Skip to main content

Evolving New Strategies for Periodontal, Endodontic, and Alveolar Bone Regeneration

  • Chapter
  • First Online:
Evidence-Based Decision Making in Dentistry

Abstract

This chapter describes evolving experimental approaches that are geared toward periodontal/bone regeneration. Currently, the pinnacle of regenerative periodontal treatment is the use of bone substitutes combined with barrier membranes, which already demonstrates how far we have progressed from the old resective approaches that dominated the field. Thus, the focus of the clinical repertoire shifted from a purely surgical to biologically oriented treatment of the detrimental effects of periodontal disease and bone defects that may prevent future implant placement. The continuous presence of bacteria at the tooth-epithelium or implant-epithelium junction results in a progressive inflammatory process, which leads to the destruction of the gingival connective tissue and subsequently of the alveolar bone, periodontal ligament (PDL), and cementum on the root surface. This process, when left undisturbed, will lead eventually to the loss of the involved tooth or implant. Not only is this loss of periodontal support detrimental to the stability and function of the tooth or implant, it also hampers the restoration of the diseased area with implants following the removal of the ailing tooth/implant. Therefore, the clinical art of periodontology has been paying a tremendous amount of attention to periodontal regeneration.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 159.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Nussenbaum B, Teknos TN, Chepeha DB. Tissue engineering: the current status of this futuristic modality in head neck reconstruction. Curr Opin Otolaryngol Head Neck Surg. 2004;12(4):311–5.

    Article  PubMed  Google Scholar 

  2. Wang HL, Cooke J. Periodontal regeneration techniques for treatment of periodontal diseases. Dent Clin N Am. 2005;49:637–59.

    Article  PubMed  Google Scholar 

  3. Li H, Pujic Z, Xiao Y, Bartold PM. Identification of bone morphogenetic proteins 2 and 4 in commercial demineralized freeze-dried bone allograft preparations: pilot study. Clin Implant Dent Relat Res. 2000;2(2):110–7.

    Article  PubMed  Google Scholar 

  4. Miron RJ, Sculean A, Shuang Y, Bosshardt DD, Gruber R, Buser D, Chandad F, Zhang Y. Osteoinductive potential of a novel biphasic calcium phosphate bone graft in comparison with autographs, xenografts, and DFDBA. Clin Oral Implants Res. 2016;27:668–75.

    Article  PubMed  Google Scholar 

  5. Zhang Y, Yang S, Zhou W, Fu H, Qian L, Miron RJ. Addition of a synthetically fabricated osteoinductive biphasic calcium phosphate bone graft to BMP2 improves new bone formation. Clin Implant Dent Relat Res. 2015. doi: 10.1111/cid.12384. [Epub ahead of print].

  6. Bartold PM, McCulloch CAG, Narayanan AS, Pitaru S. Tissue engineering: a new paradigm for periodontal regeneration based on molecular and cell biology. Periodontol 2000. 2000;24:253–69.

    Article  PubMed  Google Scholar 

  7. Chen SC, Marino V, Gronthos S, Bartold PM. Location of putative stem cells in human periodontal ligament. J Periodontal Res. 2006;41:547–53.

    Article  PubMed  Google Scholar 

  8. Matsuda N, Lin WL, Kumar NM, Cho MI, Genco RJ. Mitogenic, chemotactic, and synthetic responses of rat PDL fibroblastic cells to polypeptide growth factors in vitro. J Periodontol. 1992;63:515–25.

    Article  PubMed  Google Scholar 

  9. Strayhorn CL, Garrett JS, Dunn RL, Benedict JJ, Somerman MJ. Growth factors regulate expression of osteoblast-associated genes. J Periodontol. 1999;70:1345–54.

    Article  PubMed  Google Scholar 

  10. Fujita T, Shiba H, Van Dyke TE, Kurihara H. Differential effects of growth factors and cytokines on the synthesis of SPARC, DNA, fibronectin and alkaline phosphatase activity in human PDL cells. Cell Biol Int. 2004;28:281–6.

    Article  PubMed  Google Scholar 

  11. Saygin NE, Tokiyasu Y, Giannobile WV, Somerman MJ. Growth factors regulate expression of mineral associated genes in cementoblasts. J Periodontol. 2000;71:1591–600.

    Article  PubMed  PubMed Central  Google Scholar 

  12. Hock JM, Canalis E. PDGF enhances bone cell replication but not differentiated function of osteoblasts. Endocrinology. 1994;134:1423–8.

    PubMed  Google Scholar 

  13. Mehrotra M, Krane SM, Walters K, Pilbeam C. Differential regulation of PDGF-stimulated migration and proliferation in osteoblastic cells. J Cell Biochem. 2004;93:741–52.

    Article  PubMed  Google Scholar 

  14. Takayama S, Murakami S, Miki Y, Ikezawa K, Tasaka S, Terashima A, Asano T, and Okada H. Effects of basic fibroblast growth factor on human PDL cells. J Periodont Res. 1997;32(8):667–75.

    Google Scholar 

  15. Okamoto T, Yatsuzuka N, Tanaka Y, Kan M, Yamanaka T, Sakamoto A, Takata T, Akagawa Y, Sato GH, Sato JD, Takada K. Growth and differentiation of PDL-derived cells in serum-free defined culture. In Vitro Cell Dev Biol Anim. 1997;33:302–9.

    Article  PubMed  Google Scholar 

  16. Anusaksathien O, Giannobile WV. Growth factor delivery to re-engineer periodontal tissues. Curr Pharm Biotechnol. 2002;3:129–39.

    Article  PubMed  Google Scholar 

  17. Reddi AH. Morphogenesis and tissue engineering of bone and cartilage: inductive signals, stem cells, and biomimetic biomaterials. Tissue Eng. 2000;6:351–9.

    Article  PubMed  Google Scholar 

  18. Xu WP, Shiba H, Mizuno H. Effect of BMP-4, −5 and −6 on DNA synthesis and expression of bone-related proteins in cultured human periodontal ligament cells. Cell Biol Int. 2004;28:675–82.

    Article  PubMed  Google Scholar 

  19. Taba M, Jin Q, Sugai JV, Giannobile WV. Current concepts in periodontal bioengineering. Orthod Craniofac Res. 2005;8:292–302.

    Article  PubMed  PubMed Central  Google Scholar 

  20. Teare JA, Ramoshebi LN, Ripamonti U. Periodontal tissue regeneration by recombinant human transforming growth factor-beta 3 in Papio ursinus. J Periodontal Res. 2008;43(1):1–8.

    PubMed  Google Scholar 

  21. Giannobile WV, Somerman MJ. Growth and Amelogenin-like factors in periodontal wound healing. A systematic review. Ann Periodontol. 2003;8:193–204.

    Article  PubMed  Google Scholar 

  22. Schliephake H. Bone growth factors in maxillofacial skeletal reconstruction. Int J Oral Maxillofac Surg. 2002;31:469–84.

    Article  Google Scholar 

  23. Sood S, Gupta S, Mahendra A. Gene therapy with growth factors for periodontal tissue engineering--a review. Med Oral Patol Oral Cir Bucal. 2012;17(2):e301–10.

    Article  PubMed  Google Scholar 

  24. Lin Z, Rios HF, Cochran DL. Emerging regenerative approaches for periodontal reconstruction: a systematic review from the AAP Regeneration Workshop. J Periodontol. 2015;86(2 Suppl):S134–52.

    Article  PubMed  Google Scholar 

  25. Larsson L, Decker AM, Nibali L, Pilipchuk SP, Berglundh T, Giannobile WV. Regenerative medicine for periodontal and peri-implant diseases. J Dent Res. 2016;95:255–66.

    Article  PubMed  Google Scholar 

  26. Abbayya K, Zope SA, Naduwinmani S, Pisal A, Puthanakar N. Cell- and gene- based therapeutics for periodontal regeneration. Int J Prev Med. 2015;6:110.

    Article  PubMed  PubMed Central  Google Scholar 

  27. Bartold PM, Gronthos S, Ivanovski S, Fisher A, Hutmacher DW. Tissue engineered periodontal products. J Periodontal Res. 2016;51(1):1–15.

    Article  PubMed  Google Scholar 

  28. Khoshkam V, Chan HL, Lin GH, Mailoa J, Giannobile WV, Wang HL, Oh TJ. Outcomes of regenerative treatment with rhPDGF-BB and rhFGF-2 for periodontal intra-bony defects: a systematic review and meta-analysis. J Clin Periodontol. 2015;42(3):272–80.

