|Year : 2018 | Volume
| Issue : 4 | Page : 168-173
Regenerative periodontics in restoring oral functions: A power to regenerate what's lost
Hunny Sharma1, Swati Verma2
1 Department of Public Health Dentistry, Triveni Institute of Dental Sciences, Hospital and Research Centre, Bilaspur, Chhattisgarh, India
2 Department of Public Health Dentistry, Rungta College of Dental Sciences and Research, Bhilai, Chhattisgarh, India
|Date of Web Publication||18-Dec-2018|
MD 264, Phase 4, Near AIIMS Residential Complex, Kabir Nagar, Tatibandh, Raipur - 492 099, Chhattisgarh
Although human oral cavity benefits from remarkable mechanical and functional properties, still it faces continuous insult and damage resulting from exposure to microbial attacks. In the past where conventional dentistry was only focused on evaluating, restoration, and replacement of the diseased oral structures. The recent era of advancement in the field of materials science, molecular biology, tissue engineering, and stem cell research's had let to the path of development of new era of periodontal engineering known as regenerative periodontics. The ultimate goal of regenerative periodontics is the regeneration of the lost periodontium due to advanced periodontal disease. Currently, scientists are working on a wide range of biomaterials and scaffolds, genes, stem cells, and growth factors in the hope of achieving more predictable outcomes in regenerative periodontics. Future research areas in regenerative periodontics include three-dimensional printing, tissue engineering, and gene therapy strategies which give more positive and predictable outcomes of regenerative periodontics. This review provides an overview of current on-going technique and researches in the field of regenerative periodontics and also will show a glimpse of what the future holds.
Keywords: Guided tissue regeneration, oral health, periodontal, periodontics, regeneration, stem cells
|How to cite this article:|
Sharma H, Verma S. Regenerative periodontics in restoring oral functions: A power to regenerate what's lost. SRM J Res Dent Sci 2018;9:168-73
|How to cite this URL:|
Sharma H, Verma S. Regenerative periodontics in restoring oral functions: A power to regenerate what's lost. SRM J Res Dent Sci [serial online] 2018 [cited 2020 Oct 1];9:168-73. Available from: http://www.srmjrds.in/text.asp?2018/9/4/168/247839
| Introduction|| |
Plaque-associated oral diseases are among the major public health problems with dental caries, gingival and periodontal diseases being major contributors to tooth loss., Periodontitis imparts both soft-tissue and hard-tissue destruction in the supporting tissues of the teeth exhibiting itself by destroying alveolar bone, periodontal ligament, and gingiva ultimately resulting in contamination of root cementum following exposure to the oral fluids and bacteria., Periodontics is not only the science of oral hygiene maintenance and controlling inflammatory aspect of the gingival and periodontal disease, but it also aims to regenerate the destroyed periodontal tissues.
Regenerative periodontics is one such aspect of the field of periodontia which deals with regeneration of destroyed periodontal tissues. This technique basically comprises several sub-techniques which are especially designed for restoration and functional adaptation of tooth-supporting structures lost as a result of severe periodontitis or gingival trauma. In simpler terms, the ultimate goal of these techniques is the restoration and functional adaptation of supporting structures of the tooth by techniques that promote the formation of the new periodontal ligament with its fibers well inserted into adjacent newly-formed cementum and alveolar bone.
A periodontal graft material is said to be ideal when it is safe, nonallergenic, nontoxic, biocompatible and with no risk of disease transmission. Another characteristic which are required for a good graft material is its strength to maintain space and appropriate rate of degradation in the oral environment. Periodontal regeneration techniques evolved during recent past includes soft-tissue grafts, bone replacement grafts, root surface biomodification techniques, guided tissue or bone regeneration, and delivery target-specific growth factors or gene therapy techniques. These new techniques and biomaterials offers interesting potential alternatives to conventional periodontal treatments for the repair and regeneration of the effected periodontal tissue by series of complex events involving recruitment of locally-derived progenitor cells which eventually differentiate into periodontal ligament cells, cementoblasts, or osteoblasts.
