Chemicals in Surgical Periodontal Therapy

Chemicals in Surgical Periodontal Therapy

 

Alexandrina L. Dumitrescu

Chemicals in Surgical Periodontal Therapy

Author Dr. Alexandrina L. Dumitrescu University of Tromsø Institute of Clinical Dentistry 9037 Tromsø Norway [email protected]

ISBN 978-3-642-18224-2 e-ISBN 978-3-642-18225-9 DOI 10.1007/978-3-642-18225-9 Springer Heidelberg Dordrecht London New York Library of Congress Control Number: 2011929929 © Springer-Verlag Berlin Heidelberg 2011 This work is subject to copyright. All rights are reserved, whether the whole or part of the material is ­concerned, specifically the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproduction on microfilm or in any other way, and storage in data banks. Duplication of this publication or parts thereof is permitted only under the provisions of the German Copyright Law of September 9, 1965, in its current version, and permission for use must always be obtained from Springer. Violations are liable to prosecution under the German Copyright Law. The use of general descriptive names, registered names, trademarks, etc. in this publication does not imply, even in the absence of a specific statement, that such names are exempt from the relevant ­protective laws and regulations and therefore free for general use. Product liability: The publishers cannot guarantee the accuracy of any information about dosage and application contained in this book. In every individual case the user must check such information by consulting the relevant literature. Cover design: eStudioCalamar, Figueres/Berlin Printed on acid-free paper Springer is part of Springer Science+Business Media (www.springer.com)

Preface

“…Nature doesn’t make useless things!” Aristotele, 384–322 a.C.

Periodontitis is an inflammatory disease characterized by the destruction of periodontal ligament, root cementum and alveolar bone as a tissue response to microbial plaque accumulation on the tooth root surface. For periodontal therapy that aims at the regeneration of the periodontal tissues, i.e., the restoration of their initial form, architecture and function, many choices of therapeutic procedures must be weighed before the proper one is chosen. Periodontal treatment includes conventional methods such as scaling and root planing, periodontal surgery with or without osseous surgery and new approaches such as guided tissue regeneration, root conditioning agents, the use of different grafting materials, enamel matrix derivative and their combination. In recent years, advances in molecular and cellular biology led to the study of growth factors’ potential role in promoting periodontal regeneration and their use as an alternative therapeutic approach. The examination of the patient, characteristics of the defect and knowledge of materials used in surgical periodontal therapy are all factors that must be entertained before the surgery begins. There are many options in periodontal regenerative surgery materials from which to choose. Knowledge of all of their advantages and disadvantages would allow a dentist to obtain the maximum of their benefits in the best interest of their patients. Alexandrina L. Dumitrescu

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Contents

1 Guided Tissue Regeneration Barriers......................................................... 1.1 Biologic Basis of Guided Tissue Regeneration (GTR).......................... 1.2 Summary of Studies Evaluating the Efficacy of GTR in the Treatment of Infrabony Defects..................................... 1.2.1 Histological Studies.................................................................. 1.2.2 Clinical Studies......................................................................... 1.3 Summary of Studies Evaluating the Efficacy of GTR in the Treatment of Furcation Lesions...................................... 1.3.1 Histological Studies.................................................................. 1.3.2 Clinical Studies......................................................................... 1.4 Summary of Studies Evaluating the Efficacy of GTR in the Treatment of Gingival Recession................................... 1.4.1 Histological Studies.................................................................. 1.4.2 Clinical Studies......................................................................... 1.5 Adjunctive Use of Antibiotics in GTR Treatment................................. 1.6 Advantages and Disadvantages of the Use of GTR Treatment............. 1.7 GTR Barriers for Periodontal Regeneration.......................................... 1.7.1 The Qualities of an “Optimal GTR Barrier” for Periodontal Regeneration.................................................... 1.7.2 Nonresorbable Membranes....................................................... 1.7.3 Bioresorbable Membranes........................................................ 1.7.4 New Trends in Guided Tissue Regeneration Barriers Development............................................................... References....................................................................................................... 2 Bone Grafts and Bone Graft Substitutes in Periodontal Therapy............ 2.1 Autogenous Grafts................................................................................. 2.1.1 Intraoral Autografts................................................................... 2.1.2 Extraoral Autografts.................................................................. 2.2 Allografts............................................................................................... 2.2.1 Freeze-Dried Bone Allografts (FDBA)..................................... 2.2.2 Demineralized Freeze-Dried Bone Allografts (DFDBA)......... 2.3 Xenografts.............................................................................................. 2.3.1 Anorganic Bovine-Derived Bone Xenograft (BDX)................ 2.3.2 Anorganic Porcine-Derived Bone Xenograft............................ 2.3.3 Coralline Calcium Carbonate....................................................