    Article  PubMed  Google Scholar 

  29. Kitamura M, Nakashima K, Kowashi Y, et al. Periodontal tissue regeneration using fibroblast growth factor-2: randomized controlled phase II clinical trial. PLoS One. 2008;3:e2611.

    Article  PubMed  PubMed Central  Google Scholar 

  30. Kitamura M, Akamatsu M, Kawanami M, Furuichi Y, Fujii T, Mori M, et al. Randomized placebo-controlled and controlled non-inferiority phase III trials comparing trafermin, a recombinant human fibroblast growth factor 2, and enamel matrix derivative in periodontal regeneration in intrabony defects. J Bone Miner Res. 2016;31:806–14.

    Article  PubMed  Google Scholar 

  31. de Santana RB, de Santana CM. Human intrabony defect regeneration with rhFGF-2 and hyaluronic acid – a randomized controlled clinical trial. J Clin Periodontol. 2015;42(7):658–65.

    Article  PubMed  Google Scholar 

  32. Emerton KB, Drapeau SJ, Prasad H, et al. Regeneration of periodontal tissues in non-human primates with rhGDF-5 and beta-tricalcium phosphate. J Dent Res. 2011;90:1416–21.

    Article  PubMed  Google Scholar 

  33. Lee JS, Wikesjo¨ UM, Park JC, et al. Maturation of periodontal tissues following implantation of rhGDF-5/b-TCP in one-wall intra-bony defects in dogs: 24-week histological observations. J Clin Periodontol. 2012;39:466–74.

    Article  PubMed  Google Scholar 

  34. Kempen DH, Creemers LB, Alblas J, Lu L, Verbout AJ, Yaszemski MJ, Dhert WJ. Growth factor interactions in bone regeneration. Tissue Eng Part B Rev. 2010;16(6):551–66.

    Article  PubMed  Google Scholar 

  35. Kempen DH, Lu L, Heijink A, Hefferan TE, Creemers LB, Maran A, Yaszemski MJ, Dhert WJ. Effect of local sequential VEGF and BMP-2 delivery on ectopic and orthotopic bone regeneration. Biomaterials. 2009;30(14):2816–25.

    Article  PubMed  Google Scholar 

  36. Baek WS, Yoon SR, Lim HC, Lee JS, Choi SH, Jung UW. Bone formation around rhBMP-2-coated implants in rabbit sinuses with or without absorbable collagen sponge grafting. J Periodontal Implant Sci. 2015;45(6):238–46.

    Article  PubMed  PubMed Central  Google Scholar 

  37. Lorenz C, Hoffmann A, Gross G, Windhagen H, Dellinger P, Möhwald K, Dempwolf W, Menzel H. Coating of titanium implant materials with thin polymeric films for binding the signaling protein BMP2. Macromol Biosci. 2011;11(2):234–44.

    Article  PubMed  Google Scholar 

  38. Lee EU, Lim HC, Hong JY, Lee JS, Jung UW, Choi SH. Bone regenerative efficacy of biphasic calcium phosphate collagen composite as a carrier of rhBMP-2. Clin Oral Implants Res. 2014;41(1):86–93. doi: 10.1111/jcpe.12174. Epub 2013 Oct 28.

  39. Cha JK, Lee JS, Kim MS, Choi SH, Cho KS, Jung UW. Sinus augmentation using BMP-2 in a bovine hydroxyapatite/collagen carrier in dogs. J Clin Periodontol. 2014;41(1):86–93.

    Article  PubMed  Google Scholar 

  40. Yon J, Lee JS, Lim HC, Kim MS, Hong JY, Choi SH, Jung UW. Pre-clinical evaluation of the osteogenic potential of bone morphogenetic protein-2 loaded onto a particulate porcine bone biomaterial. J Clin Periodontol. 2015;42(1):81–8.

    Article  PubMed  Google Scholar 

  41. Ishack S, Mediero A, Wilder T, Ricci JL, Cronstein BN. Bone regeneration in critical bone defects using three-dimensionally printed β-tricalcium phosphate/hydroxyapatite scaffolds is enhanced by coating scaffolds with either dipyridamole or BMP-2. J Biomed Mater Res B Appl Biomater. 2015. doi: 10.1002/jbm.b.33561. [Epub ahead of print].

  42. Giannobile WV, Lee CS, Tomala MP, Tejeda KM, Zhu Z. Platelet-Derived Growth Factor (PDGF) gene delivery for application in periodontal tissue engineering. J Periodontol. 2001;72:815–23.

    Article  PubMed  PubMed Central  Google Scholar 

  43. Lieberman JR, Chivizzani SC, Evans CH. Gene transfer approaches to the healing of bone and cartilage. Mol Ther. 2002;6:141–7.

    Article  PubMed  Google Scholar 

  44. Fang J, Zhu YY, Smiley E, Bonadio J, Rouleau JP, Goldstein SA, McCauley LK, Davidson BL, Roessler BJ. Stimulation of new bone formation by direct transfer of osteogenic plasmid genes. Proc Natl Acad Sci U S A. 1996;93:5753–8.

    Article  PubMed  PubMed Central  Google Scholar 

  45. Bonadio J, Smiley E, Patil P, Goldstein S. Localized, direct plasmid gene delivery in vivo: prolonged therapy results in reproducible tissue regeneration. Nat Med. 1999;5:753–9.

    Article  PubMed  Google Scholar 

  46. Baltzer AWA, Lattermann C, Whalen JD, Wooley P, Weiss K, Grimm M, Ghivizzani SC, Robbins PD, Evans CH. Genetic enhancement of fracture repair: healing of an experimental segmental defect by adenoviral transfer of the BMP-2 gene. Gene Ther. 2000;7:734–9.

    Article  PubMed  Google Scholar 

  47. Okubo Y, Bessho K, Fujimura K, Lizuka T, Miyatake S. Osteoinduction by bone morphogenetic protein-2 via adenoviral vector under transient immuno-suppression. Biochem Biophys Res Commun. 2000;267:382–7.

    Article  PubMed  Google Scholar 

  48. Alden TD, Beres EJ, Laurent JS, Engh JA, Das S, London SD, Jane JA, Hudson SB, Helm GA. The use of bone morphogenetic protein gene therapy in craniofacial bone repair. J Craniofac Surg. 2000;11:24–30.

    Article  PubMed  Google Scholar 

  49. Li JZ, Li H, Sasaki T, Holman D, Beres B, Dumont RJ, Pittman DD, Hankins GR, Helm GA. Osteogenic potential of five different recombinant human BMP adenoviral vectors in the rat. Gene Ther. 2003;10:1735–43.

    Article  PubMed  Google Scholar 

  50. Fang YL, Chen XG, Godbey WT. Gene delivery in tissue engineering and regenerative medicine. J Biomed Mater Res B Appl Biomater. 2015;103(8):1679–99.

    Article  PubMed  Google Scholar 

  51. Jin Q, Anusaksathien O, Webb SA, Printz MA, Giannobile WV. Engineering of tooth-supporting structures by delivery of PDGF gene therapy vectors. Mol Ther. 2004;9:519–26.

    Article  PubMed  PubMed Central  Google Scholar 

  52. Chang PC, Cirelli JA, Jin Q, Seol YJ, Sugai JV, D’Silva NJ, et al. Adenovirus encoding human platelet-derived growth factor-B delivered to alveolar bone defects exhibits safety and biodistribution profiles favorable for clinical use. Hum Gene Ther. 2009;20:486–96.

    Article  PubMed  PubMed Central  Google Scholar 

  53. Chang PC, Seol YJ, Cirelli JA, Pellegrini G, Jin Q, Franco LM, et al. PDGF-B gene therapy accelerates bone engineering and oral implant osseointegration. Gene Ther. 2010;17:95–104.

    Article  PubMed  Google Scholar 

  54. Chang PC, Dovban AS, Lim LP, Chong LY, Kuo MY, Wang CH. Dual delivery of PDGF and simvastatin to accelerate periodontal regeneration in vivo. Biomaterials. 2013;34(38):9990–7.

    Article  PubMed  Google Scholar 

  55. Dunn CA, Jin Q, Taba Jr M, Franceschi RT, Rutherford BR, Giannobile WV. BMP gene delivery for alveolar bone engineering at dental implant defects. Mol Ther. 2005;11:294–9.