In this review we have tried to focus on biomaterials and techniques of periodontal regeneration developed during the last decades and provide a glimpse of most recent findings and future avenues.
| Regenerative Periodontics in Alveolar Bone Defects|| |
Outcome prediction of regenerative periodontics mainly depends on the morphology of the alveolar infra-bony defect. Moreover, one such classification of alveolar infra bony defect was proposed by Goldman and Cohen in 1958 depending on a number of osseous walls surrounding the defect, which may be either one wall, two wall, or three wall, respectively. A common approach in the repair of these defects is periodontal flap approach coupled with the placement of bone grafts or implant materials into the curetted and properly debrided bony defects with the hope of periodontal regeneration.
| Factors Predicting Outcome of Regenerative Periodontics in Alveolar Bone Defects|| |
Morphology of the alveolar infra-bony defect being the most important factor in outcome prediction of regenerative periodontics like alveolar infra-bony defects of depth defects 3 mm or more intraosseous depth and angle of <25° show the more promising outcome as compared to shallow defects.,,,
The other factors which also play a crucial role are:
- Removal of toxins from periodontal disease effected root using bio-modification.
- Provision of space which allows adequate coronal migration of pluripotent cells derived from the intact periodontal ligament on the root surface using specialized membranes and adequate harvested bone substitutes.
- Wound stabilization using optimal flap design and adequate suturing techniques to protect the blood coagulum for un-interrupted healing.
- Primary wound healing by well-adapted flap design and specialized suturing for complete wound closure.
In addition to above-mentioned factors several host-related factors also play an important role in the outcome of regenerative periodontics such as deleterious habits (smoked and smokeless tobacco use), oral hygiene maintenance, and systemic diseases.,
| Hard Tissue Grafts Used to Treat Alveolar Bone Defects by Regenerative Periodontics|| |
There are some hard tissue grafts, which had been tested for periodontal tissue regeneration as listed.,
These are the grafts, which are harvested from one location and transferred to other location within the same organism, for example, cancellous and/or cortical and extra oral/intra oral.
These are the grafts, which are harvested from one organism but are transferred and invested into another organism of the same species, for example, fresh and/or frozen bone, freeze-dried bone allograft (FDBA), and demineralized FDBA (DFDBA) [Table 1].
|Table 1: Some commercially available allograft materials used in regenerative periodontics|
Click here to view
These are the grafts, which are harvested and transferred between organisms of a different species, for example, bovine hydroxy-apatite, porcine bone, equine bone, and coralline calcium carbonate [Table 2].
|Table 2: Some commercially available xenograft materials used in regenerative periodontics|
Click here to view
These are synthetic or inorganic substitute used as implant material which can be used for repair of alveolar defects similar to as that of previously mentioned graft material, for example, bioactive glasses, calcium phosphates (hydroxyapatite, tricalcium phosphate and other calcium phosphates (brushite, monetite, and calcium polyphosphates), and calcium sulfate [Table 3].
|Table 3: Some commercially available alloplast materials used in regenerative periodontics|
Click here to view
The rationale behind the use of these hard tissue grafts, i.e. autogenous, allogenic, xenogenic, and alloplastic graft material is the assumption that these graft materials will serve as an osteoconductive scaffold for bone formation resulting in the formation of bone-forming cells (osteogenesis) and bone inductive substances (osteoinduction). However, several studies conducted so far had demonstrated that periodontal repair by hard-tissue graft is by the formation of long junctional epithelium rather than desired new connective tissue attachment.
| Bio-Modification of the Tooth Root Surface in Regenerative Periodontics|| |
Although it was assumed that biomodification of the periodontitis-involved root surface with citric acid would help to attain adequate formation of a new connective tissue attachment, the outcome of controlled clinical trials lacked promising results in clinical outcomes as compared to nontreated controls.,
Recent understanding and advancement of various biological models had let to use of bio-modification of the root surface with enamel matrix proteins during periodontal surgery followed by demineralization using ethylenediaminetetraacetic acid has to promote periodontal regeneration, resulting in initiation of events that occur only at the time of growth of periodontal tissues., One of the recent advances is a product known as Emdogain® which is a purified acid extract of porcine origin contains enamel matrix derivatives (EMDs).
