Periodontal regeneration: A challenge for the tissue engineer?

Abstract Periodontitis affects around 15 per cent of human adult populations. While periodontal treatment aimed at removing the bacterial cause of the disease is generally very successful, the ability predictably to regenerate the damaged tissues remains a major unmet objective for new treatment strategies. Existing treatments include the use of space-maintaining barrier membranes (guided tissue regeneration), use of graft materials, and application of bioactive molecules to induce regeneration, but their overall effects are relatively modest and restricted in application. The periodontal ligament is rich in mesenchymal stem cells, and the understanding of the signalling molecules that may regulate their differentation has increased enormously in recent years. Applying these principles for the development of new tissue engineering strategies for periodontal regeneration will require further work to determine the efficacy of current experimental preclinical treatments, including pharmacological application of growth factors such as bone morphogenetic proteins (BMPs) or Wnts, use of autologous stem cell reimplantation strategies, and development of improved biomaterial scaffolds. This article describes the background to this problem, addresses the current status of periodontal regeneration, including the background biology, and discusses the potential for some of these experimental therapies to achieve the goal of clinically predictable periodontal regeneration.

[1]  C. Rubini,et al.  Comparative study of DFDBA in combination with enamel matrix derivative versus DFDBA alone for treatment of periodontal intrabony defects at 12 months post-surgery , 2011, Clinical Oral Investigations.

[2]  D. Dickinson,et al.  Growth/differentiation factor-5: a candidate therapeutic agent for periodontal regeneration? A review of pre-clinical data. , 2010, Journal of clinical periodontology.

[3]  A. Sculean,et al.  Clinical and histologic evaluation of granular Beta-tricalcium phosphate for the treatment of human intrabony periodontal defects: a report on five cases. , 2010, Journal of periodontology.

[4]  S. Rawlinson,et al.  Adult Rat Bones Maintain Distinct Regionalized Expression of Markers Associated with Their Development , 2009, PloS one.

[5]  M. Al-Masri,et al.  Absorption and release of protein from hydroxyapatite-polylactic acid (HA-PLA) membranes. , 2009, Journal of dentistry.

[6]  P. Coulthard,et al.  Enamel matrix derivative (Emdogain(R)) for periodontal tissue regeneration in intrabony defects. , 2009, The Cochrane database of systematic reviews.

[7]  S. Gronthos,et al.  Stem cells and future periodontal regeneration. , 2009, Periodontology 2000.

[8]  R. Druzinsky,et al.  Neural Crest Lineage Segregation: a Blueprint for Periodontal Regeneration , 2009, Journal of dental research.

[9]  S. Pippig,et al.  Periodontal wound healing/regeneration following implantation of recombinant human growth/differentiation factor-5 (rhGDF-5) in an absorbable collagen sponge carrier into one-wall intrabony defects in dogs: a dose-range study. , 2009, Journal of clinical periodontology.

[10]  P. Gong,et al.  Research on promoting periodontal regeneration with human basic fibroblast growth factor-modified bone marrow mesenchymal stromal cell gene therapy. , 2009, Cytotherapy.

[11]  Andreas Schuetz,et al.  Development of an injectable composite as a carrier for growth factor-enhanced periodontal regeneration. , 2008, Journal of clinical periodontology.

[12]  F. Schwarz,et al.  Clinical and histologic evaluation of an enamel matrix derivative combined with a biphasic calcium phosphate for the treatment of human intrabony periodontal defects. , 2008, Journal of periodontology.

[13]  S. Girod,et al.  Embryonic origin and Hox status determine progenitor cell fate during adult bone regeneration , 2008, Development.

[14]  D. Bosshardt Biological mediators and periodontal regeneration: a review of enamel matrix proteins at the cellular and molecular levels. , 2008, Journal of clinical periodontology.

[15]  L. Trombelli,et al.  Clinical outcomes with bioactive agents alone or in combination with grafting or guided tissue regeneration. , 2008, Journal of clinical periodontology.

[16]  L. Jeng,et al.  Periodontal regeneration using ex vivo autologous stem cells engineered to express the BMP-2 gene: an alternative to alveolaplasty , 2008, Gene Therapy.

[17]  Ying Zheng,et al.  Periodontal Ligament Stem Cell‐Mediated Treatment for Periodontitis in Miniature Swine , 2008, Stem cells.

[18]  B. Rai,et al.  Biomarkers of periodontitis in oral fluids. , 2008, Journal of oral science.

[19]  Chen Zhao,et al.  Alveolar bone regeneration of subcutaneously transplanted rat molar. , 2008, Bone.

[20]  R. Nusse,et al.  Bone Regeneration Is Regulated by Wnt Signaling , 2007, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[21]  A. Sculean,et al.  Effect of platelet-rich plasma on the healing of intrabony defects treated with an enamel matrix protein derivative and a natural bone mineral. , 2007, Journal of clinical periodontology.

[22]  Xu Cao,et al.  Multiplicity of BMP Signaling in Skeletal Development , 2007, Annals of the New York Academy of Sciences.