    Article  PubMed  PubMed Central  Google Scholar 

  56. Chen S, Yang J, Wang H, Chao Y, Zhang C, Shen J, Zhang P. Adenovirus encoding BMP-7 immobilized on titanium surface exhibits local delivery ability and regulates osteoblast differentiation in vitro. Arch Oral Biol. 2013;58(9):1225–31.

    Article  PubMed  Google Scholar 

  57. Lu CH, Chang YH, Lin SY, Li KC, Hu YC. Recent progresses in gene delivery-based bone tissue engineering. Biotechnol Adv. 2013;31(8):1695–706.

    Article  PubMed  Google Scholar 

  58. Kaigler D, Wang Z, Horger K, Mooney DJ, Krebsbach PH. VEGF scaffolds enhance angiogenesis and bone regeneration in irradiated osseous defects. J Bone Miner Res. 2006;21(5):735–44.

    Article  PubMed  Google Scholar 

  59. Kaigler D, Silva EA, Mooney DJ. Guided bone regeneration using injectable vascular endothelial growth factor delivery gel. J Periodontol. 2013;84(2):230–8.

    Article  PubMed  Google Scholar 

  60. D’Mello SR, Elangovan S, Hong L, Ross RD, Sumner DR, Salem AK. A pilot study evaluating combinatorial and simultaneous delivery of polyethylenimine-plasmid DNA complexes encoding for VEGF and PDGF for bone regeneration in calvarial bone defects. Curr Pharm Biotechnol. 2015;16(7):655–60.

    Article  PubMed  PubMed Central  Google Scholar 

  61. Pagni G, Kaigler D, Rasperini G, Avila-Ortiz G, Bartel R, Giannobile WV. Bone repair cells for craniofacial regeneration. Adv Drug Deliv Rev. 2012;64(12):1310–9.

    Article  PubMed  PubMed Central  Google Scholar 

  62. Risbud MV, Shapiro IM. Stem cells in craniofacial and dental tissue engineering. Orthod Craniofac Res. 2005;8:54–9.

    Article  PubMed  Google Scholar 

  63. Bianco P, Riminucci M, Gronthos S, Robey PG. Bone marrow stromal stem cells: nature, biology, and potential applications. Stem Cells. 2001;19:180–92.

    Article  PubMed  Google Scholar 

  64. Bruder SP, Kraus KH, Goldberg VM, Kadiyala S. The effect of implants loaded with autologous mesenchymal stem cells on the healing of canine segmental bone defects. J Bone Joint Surg Am. 1998;80:985–96.

    Article  PubMed  Google Scholar 

  65. Bruder SP, Jaiswal N, Ricalton NS, Mosca JD, Kraus KH, Kadiyala S. Mesenchymal stem cells in osteobiology and applied bone regeneration. Clin Orthop Relat Res. 1998;355(Suppl):S247–56.

    Article  Google Scholar 

  66. Krebsbach PH, Mankani MH, Satomura K, Kuznetsov SA, Robey PG. Repair of craniotomy defects using bone marrow stromal cells. Transplantation. 1998;66:1272–8.

    Article  PubMed  Google Scholar 

  67. Quarto R, Mastrogiacomo M, Cancedda R, Kutepov SM, Mukhachev V, Lavroukov A, Kon E, Marcacci M. Repair of large bone defects with the use of autologous bone marrow stromal cells. N Engl J Med. 2001;344:385–6.

    Article  PubMed  Google Scholar 

  68. Schantz JT, Hutmacher DW, Lam CX, Brinkmann M, Wong KM, Lim TC, Chou N, Guldberg RE, Teoh SH. Repair of calvarial defects with customized tissue-engineered bone grafts II. Evaluation of cellular efficiency and efficacy in vivo. Tissue Eng. 2003;9 Suppl 1:S127–39.

    Article  PubMed  Google Scholar 

  69. Kawaguchi H, Hirachi A, Hasegawa N, Iwata T, Hamaguchi H, Shiba H, Takata T, Kato Y, Kurihara H. Enhancement of periodontal tissue regeneration by transplantation of bone marrow mesenchymal stem cells. J Periodontol. 2004;5:1281–7.

    Article  Google Scholar 

  70. Sankaranarayanan S, Jetty N, Gadagi JS, Preethy S, Abraham SJ. Periodontal regeneration by autologous bone marrow mononuclear cells embedded in a novel thermo reversible gelation polymer. J Stem Cells. 2013;8(2):99–103.

    PubMed  Google Scholar 

  71. Paknejad M, Eslaminejad MB, Ghaedi B, Rokn AR, et al. Isolation and assessment of mesenchymal stem cells derived from bone marrow: histologic and histomorphometric study in a canine periodontal defect. J Oral Implantol. 2015;41(3):284–91.

    Article  PubMed  Google Scholar 

  72. Seo B, Miura M, Gronthos S, Bartold PM, Batouli S, Brahim J, Young M, Robey PG, Wang CY, Shi S. Investigation of multipotent postnatal stem cells from human PDL. Lancet. 2004;364:149–55.

    Article  PubMed  Google Scholar 

  73. Trubiani O, Di Primo R, Traini T, Pizzicannella J, Scarano A, Piattelli A, Caputi S. Morphological and cytofluorimetric analysis of adult mesenchymal stem cells expanded ex vivo from PDL. Int J Immunopathol Pharmacol. 2005;18:213–21.

    PubMed  Google Scholar 

  74. Seo BM, Miura M, Sonoyama W, Coppe C, Stanyon R, Shi S. Recovery of stem cells from cryopreserved periodontal ligament. J Dent Res. 2005;84(10):907–12.

    Article  PubMed  Google Scholar 

  75. Kramer PR, Nares S, Kramer SF, Grogan D, Kaiser M. Mesenchymal stem cells acquire characteristics of cells in the periodontal ligament in vitro. J Dent Res. 2004;83:27–34.

    Article  PubMed  Google Scholar 

  76. Dogan A, Ozdemir A, Kubar A, Oygur T. Healing of artificial fenestration defects by seeding of fibroblast-like cells derived from regenerated periodontal ligament in a dog: a preliminary study. Tissue Eng. 2003;9:1189–96.

    Article  PubMed  Google Scholar 

  77. Nakahara T, Nakamura T, Kobayashi E, Kuremoto K, Matsuno T, Tabata Y, Eto K, Shimizu Y. In situ tissue engineering of periodontal tissues by seeding with periodontal ligament-derived cells. Tissue Eng. 2004;10:537–44.

    Article  PubMed  Google Scholar 

  78. Murano Y, Ota M, Katayama A, Sugito H, Shibukawa Y, Yamada S. Periodontal regeneration following transplantation of proliferating tissue derived from PDL into class III furcation defects in dogs. Biomed Res. 2006;27(3):139–47.

    Article  PubMed  Google Scholar 

  79. Hasegawa M, Yamato M, Kikuchi A, Okano T, Ishikawa I. Human periodontal ligament cell sheets can regenerate periodontal ligament tissue in an athymic rat model. Tissue Eng. 2005;11:469–78.

    Article  PubMed  Google Scholar 

  80. Akizuki T, Oda S, Komaki M, Tsuchioka H, Kawakatsu N, Kikuchi A, Yamato M, Okano T, Ishikawa I. Application of periodontal ligament cell sheet for periodontal regeneration: a pilot study in beagle dogs. J Periodontal Res. 2005;40:245–51.

    Article  PubMed  Google Scholar 

  81. Iwata T, Yamato M, Tsuchioka H, Takagi R, Mukobata S, Washio K, Okano T, Ishikawa I. Periodontal regeneration with multi-layered periodontal ligament-derived cell sheets in a canine model. Biomaterials. 2009;30(14):2716–23.

    Article  PubMed  Google Scholar 

  82. Gomez Flores M, Hasegawa M, Yamato M, Takagi R, Okano T, Ishikawa I. Cementum-periodontal ligament complex regeneration using the cell sheet technique. J Periodontal Res. 2008;43(3):364–71.

    Article  PubMed  Google Scholar 

  83. Ishikawa I, Iwata T, Washio K, Okano T, Nagasawa T, Iwasaki K, Ando T. Cell sheet engineering and other novel cell-based approaches to periodontal regeneration. Periodontol 2000. 2009;51:220–38.