1 1 1 2 2 7 9 9 14 14 14 22 23 24 24 25 31 52 58 73 73 74 75 77 81 81 85 86 90 92

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Contents

2.4 Alloplasts (Alloplastic Synthetic Grafts)............................................... 2.4.1 Polymethylmethacrylate and Polyhydroxylethylmethacrylate (PMMA-PHEMA) Polymers.................................................... 2.4.2 Demineralized Dentin Matrix (DDM)...................................... 2.4.3 Hydroxylapatite (HA)............................................................... 2.4.4 Calcium Phosphate Cement (CPC)........................................... 2.4.5 b-Tricalcium Phosphate (TCP)................................................. 2.4.6 Calcium Sulfate......................................................................... 2.4.7 Bioactive Glasses (BG)............................................................. 2.4.8 Oily CaOH2 Suspension............................................................ 2.4.9 Porous Titanium Granules........................................................ 2.5 Composite Grafts................................................................................... 2.6 Factors Impacting Treatment Outcome................................................. 2.6.1 Criteria for Evaluation of Graft Success for Periodontal Regeneration............................................................................. 2.6.2 Factors Influencing Graft Success............................................ References....................................................................................................... 3 Enamel Matrix Derivative for Periodontal Tissue Regeneration.............. 3.1 EMD Formulation.................................................................................. 3.2 Clinical Safety of EMD......................................................................... 3.3 Biomimicry............................................................................................ 3.4 Mechanisms Underlying the Supportive Effects of EMD..................... 3.4.1 In Vitro and In Vivo Experiments............................................. 3.4.2 Animal Experiments................................................................. 3.4.3 Human Histological Studies..................................................... 3.5 Summary of Studies Evaluating the Efficacy of Emdogain in the Treatment of Infrabony Pockets (Vertical Bone Loss)................ 3.5.1 Nonsurgical Periodontal Therapy............................................. 3.5.2 Surgical Periodontal Therapy.................................................... 3.5.3 Hard Tissue Response After Emdogain Treatment of Intrabony Pockets................................................................. 3.5.4 Factors That Determine Emdogain Outcomes in the Treatment of Infrabony Defects...................................... 3.6 Summary of Studies Evaluating the Efficacy of Emdogain in the Treatment of Furcation Lesions................................................... 3.7 Summary of Studies Evaluating the Efficacy of Emdogain in the Treatment of supra-alveolar-type defects................................... 3.8 Summary of Studies Evaluating the Efficacy of EMD in the Treatment of Gingival Recession................................................. 3.9 Clinical Studies Evaluating the Effect of EMD on Early Wound Healing...................................................................................... 3.10 Clinical Studies Evaluating the Effect of EMD on Periodontal Healing of Replanted Teeth................................................................... 3.11 Advantages of the Use of Emdogain Gel............................................... References.......................................................................................................

94 94 95 95 103 107 114 116 121 123 123 125 125 126 127 145 145 146 146 146 146 147 147 171 171 171 189 192 195 197 198 208 208 209 209

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4 Chemical Root Surface Modifiers in the Treatment of Periodontal Disease................................................................................... 4.1 Citric Acid............................................................................................. 4.2 Tetracycline HCl.................................................................................... 4.3 EDTA..................................................................................................... References....................................................................................................... 5 The Use of Biologic Mediators for Periodontal Regeneration................... 5.1 Growth Factor Delivery for Oral and Periodontal Tissue Engineering................................................................................ 5.1.1 Biomaterials for Growth Factor Delivery................................. 5.1.2 Configurations of Growth Factor Delivery Carriers................. 5.2 The Use of Platelet-Rich Plasma (PRP) for Periodontal Regeneration.......................................................................................... 5.2.1 Preparation of Platelet-Rich Plasma......................................... 5.2.2 Handling and Application of Platelet-Rich Plasma.................. 5.2.3 Safety........................................................................................ 5.2.4 Human Studies on Platelet-Rich Plasma................................... 5.2.5 Potential Advantages and Limitations of PRP.......................... 5.3 Human Platelet–Derived Growth Factor-BB (PDGF)........................... 5.4 Peptide P-15........................................................................................... 5.5 Insulin-Like Growth Factors.................................................................. 5.6 Fibroblast Growth Factor-2.................................................................... 5.7 Transforming Growth Factor-b.............................................................. 5.8 Bone Morphogenetic Proteins............................................................... 5.9 Growth Factor Combinations................................................................. References.......................................................................................................