| Guided Tissue Regeneration in Regenerative Periodontics|| |
Recent histological studies reveal that a new connective tissue attachment can only be obtained satisfactorily when the obtained cells from periodontal ligament had an adequate chance and time to settle on the bio modified root surface during the healing phase. To achieve this, a physical barrier membrane should be placed on previously periodontitis-affected tooth root surface which is targeted to be repopulated with cells from the periodontal ligament to achieve new connective tissue attachment. Guided tissue regeneration serves as one such way to place the physical barrier for the treatment of localized gingival recessions and various periodontal defects such as infra-bony defects and furcation involvements.,,,
Various types of barrier membranes in regard to composition, configuration, and design had been evaluated to achieve such satisfactory results. One such barrier membrane is a nonresorbable membrane composed of expanded polytetrafluoroethylene which had been successfully tested in both animal and human trials. However in recent years, natural or synthetic bioabsorbable barrier membranes had been given more importance over the nonresorbable membranes to avoid the need for membrane removal in a follow-up surgery, for example, barrier membranes made up of polylactic acid or copolymers of polylactic acid and polyglycolic acid. Use of these guided tissue regeneration techniques had made great breakthroughs in the treatment of gingival and periodontal defects by increased attachment gain, reduction of probing depth, less gingival recession, and more gain in hard tissue probing at surgical re-entry.
| Gene Therapeutics in Regenerative Periodontics|| |
Researches in the field of genetics have been carried out for decades with the dream of transferring or manipulating genes for clinical applications and promising preclinical outcomes in curing hereditary and nonhereditary diseases. Gene therapy aims to transfer the manipulated functional genes to replace abnormal and malfunctioning genes utilizing a viral or nonviral vector as a carrier molecule.,
Gene vectors can either be directly introduced to the target site called in vivo technique or the selected cells can be harvested, expanded, genetically transduced, and then re-implanted the desired site as in ex vivo technique. In vivo technique usually based on gene delivery system using physical means such as tissue injection, biolistics, or systemic infusion of cell-specific receptor-mediated DNA carriers like reconstructed liposome's or viruses. While ex vivo techniques usually involve fibroblasts and hematopoietic stem cells, which are harvested, genetically modified and then re-implanted to the desired site. Recent clinical trials using PDGF-gene transfer strategies have been performed using plasmid, and Ad/PDGF gene deliver for regeneration of periodontal tissue.
| Emerging Techniques in Regenerative Periodontics|| |
Systemic anabolic agents
Teriparatide a commercially available form of parathyroid hormone (PTH) had shown to be promising anabolic agent. Teriparatide is basically used as self-administered daily subcutaneous injections to the thigh or abdomen and consist of 34 amino acids of the PTH molecule.
The anabolic effect of teriparatide mainly relies on low, intermittent doses which result in increased proliferation of preosteoblasts and indirectly decreasing the osteoblast apoptosis. This results in bone formation.
Local delivery of growth factors
One of the other recent trends is controlled and target specific local delivery of growth factors, for example, fibroblast growth factor (FGF-2). The recombinant human FGF-2 mainly exhibits mitogenic and angiogenic actions when it binds to heparin. This results in the differentiation of osteoprogenitor cells, resulting in increased bone formation.,,
Several studies utilizing cell therapy had also expressed itself as a valuable therapeutic option in regenerative periodontics. Use of this technique relies on potential factors like ease of harvesting the cells to be seeded into periodontal defects, nonimmunogenic properties, highly proliferative nature and should exhibit an extraordinary ability to differentiate into the various types of cells with the ability to repair and reproduce damaged periodontal structures. In search of such potential cells, which can serve all the desired properties, adult mesenchymal stem cells had been looked on as potentially one having the ability to differentiate into osteoblasts, fibroblasts, and cementoblasts.,
Three-dimensional bioprinting and microscale technologies in regenerative periodontics
Recent advances in tissue engineering approach particular three-dimensional (3D) printing technologies where synthetic extracellular matrix environment had played a major breakthrough in the reconstruction of complex periodontal tissue and adjoining tissue structures. 3D printed biomaterials served as promising tools giving the advantage of custom fabrication of tissue scaffold in regard to size, configuration, and architecture of the targeted defect and had showed and extraordinary efficacy in the regeneration of new complex structures periodontal ligaments which serve as good as natural.,,
Platelet-rich fibrin with 1.2% rosuvastatin
Choukroun's platelet-rich fibrin (PRF), a second-generation platelet concentrate known for both soft- and hard-tissue healing consists of a fibrin network (slow polymerizing) enmeshing cytokines, glycoproteins, and glycanic chains while rosuvastatin (RSV) is an important class of bone-modulating agents which are basically hydroxymethylglutaryl coenzyme A reductase inhibitor drugs are well known for their anti-inflammatory and antioxidant properties. Use of PRF along with 1.2% RSV gel had shown to result in significantly greater clinical attachment level gain and also had shown to reduce probing depth and infra-bony defect depth over as compared to the use of PRF alone.,,,
Enamel matrix derivative
Various animal and human studies have shown EMD as an effective agent to stimulate periodontal regeneration and as an adjunct in reconstituting the lost periodontal structures, i.e. root cementum, periodontal ligament, and alveolar bone.,,, EMD had proved to be superior as compared to open flap debridement alone for probing pocket depth reduction, clinical attachment gain, and radiographic bone fill., Researches over a decade had shown that the combination of EMD and bovine-derived xenograft might enhance clinical attachment gain compared to EMD alone. Thus making it the most potential agent to be used in regenerative periodontics. Still, researches are ongoing to tackle the viscous nature of EMD which not be able to prevent a collapse of the soft tissue into wide intrabony defects. Several attempts are being carried out to combine EMD with different materials to tackle this problem and further enhance the regenerative outcomes (e.g. membranes or bone grafts).