    Google Scholar 

  84. Iwata T, Washio K, Yoshida T, Ishikawa I, Ando T, Yamato M, Okano T. Cell sheet engineering and its application for periodontal regeneration. J Tissue Eng Regen Med. 2015;9(4):343–56.

    Article  PubMed  Google Scholar 

  85. Grzesik WJ, Kuznetsov SA, Uzawa K, Mankani M, Robey PG, Yamaguchi M. Normal human cementum-derived cells: Isolation, clonal expansion, and in vitro and in vivo characterization. J Bone Miner Res. 1998;13:1547–54.

    Article  PubMed  Google Scholar 

  86. D’Errico JA, Ouyang H, Berry JH, MacNeill RL, Strayhorn C, Imperiale MJ, Harris NL, Goldberg H, Somerman MJ. Immortalized cementoblasts and PDL cells in culture. Bone. 1999;25:39–47.

    Article  PubMed  Google Scholar 

  87. Saito M, Handa K, Kiyono T, Hattori S, Yokoi T, Tsubakimoyo T, Harada H, Noguchi T, Toyoda M, Sato S, Teranaka T. Immortalization of cementoblast progenitor cells with Bmi-1 and TERT. J Bone Miner Res. 2005;20:50–7.

    Article  PubMed  Google Scholar 

  88. Jin QM, Zhao M, Webb SA, Berry JE, Somerman MJ, Giannobile WV. Cementum engineering with three-dimensional polymer scaffolds. J Biomed Mater Res A. 2003;67:54–60.

    Article  PubMed  PubMed Central  Google Scholar 

  89. Zhao M, Jin Q, Berry JE, Nociti Jr FH, Giannobile WV, Somerman MJ. Cementoblast delivery for periodontal tissue engineering. J Periodontol. 2004;75:154–61.

    Article  PubMed  PubMed Central  Google Scholar 

  90. Mizuno H, Hata K, Kojima K, Bonasser IJ, Vacanti CA, Ueda M. A novel approach to regenerating periodontal tissue by grafting autologous cultured periosteum. Tissue Eng. 2006;12(5):1227–35.

    Article  PubMed  Google Scholar 

  91. Ribeiro FV, Suaid FF, Ruiz KG, Rodrigues TL, Carvalho MD, Nociti FH, Sallum EA, Casati MZ. Peri-implant reconstruction using autologous periosteum-derived cells and guided bone regeneration. J Clin Periodontol. 2010;37(12):1128–36.

    Article  PubMed  Google Scholar 

  92. Kaigler D, Pagni G, Park CH, Braun TM, Holman LA, Yi E, Tarle SA, Bartel RL, Giannobile WV. Stem cell therapy for craniofacial bone regeneration: a randomized, controlled feasibility trial. Cell Transplant. 2013;22(5):767–77.

    Article  PubMed  PubMed Central  Google Scholar 

  93. Park JY, Yang C, Jung IH, Lim HC, Lee JS, Jung UW, Seo YK, Park JK, Choi SH. Regeneration of rabbit calvarial defects using cells-implanted nano-hydroxyapatite coated silk scaffolds. Biomater Res. 2015;19:7.

    Article  PubMed  PubMed Central  Google Scholar 

  94. Park JC, Oh SY, Lee JS, Park SY, Choi EY, Cho KS, Kim CS. In vivo bone formation by human alveolar-bone-derived mesenchymal stem cells obtained during implant osteotomy using biphasic calcium phosphate ceramics or Bio-Oss as carriers. J Biomed Mater Res B Appl Biomater. 2016;104:515–24.

    Article  PubMed  Google Scholar 

  95. Yan XZ, Yang F, Jansen JA, de Vries RB, van den Beucken JJ. Cell-based approaches in periodontal regeneration: a systematic review and meta-analysis of periodontal defect models in animal experimental work. Tissue Eng Part B Rev. 2015;21(5):411–26.

    Article  PubMed  Google Scholar 

  96. Duan X, Tu Q, Zhang J, Ye J, Sommer C, Mostoslavsky G, Kaplan D, Yang P, Chen J. Application of induced pluripotent stem (iPS) cells in periodontal tissue regeneration. J Cell Physiol. 2011;226(1):150–7.

    Article  PubMed  PubMed Central  Google Scholar 

  97. Du M, Duan X, Yang P. Induced pluripotent stem cells and periodontal regeneration. Curr Oral Health Rep. 2015;2(4):257–65.

    Article  PubMed  PubMed Central  Google Scholar 

  98. Umezaki Y, Hashimoto Y, Nishishita N, Kawamata S, Baba S. Human gingival integration-free iPSCs; a source for MSC-like cells. Int J Mol Sci. 2015;16(6):13633–48.

    Article  PubMed  PubMed Central  Google Scholar 

  99. Hynes K, Menichanin D, Bright R, Ivanovski S, Hutmacher DW, Gronthos S, Bartold PM. Induced pluripotent stem cells: a new frontier for stem cells in dentistry. J Dent Res. 2015;94(11):1508–15.

    Article  PubMed  Google Scholar 

  100. Lieberman JR, Daluiski A, Stevenson S, Wu L, McAllister P, Lee YP, Kabo JM, Finerman GA, Berk AJ, Witte ON. The effect of regional gene therapy with bone morphogenetic protein-2-producing bone-marrow cells on the repair of segmental femoral defects in rats. J Bone Joint Surg Am. 1999;81:905–17.

    Article  PubMed  Google Scholar 

  101. Chang S, Chuang H, Chen YR, Yang LC, Chen JK, Mardini S, Chung HY, Lu YL. Cranial repair using BMP-2 gene engineered bone marrow stromal cells. J Surg Res. 2004;119:85–91.

    Article  PubMed  Google Scholar 

  102. Rutherford RB, Moalli M, Franceschi RT, Wang D, Gu K, Krebsbach PH. Bone morphogenetic protein-transduced human fibroblasts convert to osteoblasts and form bone in vivo. Tissue Eng. 2002;8:441–52.

    Article  PubMed  Google Scholar 

  103. Krebsbach PH, Gu K, Franceschi RT, Rutherford RB. Gene therapy-directed osteogenesis: BMP-7-transduced human fibroblasts form bone in vivo. Hum Gene Ther. 2000;11:1201–10.

    Article  PubMed  Google Scholar 

  104. Lee JY, Musgrave D, Pelinkovic D, Fukushima K, Cummins J, Usas A, Robbins P, Fu FH, Huard J. Effect of BMP-2-expressing muscle derived cells on healing of critical-sized bone defects in mice. J Bone Joint Surg Am. 2001;83-A:1032–9.

    Article  PubMed  Google Scholar 

  105. Peterson B, Zhang J, Iglesias R, Kabo M, Hedrick M, Benhaim P, Lieberman JR. Healing of critically sized femoral defects, using genetically modified mesenchymal stem cells from human adipose tissue. Tissue Eng. 2005;11:120–9.

    Article  PubMed  Google Scholar 

  106. Zhao M, Zhao Z, Koh JT, Jin T, Franceschi RT. Combinatorial gene therapy for bone regeneration: cooperative interactions between adenovirus vectors expressing bone morphogenetic proteins 2, 4, and 7. J Cell Biochem. 2005;95:1–16.

    Article  PubMed  Google Scholar 

  107. Jin QM, Anusaksathien O, Webb SA, Rutherford RB, Giannobile WV. Gene therapy of bone morphogenetic protein for periodontal tissue engineering. J Periodontol. 2003;74:202–13.

    Article  PubMed  PubMed Central  Google Scholar 

  108. Chen YL, Chen PK, Jeng LB, et al. Periodontal regeneration using ex vivo autologous stem cells engineered to express the BMP-2 gene: an alternative to alveolaplasty. Gene Ther. 2008;15:1469–77.

    Article  PubMed  Google Scholar 

  109. Huang YC, Kaigler D, Rice KG, Krebsbach PH, Mooney DJ. Combined angiogenic and osteogenic factor delivery enhances bone marrow stromal cell-driven bone regeneration. J Bone Miner Res. 2005;20:848–57.

    Article  PubMed  Google Scholar 

  110. Edwards PC, Ruggiero S, Fantasia J, Burakoff R, Moorji SM, Paric E, Razzano P, Grande DA, Mason JM. Sonic hedgehog gene-enhanced tissue engineering for bone regeneration. Gene Ther. 2006;12(1):75–8.