217 217 220 221 224 227 227 230 234 235 238 239 241 241 243 243 246 249 250 254 262 292 293

Index .................................................................................................................... 305

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Guided Tissue Regeneration Barriers

Guided tissue regeneration (GTR) typically refers to regeneration of periodontal attachment. Regeneration refers to the reproduction or reconstitution of a lost or injured part, in contrast to repair, which describes healing of a wound by tissue that does not fully restore the architecture or the function of the part. Periodontal regeneration is defined histologically as regeneration of the tooth’s supporting tissues, including alveolar bone, periodontal ligament, and cementum over a previously diseased root surface. New attachment is defined as the union of connective tissue or epithelium with a root surface that has been deprived of its original attachment apparatus. This new attachment may be epithelial adhesion and/or connective tissue adaptation or attachment and may include new cementum. It is to be distinguished from reattachment, which describes the reunion of epithelial and connective tissue with a root surface (American Academy of Periodontology 2001; Wang et al. 2005).

1.1 Biologic Basis of Guided Tissue Regeneration (GTR) Successful periodontal regeneration relies on the re-formation of an epithelial seal, deposition of new acellular extrinsic fiber cementum and insertion of functionally oriented connective tissue fibers into the root surface, and restoration of alveolar bone height (Villar and Cochran 2010). Following flap elevation, the instrumented root surface can be repopulated by epithelial cells, gingival connective tissue cells, bone cells and periodontal ligament cells. Under normal healing conditions, epithelial cells rapidly migrate in an apical direction to reach the most apical portion of the instrumentation, forming a long junctional epithelium

and preventing the formation of a new attachment. The barrier membrane prevents gingival epithelium and connective tissue expansion and allows cells from the periodontal ligament and bone to repopulate the root surface and to form a new periodontal attachment (Cortellini and Tonetti 2000; Nyman et al. 1980; Karring et  al. 1980, 1985; Bosshardt and Sculean 2009) (Figs. 1.1 and 1.2). Besides favoring selective repopulation of the wound area, physical barriers are also thought to provide protection to the blood clot during the early phases of healing and to ensure space maintenance for ingrowth of a new periodontal apparatus. GTR membranes, as physical barriers, however, provide no biologic effects on the differentiation and proliferation of mesenchymal and periodontal ligament cells, which is likely to limit their clinical efficacy (Villar and Cochran 2010).

1.2 Summary of Studies Evaluating the Efficacy of GTR in the Treatment of Infrabony Defects According to the classification by Goldman and Cohen (1958), suprabony defects are those where the base of the pocket is located coronal to the alveolar crest. Infrabony defects, on the other hand, are defined by the apical location of the base of the pocket with respect to the residual alveolar crest (Papapanou and Tonetti 2000). With regard to infrabony defects, two types of defects can be recognized: intrabony defects and craters. Intrabony defects are bony defects whose infrabony component affects primarily one tooth, while in craters the defect affects two adjacent root surfaces to a similar extent. Intrabony defects have been classified according to their morphology in terms

A.L. Dumitrescu, Chemicals in Surgical Periodontal Therapy, DOI: 10.1007/978-3-642-18225-9_1, © Springer-Verlag Berlin Heidelberg 2011

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1  Guided Tissue Regeneration Barriers

Fig. 1.2  Light micrograph illustrating true periodontal regeneration as demonstrated by new periodontal ligament fibers (NPLF) inserting into new bone (NB) and new cementum (NC). (Paraffin section, oxone−aldehydefuchsin−Halmi stain.) (Bosshardt and Sculean 2009. Reprinted with permission from John Wiley & Sons) Fig. 1.1  Light micrograph illustrating formation of a long junctional epithelium (LJE) ending at the coronal-most end of regenerated cementum (C). D dentin. (Paraffin section stained with hematoxylin and eosin.) (Bosshardt and Sculean 2009. Reprinted with permission from John Wiley & Sons)

of residual bony walls, width of the defect (or radiographic angle), and in terms of their topographic extension around the tooth. Three-wall, two-wall and one-wall defects have been defined on the basis of the number of residual alveolar bone walls. This represents the primary classification system. Frequently, intrabony defects present a complex anatomy consisting of a three-wall component in the most apical portion of the defect, and two- and/or one-wall components in the more superficial portions. Such defects are frequently referred to as combination defects. Hemiseptal defects, that is, vertical defects in the presence of adjacent roots and where half of a septum remains on one tooth, represent a special case of one-wall defects (Glossary of Periodontal Terms 1993; Papapanou and Tonetti 2000).