| Conclusions|| |
In the past, the main aim of the dentistry was limited to restoring the decayed tooth tissue and maintaining oral hygiene. The focus has been greatly expanded in recent years due to research in regenerative dentistry, to include functional restoration of oral structures. One such great expansion in the field of periodontics is regenerative periodontics. Continuous and ongoing challenges in clinical setup for the treatment of various gingival and periodontal defects had continued to stimulate important research and clinical development in the field of regenerative periodontics, which in turn will shape the future concept of regenerative defects. Most of the regenerative technique elaborated in this review had created a breakthrough in regenerative periodontics however many are still in under development stage and not currently available due to practice difficulty in implementation. However, these emerging technologies, such as stem cell therapy, local delivery of growth factors, and bone anabolic agents, gene therapy, and newer agents in biomodification of the periodontally compromised teeth offer newer opportunities to enhance the predictability of current regenerative periodontic techniques and inspire the development of more advanced and bio-friendly treatment strategies. Till date, the regeneration or reconstruction of small-to-moderate size periodontal soft-tissue and bone defects had been achieved using engineered cell-scaffold constructs which require immense collaborative efforts of periodontists, cellular biologists, geneticists, and biomedical engineers. However, the predictable reconstruction of the normal structure and functionality of a tooth-supporting apparatus remains challenging. Hence, the future of regenerative periodontics depends on experts in periodontics working together with cellular biologists, geneticists, biomedical engineers, and materials scientists that strive to find and perfect novel approaches and techniques to address the issues above.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
The pathogenesis of periodontal diseases. J Periodontol 1999;70:457-70.
The American Academy of Periodontology. Diagnosis of Periodontal Diseases position paper. Chicago: The American Academy of Periodontology; 1995.
Cekici A, Kantarci A, Hasturk H, Van Dyke TE. Inflammatory and immune pathways in the pathogenesis of periodontal disease. Periodontol 2000 2014;64:57-80.
Listgarten MA. Pathogenesis of periodontitis. J Clin Periodontol 1986;13:418-30.
Choi SH. A new role for periodontists in the 21st
century. J Periodontal Implant Sci 2011;41:261-2.
Wang HL, Greenwell H, Fiorellini J, Giannobile W, Offenbacher S, Salkin L, et al.
Periodontal regeneration. J Periodontol 2005;76:1601-22.
Hughes FJ, Ghuman M, Talal A. Periodontal regeneration: A challenge for the tissue engineer? Proc Inst Mech Eng H 2010;224:1345-58.
Darby I. Periodontal materials. Aust Dent J 2011;56 Suppl 1:107-18.
Young MP, Carter DH, Worthington H, Korachi M, Drucker DB. Microbial analysis of bone collected during implant surgery: A clinical and laboratory study. Clin Oral Implants Res 2001;12:95-103.
Bartold PM, Narayanan AS, editors. Periodontal regeneration. In: Biology of the Periodontal Connective Tissues. Chicago: Quintessence Publishing; 1998. p. 60-73.
Goldman H, Cohen W. The infrabony pocket: Classificassion and treatment. J Periodontol 1958;29:272-91.
Ramseier CA, Rasperini G, Batia S, Giannobile WV. Advanced reconstructive technologies for periodontal tissue repair. Periodontol 2000 2012;59:185-202.