    Article  Google Scholar 

  111. Zhu Z, Lee CS, Tejeda KM, Giannobile WV. Gene transfer and expression of PDGFs modulate periodontal cellular activity. J Dent Res. 2001;80:892–7.

    Article  PubMed  PubMed Central  Google Scholar 

  112. Giannobile WV, Hemandez RA, Finkelman RD, Ryan S, Kiritsy CP, D’Andrea M, Lynch SE. Comparative effects of platelet-derived growth factor-BB and insulin-like growth factor-I, individually and in combination, on periodontal regeneration in Macaca fascicularis. J Periodontal Res. 1996;31:301–12.

    Article  PubMed  Google Scholar 

  113. Anusaksathien O, Jin Q, Zhao M, Somerman MJ, Giannobile WV. Effect of sustained gene delivery of PDGF or its antagonist (PDGF-1308) on tissue-engineered cementum. J Periodontol. 2004;75:429–40.

    Article  PubMed  PubMed Central  Google Scholar 

  114. Samee M, Kasugai S, Kondo H, Ohya K, Shimokawa H, Kuroda S. Bone morphogenetic protein-2 (BMP-2) and vascular endothelial growth factor (VEGF) transfection to human periosteal cells enhances osteoblast differentiation and bone formation. J Pharmacol Sci. 2008;108(1):18–31.

    Article  PubMed  Google Scholar 

  115. Fux C, Mitta B, Kramer BP, Fussenegger M. Dual-regulated expression of C/EBP-alpha and BMP-2 enables differential differentiation of C2C12 cells into adipocytes and osteoblasts. Nucleic Acids Res. 2004;32:e1.

    Article  PubMed  PubMed Central  Google Scholar 

  116. Koh J, Ge C, Wang Z, Krebsbach P, Franceschi RT. Regulated BMP-2 gene therapy for bone regeneration. J Bone Miner Res. 2005;20 Suppl 1:S322.

    Google Scholar 

  117. Gafni Y, Pelled G, Zilberman Y, Turgeman G, Apparailly F, Yotvat H, Galun E, Gazit Z, Jorgensen C, Gazit D. Gene therapy platform for bone regeneration using an exogenously regulated, AAV-2-based gene expression system. Mol Ther. 2004;9:587–95.

    Article  PubMed  Google Scholar 

  118. Rasperini G, Pilipchuk SP, Flanagan CL, Park CH, Pagni G, Hollister SJ, Giannobile WV. 3D-printed bioresorbable scaffold for periodontal repair. J Dent Res. 2015;94(9 Suppl):153S–7.

    Article  PubMed  Google Scholar 

  119. Obregon F, Vaquette C, Ivanovski S, Hutmacher DW, Bertassoni LE. Three-dimensional bioprinting for regenerative dentistry and craniofacial tissue engineering. J Dent Res. 2015;94(9 Suppl):143S–52.

    Article  PubMed  Google Scholar 

  120. Park CH, Rios HF, Jin Q, Sugai JV, Padial-Molina M, Taut AD, Flanagan CL, Hollister SJ, Giannobile WV. Tissue engineering bone-ligament complexes using fiber-guiding scaffolds. Biomaterials. 2012;33(1):137–45.

    Article  PubMed  Google Scholar 

  121. Goh BT, Teh LY, Tan DB, Zhang Z, Teoh SH. Novel 3D polycaprolactone scaffold for ridge preservation: a pilot randomized controlled clinical trial. Clin Oral Implants Res. 2015;26(3):271–7.

    Article  PubMed  Google Scholar 

  122. Chen FM, Shelton RM, Jin Y, Chapple IL. Localized delivery of growth factors for periodontal tissue regeneration: role, strategies, and perspectives. Med Res Rev. 2009;29(3):472–513.

    Article  PubMed  Google Scholar 

  123. Hammarstrom L. Enamel matrix, cementum development and regeneration. J Clin Periodontol. 1997;24:658–68.

    Article  PubMed  Google Scholar 

  124. Hammarstrom L, Heijl L, Gestrelius S. Periodontal regeneration in a buccal dehiscence model in monkeys after application of enamel matrix proteins. J Clin Periodontol. 1997;24:669–77.

    Article  PubMed  Google Scholar 

  125. Gestrelius S, Lyngstadaas SP, Hammarstrom L. Emdogain – periodontal regeneration based on biomimicry. Clin Oral Investig. 2000;4:120–5.

    Article  PubMed  Google Scholar 

  126. Heijl L, Heden G, Svardstrom G, Ostgren A. Enamel matrix derivative (EMDOGAIN) in the treatment of intrabony periodontal defects. J Clin Periodontol. 1997;24:705–14.

    Article  PubMed  Google Scholar 

  127. Sculean A, Pietruska M, Schwarz F, Willershausen B, Arweiler NB, Auschill TM. Healing of human intrabony defects following regenerative periodontal therapy with an enamel matrix protein derivative alone or combined with a bioactive glass. A controlled clinical study. J Clin Periodontol. 2005;32:111–7.

    Article  PubMed  Google Scholar 

  128. Koop R, Merheb J, Quirynen M. Periodontal regeneration with enamel matrix derivative in reconstructive periodontal therapy: a systematic review. J Periodontol. 2012;83(6):707–20.

    Article  PubMed  Google Scholar 

  129. Miron RJ, Guillemette V, Zhang Y, Chandad F, Sculean A. Enamel matrix derivative in combination with bone grafts: a review of the literature. Quintessence Int. 2014;45(6):475–87.

    PubMed  Google Scholar 

  130. Matarasso M, Iorio-Siciliano V, Blasi A, Ramaglia L, Salvi GE, Sculean A. Enamel matrix derivative and bone grafts for periodontal regeneration of intrabony defects. A systematic review and meta-analysis. Clin Oral Investig. 2015;19(7):1581–93.

    Article  PubMed  Google Scholar 

  131. Ivanovic A, Nikou G, Miron RJ, Nikolidakis D, Sculean A. Which biomaterials may promote periodontal regeneration in intrabony periodontal defects? A systematic review of pre-clinical studies. Quintessence Int. 2014;45:385–95.

    PubMed  Google Scholar 

  132. Sculean A, Nikolidakis D, Nikou G, Ivanovic A, Chapple IL, Stavropoulos A. Biomaterials for promoting periodontal regeneration in human intrabony defects: a systematic review. Periodontol 2000. 2015;68(1):182–216.

    Article  PubMed  Google Scholar 

  133. Gestrelius S, Andersson C, Lidstrom D, Hammarstrom I, Somerman MJ. In vitro studies on PDL cells and enamel matrix derivative. J Clin Periodontol. 1997;24:685–92.

    Article  PubMed  Google Scholar 

  134. Rincon JC, Xiao Y, Young WG, Bartold PM. Enhanced proliferation, attachment and osteopontin expression by porcine periodontal cells exposed to Emdogain. Arch Oral Biol. 2005;50(12):1047–54.

    Article  PubMed  Google Scholar 

  135. Chong CH, Carnes DL, Moritz AJ, Oates T, Ryu O, Simmer J, Cochran DL. Human periodontal fibroblast response to enamel matrix derivative, amelogenin, and PDGF-BB. J Periodontol. 2006;77(7):1242–52.

    Article  PubMed  Google Scholar 

  136. Hagewald S, Pischon N, Jawor P, Bernimoulin JP, Zimmermann B. Effects of enamel matrix derivative on proliferation and differentiation of primary osteoblasts. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2004;98(2):243–9.

    Article  PubMed  Google Scholar 

  137. Tokiyasu Y, Takata T, Saygin E, Somerman M. Enamel factors regulate expression of genes associated with cementoblasts. J Periodontol. 2000;71:1829–39.

    Article  PubMed  Google Scholar 

  138. Kawase T, Okuda H, Momose M, Kato Y, Yoshie H, Burns DM. Enamel matrix derivative (EMDOGAIN) rapidly stimulates phosphorylation of the MAP kinase family and nuclear accumulation of Smad2 in both oral epithelial and fibroblastic human cells. J Periodontal Res. 2001;36:367–76.

    Article  PubMed  Google Scholar 

  139. Weinberg E, Topaz M, Dard M, Lyngstadaas P, Nemcovsky C, Weinreb M. Differential effects of prostaglandin E(2) and enamel matrix derivative on the proliferation of human gingival and dermal fibroblasts and gingival keratinocytes. J Periodontal Res. 2010;45(6):731–40.

