskan MA, et al. Platelet-rich plasma-assisted guided bone regeneration for ridge augmentation: a randomized, controlled clinical trial. J Periodontol. 2014;85(5):661–8.PubMedCrossRefPubMedCentralGoogle Scholar
  73. 73.
    Torres J, et al. Effect of platelet-rich plasma on sinus lifting: a randomized-controlled clinical trial. J Clin Periodontol. 2009;36(8):677–87.PubMedCrossRefPubMedCentralGoogle Scholar
  74. 74.
    Tonelli P, et al. Counting of platelet derived growth factor and transforming growth factor-beta in platelet-rich-plasma used in jaw bone regeneration. Minerva Stomatol. 2005;54(1-2):23–34.PubMedPubMedCentralGoogle Scholar
  75. 75.
    Antonello Gde M, et al. Evaluation of the effects of the use of platelet-rich plasma (PRP) on alveolar bone repair following extraction of impacted third molars: prospective study. J Craniomaxillofac Surg. 2013;41(4):e70–5.PubMedCrossRefPubMedCentralGoogle Scholar
  76. 76.
    Kassolis JD, Reynolds MA. Evaluation of the adjunctive benefits of platelet-rich plasma in subantral sinus augmentation. J Craniofac Surg. 2005;16(2):280–7.PubMedCrossRefPubMedCentralGoogle Scholar
  77. 77.
    Raghoebar GM, et al. Does platelet-rich plasma promote remodeling of autologous bone grafts used for augmentation of the maxillary sinus floor? Clin Oral Implants Res. 2005;16(3):349–56.PubMedCrossRefPubMedCentralGoogle Scholar
  78. 78.
    Torres J, et al. Platelet-rich plasma may prevent titanium-mesh exposure in alveolar ridge augmentation with anorganic bovine bone. J Clin Periodontol. 2010;37(10):943–51.PubMedCrossRefPubMedCentralGoogle Scholar
  79. 79.
    Moy P, et al. Hard and soft tissue augmentation. In: Moy P, Pozzi A, Beumer J, editors. Fundmentals of implant dentistry. Chicago: Quintessence; 2016. p. 205–58.Google Scholar
  80. 80.
    Dohan DM, et al. Platelet-rich fibrin (PRF): a second-generation platelet concentrate. Part I: technological concepts and evolution. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2006;101(3):e37–44.PubMedCrossRefPubMedCentralGoogle Scholar
  81. 81.
    Davis VL, et al. Platelet-rich preparations to improve healing. Part I: workable options for every size practice. J Oral Implantol. 2014;40(4):500–10.PubMedCrossRefPubMedCentralGoogle Scholar
  82. 82.
    Khorshidi H, et al. Comparison of the mechanical properties of early leukocyte- and platelet-rich fibrin versus PRGF/Endoret membranes. Int J Dent. 2016;2016:1849207.PubMedPubMedCentralCrossRefGoogle Scholar
  83. 83.
    Schar MO, et al. Platelet-rich concentrates differentially release growth factors and induce cell migration in vitro. Clin Orthop Relat Res. 2015;473(5):1635–43.PubMedPubMedCentralCrossRefGoogle Scholar
  84. 84.
    Suttapreyasri S, Leepong N. Influence of platelet-rich fibrin on alveolar ridge preservation. J Craniofac Surg. 2013;24(4):1088–94.PubMedCrossRefPubMedCentralGoogle Scholar
  85. 85.
    Mazor Z, et al. Sinus floor augmentation with simultaneous implant placement using Choukroun’s platelet-rich fibrin as the sole grafting material: a radiologic and histologic study at 6 months. J Periodontol. 2009;80(12):2056–64.PubMedCrossRefPubMedCentralGoogle Scholar
  86. 86.
    Moussa M, El-Dahab OA, El Nahass H. Anterior maxilla augmentation using palatal bone block with platelet-rich fibrin: a controlled trial. Int J Oral Maxillofac Implants. 2016;31(3):708–15.PubMedCrossRefPubMedCentralGoogle Scholar
  87. 87.
    Yoon JS, Lee SH, Yoon HJ. The influence of platelet-rich fibrin on angiogenesis in guided bone regeneration using xenogenic bone substitutes: a study of rabbit cranial defects. J Craniomaxillofac Surg. 2014;42(7):1071–7.PubMedCrossRefPubMedCentralGoogle Scholar
  88. 88.
    Cieslik-Bielecka A, et al. L-PRP/L-PRF in esthetic plastic surgery, regenerative medicine of the skin and chronic wounds. Curr Pharm Biotechnol. 2012;13(7):1266–77.PubMedCrossRefPubMedCentralGoogle Scholar
  89. 89.
    Ghanaati S, et al. Advanced platelet-rich fibrin: a new concept for cell-based tissue engineering by means of inflammatory cells. J Oral Implantol. 2014;40(6):679–89.PubMedCrossRefPubMedCentralGoogle Scholar
  90. 90.
    Simonpieri A, et al. Simultaneous sinus-lift and implantation using microthreaded implants and leukocyte- and platelet-rich fibrin as sole grafting material: a six-year experience. Implant Dent. 2011;20(1):2–12.PubMedCrossRefPubMedCentralGoogle Scholar
  91. 91.