Eickholz P, Hörr T, Klein F, Hassfeld S, Kim TS. Radiographic parameters for prognosis of periodontal healing of infrabony defects: Two different definitions of defect depth. J Periodontol 2004;75:399-407.
Tonetti MS, Pini-Prato G, Cortellini P. Periodontal regeneration of human intrabony defects. IV. Determinants of healing response. J Periodontol 1993;64:934-40.
Klein F, Kim TS, Hassfeld S, Staehle HJ, Reitmeir P, Holle R, et al.
Radiographic defect depth and width for prognosis and description of periodontal healing of infrabony defects. J Periodontol 2001;72:1639-46.
Tsitoura E, Tucker R, Suvan J, Laurell L, Cortellini P, Tonetti M, et al.
Baseline radiographic defect angle of the intrabony defect as a prognostic indicator in regenerative periodontal surgery with enamel matrix derivative. J Clin Periodontol 2004;31:643-7.
Cortellini P, Paolo G, Prato P, Tonetti MS. Long-term stability of clinical attachment following guided tissue regeneration and conventional therapy. J Clin Periodontol 1996;23:106-11.
Cortellini P, Pini-Prato G, Tonetti M. Periodontal regeneration of human infrabony defects (V). Effect of oral hygiene on long-term stability. J Clin Periodontol 1994;21:606-10.
Sheikh Z, Hamdan N, Ikeda Y, Grynpas M, Ganss B, Glogauer M, et al.
Natural graft tissues and synthetic biomaterials for periodontal and alveolar bone reconstructive applications: A review. Biomater Res 2017;21:9.
Caton J, Zander HA. Osseous repair of an infrabony pocket without new attachment of connective tissue. J Clin Periodontol 1976;3:54-8.
Listgarten MA, Rosenberg MM. Histological study of repair following new attachment procedures in human periodontal lesions. J Periodontol 1979;50:333-44.
Moore JA, Ashley FP, Waterman CA. The effect on healing of the application of citric acid during replaced flap surgery. J Clin Periodontol 1987;14:130-5.
Fuentes P, Garrett S, Nilvéus R, Egelberg J. Treatment of periodontal furcation defects. Coronally positioned flap with or without citric acid root conditioning in class II defects. J Clin Periodontol 1993;20:425-30.
Hammarström L. Enamel matrix, cementum development and regeneration. J Clin Periodontol 1997;24:658-68.
Gestrelius S, Lyngstadaas SP, Hammarström L. Emdogain – Periodontal regeneration based on biomimicry. Clin Oral Investig 2000;4:120-5.
Jaiswal GR, Kumar R, Khatri PM, Jaiswal SG, Bhongade ML. The effectiveness of enamel matrix protein (Emdogain(®)) in combination with coronally advanced flap in the treatment of multiple marginal tissue recession: A clinical study. J Indian Soc Periodontol 2012;16:224-30.
] [Full text]
Pini Prato G, Clauser C, Cortellini P, Tinti C, Vincenzi G, Pagliaro U, et al.
Guided tissue regeneration versus mucogingival surgery in the treatment of human buccal recessions. A 4-year follow-up study. J Periodontol 1996;67:1216-23.
Cortellini P, Bowers GM. Periodontal regeneration of intrabony defects: An evidence-based treatment approach. Int J Periodontics Restorative Dent 1995;15:128-45.
Karring T, Cortellini P. Regenerative therapy: Furcation defects. Periodontol 2000 1999;19:115-37.
Machtei EE, Schallhorn RG. Successful regeneration of mandibular class II furcation defects: An evidence-based treatment approach. Int J Periodontics Restorative Dent 1995;15:146-67.
Needleman IG, Worthington HV, Giedrys-Leeper E, Tucker RJ. Guided tissue regeneration for periodontal infra-bony defects. Cochrane Database Syst Rev 2006;2:CD001724.
Gupta K, Singh S, Garg KN. Gene therapy in dentistry: Tool of genetic engineering. Revisited. Arch Oral Biol 2015;60:439-46.
Friedmann T, Roblin R. Gene therapy for human genetic disease? Science 1972;175:949-55.
Chatterjee A, Singh N, Saluja M. Gene therapy in periodontics. J Indian Soc Periodontol 2013;17:156-61.
] [Full text]
Bashutski JD, Eber RM, Kinney JS, Benavides E, Maitra S, Braun TM, et al.
Teriparatide and osseous regeneration in the oral cavity. N Engl J Med 2010;363:2396-405.