    Article  PubMed  Google Scholar 

  140. Keila S, Nemcovsky C, Moses O, Artzi Z, Weinreb M. In-vitro effects of enamel matrix proteins on rat bone marrow cells and gingival fibroblasts. J Dent Res. 2004;83:134–8.

    Article  PubMed  Google Scholar 

  141. Bosshardt DD. Biological mediators and periodontal regeneration: a review of enamel matrix proteins at the cellular and molecular levels. J Clin Periodontol. 2008;35(8 Suppl):87–105.

    Article  PubMed  Google Scholar 

  142. Grandin HM, Gemperli AC, Dard M. Enamel matrix derivative: a review of cellular effects in vitro and a model of molecular arrangement and functioning. Tissue Eng Part B Rev. 2012;18(3):181–202.

    Article  PubMed  Google Scholar 

  143. Weinreb M, Nemcovsky CE. In vitro models for evaluation of periodontal wound healing/regeneration. Periodontol 2000. 2015;68(1):41–54.

    Article  PubMed  Google Scholar 

  144. Parkar MH, Tonetti M. Gene expression profiles of periodontal ligament cells treated with Enamel Matrix Proteins in vitro: analysis using cDNA arrays. J Periodontol. 2004;75(11):1539–46.

    Article  PubMed  Google Scholar 

  145. Carinci F, Piattelli A, Guida L, Perrotti V, Laino G, Oliva A, Annunziata M, Palmieri A, Pezzetti F. Effects of Emdogain on osteoblast gene expression. Oral Dis. 2006;12(3):329–42.

    Article  PubMed  Google Scholar 

  146. Reseland JE, Reppe S, Larsen AM, Berner HS, Reinholt FP, Gautvik KM, Slaby I, Lyngstadaas SP. The effect of enamel matrix derivative on gene expression in osteoblasts. Eur J Oral Sci. 2006;114 suppl 1:205–11.

    Article  PubMed  Google Scholar 

  147. Zeldich E, Koren R, Dard M, Weinberg E, Weinreb M, Nemcovsky CE. Enamel matrix derivative induces the expression of tissue inhibitor of matrix metalloproteinase-3 in human gingival fibroblasts via extracellular signal-regulated kinase. J Periodontal Res. 2010;45(2):200–6.

    Article  PubMed  Google Scholar 

  148. Miron RJ, Bosshardt DD, Zhang Y, Buser D, Sculean A. Gene array of primary human osteoblasts exposed to enamel matrix derivative in combination with a natural bone mineral. Clin Oral Investig. 2013;17(2):405–10.

    Article  PubMed  Google Scholar 

  149. Yan XZ, Rathe F, Gilissen C, van der Zande M, Veltman J, Junker R, Yang F, Jansen JA, Walboomers XF. The effect of enamel matrix derivative (Emdogain®) on gene expression profiles of human primary alveolar bone cells. J Tissue Eng Regen Med. 2014;8(6):463–72.

    Article  PubMed  Google Scholar 

  150. Miron RJ, Shuang Y, Sculean A, Buser D, Chandad F, Zhang Y. Gene array of PDL cells exposed to Osteogain in combination with a bone grafting material. Clin Oral Investig. (2016). doi:10.1007/s00784-015-1702-2. [Epub ahead of print].

  151. Johnson DL, Carnes D, Steffensen B, Cochran DL. Cellular effects of enamel matrix derivative are associated with different molecular weight fractions following separation by size-exclusion chromatography. J Periodontol. 2009;80(4):648–56.

    Article  PubMed  PubMed Central  Google Scholar 

  152. Villa O, Brookes SJ, Thiede B, Heijl L, Lyngstadaas SP, Reseland JE. Subfractions of enamel matrix derivative differentially influence cytokine secretion from human oral fibroblasts. J Tissue Eng. 2015;19:6.

    Google Scholar 

  153. Stout BM, Alent BJ, Pedalino P, Holbrook R, Gluhak-Heinrich J, Cui Y, Harris MA, Gemperli AC, Cochran DL, Deas DE, Harris SE. Enamel matrix derivative: protein components and osteoinductive properties. J Periodontol. 2014;85(2):e9–17.

    Article  PubMed  Google Scholar 

  154. Andrukhov O, Gemperli AC, Tang Y, Howald N, Dard M, Falkensammer F, Moritz A, Rausch-Fan X. Effect of different enamel matrix derivative proteins on behavior and differentiation of endothelial cells. Dent Mater. 2015;31(7):822–32.

    Article  PubMed  Google Scholar 

  155. Amin HD, Olsen I, Knowles J, Dard M, Donos N. Interaction of enamel matrix proteins with human periodontal ligament cells. Clin Oral Investig. 2016;20(2):339–47.

    Article  PubMed  Google Scholar 

  156. Miron RJ, Bosshardt DD, Buser D, Zhang Y, Tugulu S, Gemperli A, Dard M, Caluseru OM, Chandad F, Sculean A. Comparison of the capacity of enamel matrix derivative gel and enamel matrix derivative in liquid formulation to adsorb to bone grafting materials. J Periodontol. 2015;86(4):578–87.

    Article  PubMed  Google Scholar 

  157. Zhang Y, Jing D, Buser D, Sculean A, Chandad F, Miron RJ. Bone grafting material in combination with Osteogain for bone repair: a rat histomorphometric study. Clin Oral Investig. 2016;20:589–95.

    Article  PubMed  Google Scholar 

  158. Hagewald S, Spahr A, Rompola E, Haller B, Heijl L, Bernimoulin JP. Comparative study of Emdogain and coronally advanced flap technique in the treatment of human gingival recessions. A prospective controlled clinical study. J Clin Periodontol. 2002;29(1):35–41.

    Article  PubMed  Google Scholar 

  159. Cueva MA, Boltchi FE, Halmon WW, Nunn ME, Rivera-Hidalgo F, Rees T. A comparative study of coronally advanced flaps with and without the addition of enamel matrix derivative in the treatment of marginal tissue recession. J Periodontol. 2004;75:949–56.

    Article  PubMed  Google Scholar 

  160. Tonetti MS, Fourmousis I, Suvan J, Cortellini P, Bragger U, Lang NP. Healing, post-operative morbidity and patient perception of outcomes following regenerative therapy of deep intrabony defects. J Clin Periodontol. 2004;31(12):1092–8.

    Article  PubMed  Google Scholar 

  161. Zeldich E, Koren R, Nemcovsky C, Weinreb M. Enamel Matrix Derivative stimulates the proliferation of human gingival fibroblasts in an ERK-dependent manner. J Dent Res. 2007;86(1):41–6.

    Article  PubMed  Google Scholar 

  162. Zeldich E, Koren R, Dard M, Nemcovsky C, Weinreb M. EGFR in Enamel Matrix Derivative-induced gingival fibroblast mitogenesis. J Dent Res. 2008;87(9):850–5.

    Article  PubMed  Google Scholar 

  163. Zeldich E, Koren R, Dard M, Nemcovsky C, Weinreb M. Enamel Matrix Derivative Protects Human Gingival Fibroblasts from TNF-induced apoptosis by inhibiting caspase activation. J Cell Physiol. 2007;213(3):750–8.

    Article  PubMed  Google Scholar 

  164. Villa O, Wohlfahrt JC, Mdla I, Petzold C, Reseland JE, Snead ML, Lyngstadaas SP. Proline-rich peptide mimics effects of enamel matrix derivative on rat oral mucosa incisional wound healing. J Periodontol. 2015;86(12):1386–95.

    Article  PubMed  Google Scholar 

  165. Maymon-Gil T, Weinberg E, Nemcovsky C, Weinreb M. Enamel matrix derivative promotes healing of a surgical wound in the rat oral mucosa. J Periodontol. 2016:1–16.[Epub ahead of print].

    Google Scholar 

  166. Cattaneo V, Rota C, Silvestri M, Piacentini C, Forlino A, Gallanti A, Rasperini G, Cetta G. Effect of enamel matrix derivative on human periodontal fibroblasts: proliferation, morphology and root surface colonization. An in vitro study. J Periodontol Res. 2003;38:568–74.

    Article  Google Scholar 

  167. Haase HR, Bartold PM. Enamel matrix derivative induces matrix synthesis by cultured human periodontal fibroblast cells. J Periodontol. 2001;72:341–8.