    Dohan Ehrenfest DM, et al. Do the fibrin architecture and leukocyte content influence the growth factor release of platelet concentrates? An evidence-based answer comparing a pure platelet-rich plasma (P-PRP) gel and a leukocyte- and platelet-rich fibrin (L-PRF). Curr Pharm Biotechnol. 2012;13(7):1145–52.PubMedCrossRefPubMedCentralGoogle Scholar
  92. 92.
    Shibli JA, et al. Composition of supra- and subgingival biofilm of subjects with healthy and diseased implants. Clin Oral Implants Res. 2008;19(10):975–82.PubMedCrossRefPubMedCentralGoogle Scholar
  93. 93.
    Ornitz DM, Itoh N. The fibroblast growth factor signaling pathway. Wiley Interdiscip Rev Dev Biol. 2015;4(3):215–66.PubMedPubMedCentralCrossRefGoogle Scholar
  94. 94.
    Kigami R, et al. FGF-2 angiogenesis in bone regeneration within critical-sized bone defects in rat calvaria. Implant Dent. 2013;22(4):422–7.PubMedCrossRefPubMedCentralGoogle Scholar
  95. 95.
    Nagayasu-Tanaka T, et al. FGF-2 promotes initial osseointegration and enhances stability of implants with low primary stability. Clin Oral Implants Res. 2016;28(3):291–7.PubMedPubMedCentralCrossRefGoogle Scholar
  96. 96.
    McCracken M, Lemons JE, Zinn K. Analysis of Ti-6Al-4V implants placed with fibroblast growth factor 1 in rat tibiae. Int J Oral Maxillofac Implants. 2001;16(4):495–502.PubMedPubMedCentralGoogle Scholar
  97. 97.
    Ting K, et al. Human NELL-1 expressed in unilateral coronal synostosis. J Bone Miner Res. 1999;14(1):80–9.PubMedCrossRefPubMedCentralGoogle Scholar
  98. 98.
    Cowan CM, et al. Nell-1 induced bone formation within the distracted intermaxillary suture. Bone. 2006;38(1):48–58.PubMedCrossRefPubMedCentralGoogle Scholar
  99. 99.
    Cowan CM, et al. Synergistic effects of Nell-1 and BMP-2 on the osteogenic differentiation of myoblasts. J Bone Miner Res. 2007;22(6):918–30.PubMedPubMedCentralCrossRefGoogle Scholar
  100. 100.
    Aghaloo T, et al. The effect of NELL1 and bone morphogenetic protein-2 on calvarial bone regeneration. J Oral Maxillofac Surg. 2010;68(2):300–8.PubMedPubMedCentralCrossRefGoogle Scholar
  101. 101.
    Grabowski G, Cornett CA. Bone graft and bone graft substitutes in spine surgery: current concepts and controversies. J Am Acad Orthop Surg. 2013;21(1):51–60.PubMedCrossRefPubMedCentralGoogle Scholar
  102. 102.
    Arrington ED, et al. Complications of iliac crest bone graft harvesting. Clin Orthop Relat Res. 1996;329:300–9.CrossRefGoogle Scholar
  103. 103.
    Bruder SP, et al. Bone regeneration by implantation of purified, culture-expanded human mesenchymal stem cells. J Orthop Res. 1998;16(2):155–62.PubMedCrossRefPubMedCentralGoogle Scholar
  104. 104.
    Bruder SP, Fink DJ, Caplan AI. Mesenchymal stem cells in bone development, bone repair, and skeletal regeneration therapy. J Cell Biochem. 1994;56(3):283–94.PubMedCrossRefPubMedCentralGoogle Scholar
  105. 105.
    Rush SM. Trinity evolution. Foot Ankle Spec. 2010;3(3):144–7.PubMedCrossRefPubMedCentralGoogle Scholar
  106. 106.
    Vanichkachorn J, et al. A prospective clinical and radiographic 12-month outcome study of patients undergoing single-level anterior cervical discectomy and fusion for symptomatic cervical degenerative disc disease utilizing a novel viable allogeneic, cancellous, bone matrix (trinity evolution) with a comparison to historical controls. Eur Spine J. 2016;25(7):2233–8.PubMedCrossRefPubMedCentralGoogle Scholar
  107. 107.
    Eastlack RK, et al. Osteocel plus cellular allograft in anterior cervical discectomy and fusion: evaluation of clinical and radiographic outcomes from a prospective multicenter study. Spine (Phila Pa 1976). 2014;39(22):E1331–7.CrossRefGoogle Scholar
  108. 108.
    Gonshor A, et al. Histologic and histomorphometric evaluation of an allograft stem cell-based matrix sinus augmentation procedure. Int J Oral Maxillofac Implants. 2011;26(1):123–31.PubMedPubMedCentralGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Section of Oral and Maxillofacial SurgeryUCLA School of DentistryLos AngelesUSA
  2. 2.Department of Oral and Maxillofacial SurgeryUniversity of WashingtonSeattleUSA

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