1.2.1 Histological Studies Histological evaluation, however, remains the only reliable method of determining the nature of the attachment apparatus resulting from regenerative procedures. Several studies in animals (Aukhil et  al. 1983, 1986; Caffesse et al. 1988, 1994; Caton et al. 1992; Gottlow et al. 1984, 1994; Nyman et al. 1982a; Elharar et al. 1998; Batista et  al. 1999; Blumenthal et  al. 2003) and some human biopsy material (Becker et  al. 1987; Cortellini et  al. 1993a, b; Gottlow et al. 1986; Nyman et al. 1982b; Stahl and Froum 1991; Stahl et al. 1990; Laurell et al. 2006) have documented that guided tissue regeneration is capable of promoting new attachment formation.

1.2.2 Clinical Studies The reported outcomes indicate that the application of nonresorbable or bioresorbable barrier membranes

1.2  Summary of Studies Evaluating the Efficacy of GTR in the Treatment of Infrabony Defects

consistently and predictably results in clinical improvements in intrabony defects (Cortellini and Tonetti 2000).

1.2.2.1 Therapeutic End-Points of Success The primary outcomes and desirable clinical results of the regenerative treatment of intrabony defects are (1) gain of clinical attachment and bone, (2) fill of the intrabony component of the defect, (3) reduction of pocket depth and (4) minimal gingival recession (Cortellini and Tonetti 2000). The main methods used for evaluation include histology, direct measurement of bone, periodontal probing and radiographic analysis (Reddy and Jeffcoat 1999).

1.2.2.2 Comparison GTR Alone Versus Control/ Placebo/Open Flap Debridement Several systematic reviews and meta-analyses have reported greater benefits to GTR than open-flap debridement in the treatment of intrabony defects (Laurell et al. 1998; Cortellini and Tonetti 2000; Needleman et  al. 2001, 2005; Murphy and Gunsolley 2003; Aichelmann-Reidy and Reynolds 2008). Laurell et  al. (1998) reviewed studies presented during the last 20  years on the surgical treatment of intrabony defects. GTR resulted in significant pocket reduction, a clinical attachment level (CAL) gain of 4.2 mm, and bone fill averaging 3.2 mm. The weighted mean of the evidence reported in the 11 studies reviewed by Cortellini and Tonetti (2000) indicated that the gain of clinical attachment in sites treated with guided tissue regeneration was 3.4 ± 1.8 mm (95% CI: 3.0–3.7 mm), while the access flap resulted in a mean gain of 1.8 ± 1.4 mm (95% CI: 1.5–2.1 mm). The analysis of the reported clinical outcomes strongly suggests an added benefit derived from the placement of barrier membranes after elevation of an access flap. The frequency distribution of clinical attachment level changes at 1 year has been evaluated by subdividing the data into five classes of probing attachment level changes: loss of attachment, gain of 0–1 mm, gain of 2–3 mm, gain of 4–5 mm and gain of 6  mm or more. Only 2.7% of 651 treated cases lost attachment, while gains of less than 2  mm were observed in 11% of the cases. Most of the sites gained

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considerable attachment. In fact, gains of 2–3  mm were observed in 24.8% of the cases, gains of 4–5 mm in 41.3%, and gains of 6  mm or more in 21.2% of defects. These encouraging data demonstrate that guided tissue regeneration is not only efficacious, but also predictable. Regarding changes in bone levels, bone gains ranged from 1.1 to 4.3 mm and seemed to correlate well with the gains in clinical attachment. Reduction of pocket depths is one of the critical endpoints of most periodontal procedures, including guided tissue regeneration. An important parameter to evaluate the successful outcomes of guided tissue regeneration, therefore, is the depth of the residual pockets. At 1  year, the weighted mean of residual pocket depths was 3.3 ± 1.2  mm, with a 95% confidence interval ranging from 3.2 to 3.5 mm (Cortellini and Tonetti 2000). Needleman et  al. (2001) evaluated 23 RCT of at least 12  months duration comparing GTR (with or without graft materials) with open flap debridement for the treatment of periodontal infrabony defects up to October 2000. Furcation involvements and studies specifically treating early-onset diseases were excluded. For attachment level change, the weighted mean difference between GTR alone and open flap debridement was 1.11  mm (95% CI: 0.63–1.59, chi-square for ­heterogeneity 31.4 (df = 9), P