    Article  PubMed  Google Scholar 

  168. Brett PM, Parkar M, Olsen I, Tonetti M. Expression profiling of periodontal ligament cells stimulated with enamel matrix proteins in vitro: a model for tissue regeneration. J Dent Res. 2002;81(11):776–83.

    Article  PubMed  Google Scholar 

  169. Lieberman JR, Daluiski A, Einhorn TA. The role of growth factors in the repair of bone. J Bone Joint Surg. 2002;84-A:1032–44.

    Article  PubMed  Google Scholar 

  170. Werner S, Grose R. Regulation of wound healing by growth factors and cytokines. Physiol Rev. 2003;83:835–70.

    PubMed  Google Scholar 

  171. Chaudhary LR, Hofmeister AM, Hruska KA. Differential growth factor control of bone formation through osteoprogenitor differentiation. Bone. 2004;34:402–11.

    Article  PubMed  Google Scholar 

  172. Naik AA, Xie C, Zuscik MJ, Kingsley P, Schwarz EM, Awad H, Guldberg R, Drissi H, Puzas JE, Boyce B, Zhang X, O’Keefe RJ. Reduced COX-2 expression in aged mice is associated with impaired fracture healing. J Bone Miner Res. 2009 Feb;24(2):251–64. doi:10.1359/jbmr.081002.

  173. Kirker-Head CA. Potential applications and delivery strategies for bone morphogenetic proteins. Adv Drug Deliv Rev. 2000;43:65–92.

    Article  PubMed  Google Scholar 

  174. Sawai K, Mori K, Mukoyama M, Sugawara A, Suganami T, Koshikawa M, Yahata K, Makino H, Nagae T, Fujinaga Y, Yokoi H, Yoshioka T, Yoshimoto A, Tanaka I, Nakao K. Angiogenic protein Cyr61 is expressed by podocytes in anti-Thy-1 glomerulonephritis. J Am Soc Nephrol. 2003 May;14(5):1154–63.

    Google Scholar 

  175. Boyne PJ, Lilly LC, Marx RE, Moy PK, Nevins M, Spagnoli DB, Triplett RG. De novo bone induction by recombinant human bone morphogenetic protein-2 (rhBMP-2) in maxillary sinus floor augmentation. J Oral Maxillofac Surg. 2005;63:1693–707.

    Article  PubMed  Google Scholar 

  176. Triplett RG, Nevins M, Marx RE, Spagnoli DB, Oates TW, Moy PK, Boyne PJ. 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;67:1947–60.

    Article  PubMed  Google Scholar 

  177. Lynch SE, de Castilla GR, Williams RC, Kiritsy CP, Howell TH, Reddy MS, Antoniades HN. The effects of short-term application of a combination of platelet-derived and insulin-like growth factors on periodontal wound healing. J Periodontol. 1991;62:458–67.

    Article  PubMed  Google Scholar 

  178. Lynch SE, Williams RC, Polson AM, Howell TH, Reddy MS, Zappa UE, Antoniades HN. A combination of platelet-derived and insulin-like growth factors enhances periodontal regeneration. J Clin Periodontol. 1989;16:545–8.

    Article  PubMed  Google Scholar 

  179. Lioubavina-Hack N, Carmagnola D, Lynch SE, Karring T. Effect of Bio-Oss with or without platelet-derived growth factor on bone formation by “guided tissue regeneration”: a pilot study in rats. J Clin Periodontol. 2005;32:1254–60.

    Article  PubMed  Google Scholar 

  180. Nevins M, Camelo M, Nevins ML, Schenk RK, Lynch SE. Periodontal regeneration in humans using recombinant human platelet-derived growth factor-BB (rhPDGF-BB) and allogenic bone. J Periodontol. 2003;74:1282–92.

    Article  PubMed  Google Scholar 

  181. Nevins M, Giannobile WV, McGuire MK, Kao RT, Mellonig JT, Hinrichs JE, McAllister BS, Murphy KS, McClain PK, Nevins ML, Paquette DW, Han TJ, Reddy MS, Lavin PT, Genco RJ, Lynch SE. Platelet-derived growth factor stimulates bone fill and rate of attachment level gain: results of a large multicenter randomized controlled trial. J Periodontol. 2005;76:2205–15.

    Article  PubMed  Google Scholar 

  182. 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;27:109–15.

    PubMed  Google Scholar 

  183. Simion M, Rocchietta I, Kim D, Nevins M, Fiorellini J. Vertical ridge augmentation by means of deproteinized bovine bone block and recombinant human platelet-derived growth factor-BB: a histologic study in a dog model. Int J Periodontics Restorative Dent. 2006;26:415–23.

    PubMed  Google Scholar 

  184. Anitua E, Sánchez M, Orive G, Andía I. The potential impact of preparation rich in growth factors (PRGF) in different medical fields. Biomaterials. 2007;28:4551–60.

    Article  PubMed  Google Scholar 

  185. Lu HH, Vo JM, Chin HS, Lin J, Cozin M, Tsay R, Eisig S, Landesberg R. Controlled delivery of platelet-rich plasma-derived growth factors for bone formation. J Biomed Mater Res. 2008;A 15:1128–36.

    Google Scholar 

  186. Chen FM, Jin Y. Periodontal tissue engineering and regeneration: current approaches and expanding opportunities. Tissue Eng Part B Rev. 2010;16:219e55.

    Article  Google Scholar 

  187. Anitua E, Sanchez M, Orive G. Potential of endogenous regenerative technology for in situ regenerative medicine. Adv Drug Deliv Rev. 2010;62:741–52.

    Article  PubMed  Google Scholar 

  188. Chen F-M, Zhang J, Zhang M, An Y, Chen F, Wu Z-F. A review on endogenous regenerative technology in periodontal regenerative medicine. Biomaterials. 2010;31:7892–927.

    Article  PubMed  Google Scholar 

  189. Orive G, Hernández RM, Rodríguez Gascón A, Domínguez-Gil A, Pedraz JL. Drug delivery in biotechnology: present and future. Curr Opin Biotechnol. 2003;14:659–64.

    Article  PubMed  Google Scholar 

  190. Orive G, Gascón AR, Hernández RM, Domínguez-Gil A, Pedraz JL. Techniques: new approaches to the delivery of biopharmaceuticals. Trends Pharmacol Sci. 2004;25:382–7.

    Article  PubMed  Google Scholar 

  191. Kikuchi A, Okano T. Pulsatile drug release control using hydrogels. Adv Drug Deliv Rev. 2002;54:53–77.

    Article  PubMed  Google Scholar 

  192. Kohane DS, Langer R. Polymeric biomaterials in tissue engineering. Pediatr Res. 2008;63:487–91.

    Article  PubMed  Google Scholar 

  193. Schliephake H. Application of bone growth factors--the potential of different carrier systems. Oral Maxillofac Surg. 2010;14:17–22.

    Article  PubMed  Google Scholar 

  194. Chen RR, Silva EA, Yuen WW, Brock AA, Fischbach C, Lin AS, Guldberg RE, Mooney DJ. Integrated approach to designing growth factor delivery systems. FASEB J. 2007;21:3896–903.

    Article  PubMed  Google Scholar 

  195. Andreopoulos FM, Persaud I. Delivery of basic fibroblast growth factor (bFGF) from photoresponsive hydrogel scaffolds. Biomaterials. 2006;27:2468–76.

    Article  PubMed  Google Scholar 

  196. Lee M, Li W, Siu RK, Whang J, Zhang X, Soo C, Ting K, Wu BM. Biomimetic apatite-coated alginate/chitosan microparticles as osteogenic protein carriers. Biomaterials. 2009;30:6094–101.

    Article  PubMed  PubMed Central  Google Scholar 

  197. Silva EA, Mooney DJ. Spatiotemporal control of vascular endothelial growth factor delivery from injectable hydrogels enhances angiogenesis. J Thromb Haemost. 2007;5:590–8.

    Article  PubMed  Google Scholar 

  198. Kikuchi N, Kitamura C, Morotomi T, Inuyama Y, Ishimatsu H, Tabata Y, Nishihara T, Terashita M. Formation of dentin-like particles in dentin defects above exposed pulp by controlled release of fibroblast growth factor 2 from gelatin hydrogels. J Endod. 2007;33:1198–202.