Kitamura M, Akamatsu M, Machigashira M, Hara Y, Sakagami R, Hirofuji T, et al.
FGF-2 stimulates periodontal regeneration: Results of a multi-center randomized clinical trial. J Dent Res 2011;90:35-40.
Ninomiya M, Azuma T, Kido J, Murakami S, Nagata T. Successful case of periodontal tissue repair with fibroblast growth factor-2: Long-term follow-up and comparison to enamel matrix derivative. Clin Adv Periodontics 2013;3:215-21.
Kitamura M, Nakashima K, Kowashi Y, Fujii T, Shimauchi H, Sasano T, et al.
Periodontal tissue regeneration using fibroblast growth factor-2: Randomized controlled phase II clinical trial. PLoS One 2008;3:e2611.
Gonshor A, McAllister BS, Wallace SS, Prasad H. Histologic and histomorphometric evaluation of an allograft stem cell-based matrix sinus augmentation procedure. Int J Oral Maxillofac Implants 2011;26:123-31.
McAllister BS. Stem cell-containing allograft matrix enhances periodontal regeneration: Case presentations. Int J Periodontics Restorative Dent 2011;31:149-55.
Tevlin R, McArdle A, Atashroo D, Walmsley GG, Senarath-Yapa K, Zielins ER, et al.
Biomaterials for craniofacial bone engineering. J Dent Res 2014;93:1187-95.
Park CH, Rios HF, Taut AD, Padial-Molina M, Flanagan CL, Pilipchuk SP, et al.
Image-based, fiber guiding scaffolds: A platform for regenerating tissue interfaces. Tissue Eng Part C Methods 2014;20:533-42.
Rasperini G, Pilipchuk SP, Flanagan CL, Park CH, Pagni G, Hollister SJ, et al
. 3D-printed bioresorbable scaffold for periodontal repair. J Dent Res 2015;94:153S-7S.
Dohan DM, Choukroun J, Diss A, Dohan SL, Dohan AJ, Mouhyi J, 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:e37-44.
Dohan DM, Choukroun J, Diss A, Dohan SL, Dohan AJ, Mouhyi J, et al.
Platelet-rich fibrin (PRF): A second-generation platelet concentrate. Part III: Leucocyte activation: A new feature for platelet concentrates? Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2006;101:e51-5.
LaRosa JC, Grundy SM, Kastelein JJ, Kostis JB, Greten H, Treating to New Targets (TNT) Steering Committee and Investigators, et al.
Safety and efficacy of atorvastatin-induced very low-density lipoprotein cholesterol levels in patients with coronary heart disease (a post hoc
analysis of the treating to new targets [TNT] study). Am J Cardiol 2007;100:747-52.
Pradeep AR, Garg V, Kanoriya D, Singhal S. Platelet-rich fibrin with 1.2% rosuvastatin for treatment of intrabony defects in chronic periodontitis: A randomized controlled clinical trial. J Periodontol 2016;87:1468-73.
Hammarström 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.
Sculean A, Donos N, Brecx M, Reich E, Karring T. Treatment of intrabony defects with guided tissue regeneration and enamel-matrix-proteins. An experimental study in monkeys. J Clin Periodontol 2000;27:466-72.
Sculean A, Donos N, Windisch P, Brecx M, Gera I, Reich E, et al.
Healing of human intrabony defects following treatment with enamel matrix proteins or guided tissue regeneration. J Periodontal Res 1999;34:310-22.
Sculean A, Chiantella GC, Windisch P, Donos N. Clinical and histologic evaluation of human intrabony defects treated with an enamel matrix protein derivative (Emdogain). Int J Periodontics Restorative Dent 2000;20:374-81.
Heijl L, Heden G, Svärdström G, Ostgren A. Enamel matrix derivative (EMDOGAIN) in the treatment of intrabony periodontal defects. J Clin Periodontol 1997;24:705-14.
Venezia E, Goldstein M, Boyan BD, Schwartz Z. The use of enamel matrix derivative in the treatment of periodontal defects: A literature review and meta-analysis. Crit Rev Oral Biol Med 2004;15:382-402.
Trombelli L, Farina R. Clinical outcomes with bioactive agents alone or in combination with grafting or guided tissue regeneration. J Clin Periodontol 2008;35:117-35.
[Table 1], [Table 2], [Table 3]