[23]  Seong-Ho Choi,et al.  Evidence for expansion-based temporal BMP4/NOGGIN interactions in specifying periodontium morphogenesis , 2007, Cell and Tissue Research.

[24]  H. Arzate,et al.  Human dental follicle cells acquire cementoblast features under stimulation by BMP-2/-7 and enamel matrix derivatives (EMD) in vitro , 2007, Cell and Tissue Research.

[25]  B. McAllister,et al.  Bone augmentation techniques. , 2007, Journal of periodontology.

[26]  G. Belibasakis,et al.  Effects of growth factors and cytokines on osteoblast differentiation. , 2006, Periodontology 2000.

[27]  P. Leboy,et al.  Regulating Bone Growth and Development with Bone Morphogenetic Proteins , 2006, Annals of the New York Academy of Sciences.

[28]  Kozo Nakamura,et al.  Effect of GDF‐5 on ligament healing , 2006, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[29]  William V Giannobile,et al.  Platelet-derived growth factor stimulates bone fill and rate of attachment level gain: results of a large multicenter randomized controlled trial. , 2005, Journal of periodontology.

[30]  U. Ripamonti,et al.  Bone morphogenetic proteins in craniofacial and periodontal tissue engineering: experimental studies in the non-human primate Papio ursinus. , 2005, Cytokine & growth factor reviews.

[31]  J. Westendorf,et al.  Wnt signaling in osteoblasts and bone diseases. , 2004, Gene.

[32]  T. Karring,et al.  GTR treatment of intrabony defects with PLA/PGA copolymer or collagen bioresorbable membranes in combination with deproteinized bovine bone (Bio-Oss) , 2004, Clinical Oral Investigations.

[33]  Stan Gronthos,et al.  Investigation of multipotent postnatal stem cells from human periodontal ligament , 2004, The Lancet.

[34]  M. Tonetti,et al.  Long-term tooth survival following regenerative treatment of intrabony defects. , 2004, Journal of periodontology.

[35]  William V Giannobile,et al.  Engineering of tooth-supporting structures by delivery of PDGF gene therapy vectors. , 2004, Molecular therapy : the journal of the American Society of Gene Therapy.

[36]  M. Somerman,et al.  Growth and amelogenin-like factors in periodontal wound healing. A systematic review. , 2003, Annals of periodontology.

[37]  J. Gunsolley,et al.  The efficacy of bone replacement grafts in the treatment of periodontal osseous defects. A systematic review. , 2003, Annals of periodontology.

[38]  S. Lynch,et al.  Periodontal regeneration in humans using recombinant human platelet-derived growth factor-BB (rhPDGF-BB) and allogenic bone. , 2003, Journal of periodontology.

[39]  H. Shiba,et al.  Differential gene expression of bone‐related proteins in epithelial and fibroblastic cells derived from human periodontal ligament , 2003, Cell biology international.

[40]  R. Rutherford,et al.  Gene therapy of bone morphogenetic protein for periodontal tissue engineering. , 2003, Journal of periodontology.

[41]  J. Papkoff,et al.  Activated β-catenin induces osteoblast differentiation of C3H10T1/2 cells and participates in BMP2 mediated signal transduction , 2003 .

[42]  Y. Shimabukuro,et al.  Periodontal Regeneration by FGF-2 (bFGF) in Primate Models , 2001, Journal of dental research.

[43]  S. Ivanovski,et al.  Expression of bone associated macromolecules by gingival and periodontal ligament fibroblasts. , 2001, Journal of periodontal research.

[44]  R. Talwar,et al.  Effects of carrier release kinetics on bone morphogenetic protein-2-induced periodontal regeneration in vivo. , 2001, Journal of clinical periodontology.

[45]  R. Yukna,et al.  Multi-center clinical comparison of combination anorganic bovine-derived hydroxyapatite matrix (ABM)/cell binding peptide (P-15) and ABM in human periodontal osseous defects. 6-month results. , 2000, Journal of periodontology.

[46]  C. Kirker-Head,et al.  Potential applications and delivery strategies for bone morphogenetic proteins. , 2000, Advanced drug delivery reviews.

[47]  M. Parkar,et al.  Retroviral transduction of human periodontal cells with a temperature-sensitive SV40 large T antigen. , 1999, Archives of oral biology.

[48]  F. Hughes,et al.  Effects of occlusal loading on ankylosis, bone, and cementum formation during bone morphogenetic protein-2-stimulated periodontal regeneration in vivo. , 1999, Journal of periodontology.

[49]  T. Nishihara,et al.  Recombinant Human Bone Morphogenetic Protein-2 Stimulates Osteoblastic Differentiation in Cells Isolated from Human Periodontal Ligament , 1999, Journal of dental research.

[50]  D. Cochran,et al.  Clinical evaluation of Bio-Oss: a bovine-derived xenograft for the treatment of periodontal osseous defects in humans. , 1999, Journal of clinical periodontology.

[51]  Harris Rj Treatment of furcation defects with DFDBA combined with GTR: human histologic evaluation of a case. , 1999 .

[52]  M. Sanz,et al.  Treatment of deep and shallow intrabony defects. A multicenter randomized controlled clinical trial. , 1998, Journal of clinical periodontology.

[53]  R. Yukna,et al.  Bone replacement grafts. The bone substitutes. , 1998, Dental clinics of North America.

[54]  R. Yukna,et al.  BONE REPLACEMENT GRAFTS , 1998, Dental Clinics of North America.

[55]  S. Lee,et al.  Controlled release of platelet-derived growth factor from porous poly(L-lactide) membranes for guided tissue regeneration. , 1998, Journal of controlled release : official journal of the Controlled Release Society.

[56]  J. Wozney,et al.  Recombinant Human Bone Morphogenetic Protein-2 Promotes Wound Healing in Rat Periodontal Fenestration Defects , 1997, Journal of dental research.

[57]  D. Graves,et al.  Cells with osteoblastic phenotypes can be explanted from human gingiva and periodontal ligament. , 1997, Journal of periodontology.

[58]  J. Wozney,et al.  Periodontal repair in dogs: evaluation of rhBMP-2 carriers. , 1996, The International journal of periodontics & restorative dentistry.

[59]  M. Tonetti,et al.  Factors affecting the healing response of intrabony defects following guided tissue regeneration and access flap surgery. , 1996, Journal of clinical periodontology.

[60]  M. Tonetti,et al.  Periodontal regeneration of human intrabony defects with bioresorbable membranes. A controlled clinical trial. , 1996, Journal of periodontology.

[61]  M. Reynolds,et al.  Fate of demineralized freeze-dried bone allografts in human intrabony defects. , 1996, Journal of periodontology.

[62]  F. Hughes,et al.  The effects of bone morphogenetic protein-2, -4, and -6 on differentiation of rat osteoblast cells in vitro. , 1995, Endocrinology.

[63]  J. Wozney,et al.  Periodontal repair in dogs: recombinant human bone morphogenetic protein-2 significantly enhances periodontal regeneration. , 1995, Journal of periodontology.

[64]  A. Reddi,et al.  Bone morphogenetic proteins induce periodontal regeneration in the baboon (Papio ursinus) , 1994, Journal of periodontal research.

[65]  P. Wesselink,et al.  Repair processes in the periodontium following dentoalveolar ankylosis: the effect of masticatory function. , 1994, Journal of clinical periodontology.

[66]  R. Rutherford,et al.  Platelet-derived growth factor and dexamethasone combined with a collagen matrix induce regeneration of the periodontium in monkeys. , 1993, Journal of clinical periodontology.

[67]  E. Amento,et al.  Bone morphogenetic protein‐2b stimulation of growth and osteogenic phenotypes in rat osteoblast‐like cells: Comparison with TGF‐β1 , 1991 .

[68]  M. Somerman,et al.  Human periodontal cells initiate mineral-like nodules in vitro. , 1991, Journal of periodontology.

[69]  M S Reddy,et al.  The effects of short-term application of a combination of platelet-derived and insulin-like growth factors on periodontal wound healing. , 1991, Journal of periodontology.

[70]  V. Rosen,et al.  Recombinant human bone morphogenetic protein induces bone formation. , 1990, Proceedings of the National Academy of Sciences of the United States of America.

[71]  B Lowenberg,et al.  Paravascular cells in endosteal spaces of alveolar bone contribute to periodontal ligament cell populations , 1987, The Anatomical record.

[72]  J. Wennström,et al.  New attachment formation in the human periodontium by guided tissue regeneration. Case reports. , 1986, Journal of clinical periodontology.

[73]  T. Karring,et al.  New attachment formation as the result of controlled tissue regeneration. , 1984, Journal of clinical periodontology.

[74]  M. Urist Bone: Formation by Autoinduction , 1965, Science.

[75]  J. Papkoff,et al.  Activated beta-catenin induces osteoblast differentiation of C3H10T1/2 cells and participates in BMP2 mediated signal transduction. , 2003, Biochemical and biophysical research communications.

[76]  P. Adriaens,et al.  Abstracts , 1999, British Dental Journal.

[77]  M. Heliotis,et al.  Induction of cementogenesis by recombinant human osteogenic protein-1 (hop-1/bmp-7) in the baboon (Papio ursinus). , 1996, Archives of oral biology.

[78]  E. Wang,et al.  Bone morphogenetic protein-2 causes commitment and differentiation in C3H10T1/2 and 3T3 cells. , 1993, Growth factors.

[79]  A. Economides,et al.  0163-769X/03/$20.00/0 Endocrine Reviews 24(2):218–235 Printed in U.S.A. Copyright © 2003 by The Endocrine Society doi: 10.1210/er.2002-0023 Bone Morphogenetic Proteins, Their Antagonists, and the Skeleton , 2022 .