    Article  PubMed  Google Scholar 

  199. Ahmed TA, Dare EV, Hincke M. Fibrin: a versatile scaffold for tissue engineering applications. Tissue Eng Part B. 2008;14:199–215.

    Article  Google Scholar 

  200. American Association of Endodontists. Endodontics-colleagues for excellence; Regenerative endodontics. 2013 Chicago, IL.

    Google Scholar 

  201. Tsesis I, Rosen E, Tamse A, Taschieri S, Del Fabbro M. Effect of guided tissue regeneration on the outcome of surgical endodontic treatment: a systematic review and meta-analysis. J Endod. 2011;37(8):1039–45.

    Article  PubMed  Google Scholar 

  202. Witherspoon DE, Small JC, Regan JD, Nunn M. Retrospective analysis of open apex teeth obturated with mineral trioxide aggregate. J Endod. 2008;34(10):1171–6.

    Article  PubMed  Google Scholar 

  203. Kontakiotis EG, Filippatos CG, Agrafioti A. Levels of evidence for the outcome of regenerative endodontic therapy. J Endod. 2014;40(8):1045–53.

    Article  PubMed  Google Scholar 

  204. Huang GT, Garcia-Godoy F. Missing concepts in De Novo Pulp regeneration. J Dent Res. 2014;93(8):717–24.

    Article  PubMed  PubMed Central  Google Scholar 

  205. Tsesis I, Rosen E, Taschieri S, Telishevsky Strauss Y, Ceresoli V, Del Fabbro M. Outcomes of surgical endodontic treatment performed by a modern technique: an updated meta-analysis of the literature. J Endod. 2013;39(3):332–9.

    Article  PubMed  Google Scholar 

  206. Tsesis I, Faivishevsky V, Kfir A, Rosen E. Outcome of surgical endodontic treatment performed by a modern technique: a meta-analysis of literature. J Endod. 2009;35(11):1505–11.

    Article  PubMed  Google Scholar 

  207. Gutmann JL, Harrison JW. Posterior endodontic surgery: anatomical considerations and clinical techniques. Int Endod J. 1985;18(1):8–34.

    Article  PubMed  Google Scholar 

  208. Kim S, Kratchman S. Modern endodontic surgery concepts and practice: a review. J Endod. 2006;32(7):601–23.

    Article  PubMed  Google Scholar 

  209. Tsesis I, Rosen E, Schwartz-Arad D, Fuss Z. Retrospective evaluation of surgical endodontic treatment: traditional versus modern technique. J Endod. 2006;32(5):412–6.

    Article  PubMed  Google Scholar 

  210. Lin L, Chen MY, Ricucci D, Rosenberg PA. Guided tissue regeneration in periapical surgery. J Endod. 2010;36(4):618–25.

    Article  PubMed  Google Scholar 

  211. Baek SH, Kim S. Bone repair of experimentally induced through-and-through defects by Gore-Tex, Guidor, and Vicryl in ferrets: a pilot study. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2001;91(6):710–4.

    Article  PubMed  Google Scholar 

  212. Maguire H, Torabinejad M, McKendry D, McMillan P, Simon JH. Effects of resorbable membrane placement and human osteogenic protein-1 on hard tissue healing after periradicular surgery in cats. J Endod. 1998;24(11):720–5.

    Article  PubMed  Google Scholar 

  213. Taschieri S, Del Fabbro M, Testori T, Saita M, Weinstein R. Efficacy of guided tissue regeneration in the management of through-and-through lesions following surgical endodontics: a preliminary study. Int J Periodontics Restorative Dent. 2008;28(3):265–71.

    PubMed  Google Scholar 

  214. Tobon SI, Arismendi JA, Marin ML, Mesa AL, Valencia JA. Comparison between a conventional technique and two bone regeneration techniques in periradicular surgery. Int Endod J. 2002;35(7):635–41.

    Article  PubMed  Google Scholar 

  215. Apaydin ES, Torabinejad M. The effect of calcium sulfate on hard-tissue healing after periradicular surgery. J Endod. 2004;30(1):17–20.

    Article  PubMed  Google Scholar 

  216. Barkhordar RA, Meyer JR. Histologic evaluation of a human periapical defect after implantation with tricalcium phosphate. Oral Surg Oral Med Oral Pathol. 1986;61(2):201–6.

    Article  PubMed  Google Scholar 

  217. Beck-Coon RJ, Newton CW, Kafrawy AH. An in vivo study of the use of a nonresorbable ceramic hydroxyapatite as an alloplastic graft material in periapical surgery. Oral Surg Oral Med Oral Pathol. 1991;71(4):483–8.

    Article  PubMed  Google Scholar 

  218. Dietrich T, Zunker P, Dietrich D, Bernimoulin JP. Periapical and periodontal healing after osseous grafting and guided tissue regeneration treatment of apicomarginal defects in periradicular surgery: results after 12 months. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2003;95(4):474–82.

    Article  PubMed  Google Scholar 

  219. Garrett K, Kerr M, Hartwell G, O’Sullivan S, Mayer P. The effect of a bioresorbable matrix barrier in endodontic surgery on the rate of periapical healing: an in vivo study. J Endod. 2002;28(7):503–6.

    Article  PubMed  Google Scholar 

  220. Marin-Botero ML, Dominguez-Mejia JS, Arismendi-Echavarria JA, Mesa-Jaramillo AL, Florez-Moreno GA, Tobon-Arroyave SI. Healing response of apicomarginal defects to two guided tissue regeneration techniques in periradicular surgery: a double-blind, randomized-clinical trial. Int Endod J. 2006;39(5):368–77.

    Article  PubMed  Google Scholar 

  221. Murashima Y, Yoshikawa G, Wadachi R, Sawada N, Suda H. Calcium sulphate as a bone substitute for various osseous defects in conjunction with apicectomy. Int Endod J. 2002;35(9):768–74.

    Article  PubMed  Google Scholar 

  222. Pecora G, De Leonardis D, Ibrahim N, Bovi M, Cornelini R. The use of calcium sulphate in the surgical treatment of a ‘through and through’ periradicular lesion. Int Endod J. 2001;34(3):189–97.

    Article  PubMed  Google Scholar 

  223. Pecora G, Kim S, Celletti R, Davarpanah M. The guided tissue regeneration principle in endodontic surgery: one-year postoperative results of large periapical lesions. Int Endod J. 1995;28(1):41–6.

    Article  PubMed  Google Scholar 

  224. Rankow HJ, Krasner PR. Endodontic applications of guided tissue regeneration in endodontic surgery. J Endod. 1996;22(1):34–43.

    Article  PubMed  Google Scholar 

  225. Sikri K, Dua SS, Kapur R. Use of tricalcium phosphate ceramic in apicoectomised teeth and in their periapical areas--clinical and radiological evaluation. J Indian Dent Assoc. 1986;58(11):442–7.

    PubMed  Google Scholar 

  226. Taschieri S, Del Fabbro M, Testori T, Weinstein R. Efficacy of xenogeneic bone grafting with guided tissue regeneration in the management of bone defects after surgical endodontics. J Oral Maxillofac Surg. 2007;65(6):1121–7.

    Article  PubMed  Google Scholar 

  227. Yoshikawa G, Murashima Y, Wadachi R, Sawada N, Suda H. Guided bone regeneration (GBR) using membranes and calcium sulphate after apicectomy: a comparative histomorphometrical study. Int Endod J. 2002;35(3):255–63.

    Article  PubMed  Google Scholar 

  228. Lindhe J. Clinical periodontology and implant dentistry. 5th ed. Oxford: Blackwell Publishing; 2008.

    Google Scholar 

  229. Bashutski JD, Wang HL. Periodontal and endodontic regeneration. J Endod. 2009;35(3):321–8.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Carlos E. Nemcovsky .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2017 Springer International Publishing Switzerland

About this chapter

Cite this chapter

Weinreb, M., Tsesis, I., Rosen, E., Taschieri, S., Del Fabbro, M., Nemcovsky, C.E. (2017). Evolving New Strategies for Periodontal, Endodontic, and Alveolar Bone Regeneration. In: Rosen, E., Nemcovsky, C., Tsesis, I. (eds) Evidence-Based Decision Making in Dentistry. Springer, Cham. https://doi.org/10.1007/978-3-319-45733-8_8

Download citation

  • DOI: https://doi.org/10.1007/978-3-319-45733-8_8

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-45731-4

  • Online ISBN: 978-3-319-45733-8

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics