oral wound healing (larjava/oral wound healing) || front matter

Download Oral Wound Healing (Larjava/Oral Wound Healing) || Front Matter

Post on 18-Feb-2017




4 download

Embed Size (px)


  • Oral Wound HealingCell Biology and Clinical Management

    Edited by

    Hannu LarjavaProfessor and Chair, Division of PeriodonticsFaculty of DentistryUniversity of British ColumbiaVancouverBC, Canada

    A John Wiley & Sons, Ltd., Publication

    Larjava_ffirs.indd iiiLarjava_ffirs.indd iii 2/3/2012 12:50:13 PM2/3/2012 12:50:13 PM

  • This edition fi rst published 2012 by John Wiley & Sons, Inc 2012 John Wiley & Sons, Inc

    Wiley-Blackwell is an imprint of John Wiley & Sons, Inc formed by the merger of Wileys global Scientifi c, Technical and Medical business with Blackwell Publishing.

    Registered Offi ceJohn Wiley & Sons, Ltd, The Atrium, Southern Gate, Chichester, West Sussex, PO19 8SQ, UK

    Editorial Offi ces2121 State Avenue, Ames, Iowa 50014-8300, USAThe Atrium, Southern Gate, Chichester, West Sussex, PO19 8SQ, UK9600 Garsington Road, Oxford, OX4 2DQ, UK

    For details of our global editorial offi ces, for customer services and for information about how to apply for permission to reuse the copyright material in this book please see our website at www.wiley.com/wiley-blackwell.

    Authorization to photocopy items for internal or personal use, or the internal or personal use of specifi c clients, is granted by Blackwell Publishing, provided that the base fee is paid directly to the Copyright Clearance Center, 222 Rosewood Drive, Danvers, MA 01923. For those organizations that have been granted a photocopy license by CCC, a separate system of payments has been arranged. The fee codes for users of the Transactional Reporting Service are ISBN-13: 978-0-8138-0481-1/2007.

    Designations used by companies to distinguish their products are often claimed as trademarks. All brand names and product names used in this book are trade names, service marks, trademarks or registered trademarks of their respective owners. The publisher is not associated with any product or vendor mentioned in this book. This publication is designed to provide accurate and authoritative information in regard to the subject matter covered. It is sold on the understanding that the publisher is not engaged in rendering professional services. If professional advice or other expert assistance is required, the services of a competent professional should be sought.

    Library of Congress Cataloging-in-Publication Data

    Oral wound healing : cell biology and clinical management / edited by Hannu Larjava. p. ; cm. Includes bibliographical references and index. ISBN 978-0-8138-0481-1 (hardcover : alk. paper)I. Larjava, Hannu.[DNLM: 1. Periodontal Diseasesrehabilitation. 2. Mouthinjuries. 3. Oral Surgical Proceduresrehabilitation. 4. Wound Healing. WU 240] 617.632dc23


    A catalogue record for this book is available from the British Library.

    Wiley also publishes its books in a variety of electronic formats. Some content that appears in print may not be available in electronic books.

    Set in 10/12pt Times by SPi Publisher Services, Pondicherry, India

    1 2012

    Larjava_ffirs.indd ivLarjava_ffirs.indd iv 2/3/2012 12:50:13 PM2/3/2012 12:50:13 PM

  • Contents

    Contributors xiii

    Preface xvii

    1 Oral Wound Healing: An Overview 1 Hannu Larjava

    Clotting and inflammation (chapters 2, 3 and 4) 1Re-epithelialization and granulation tissue formation (chapters 5 and 6) 2Angiogenesis (chapter 7) 3Healing of extraction sockets (chapter 8) 4Flap design for periodontal wound healing (chapter 9) 4Regeneration of periodontal tissues (chapters 10 and 11) 5Osteointegration and soft tissue healing around

    dental implants (chapter 12) 6The pulp healing process (chapter 13) 7Dermal wound healing and burn wounds (chapter 14) 7Healing of large dentofacial defects (chapter 15) 8References 9

    2 Hemostasis, Coagulation and Complications 11 Carol Oakley and Hannu Larjava

    Introduction 11Primary hemostasis 12Secondary hemostasis and the coagulation system 13Tertiary hemostasis 16Tissue factor 16Von willebrand factor 17Other coagulation factors 17Cell-centric model of hemostasis: from initiation to propagation 18The procoagulant membrane 20Membrane particles 22Endothelium and hemostasis 22Pro- and anticoagulant functions 22Platelets 24Coagulation and wound healing 26Limitations of the waterfall cascade model and screening laboratory tests 26Implications for laboratory tests 27

    Larjava_ftoc.indd vLarjava_ftoc.indd v 2/14/2012 5:31:55 PM2/14/2012 5:31:55 PM

  • vi Contents

    Pre-surgical evaluation to prevent bleeding problems 27 Medical history 27 Diet and herbal supplements 29 Clinical examination 29 Presurgical planning 30 Control of intra-operative/primary bleeding 30 Post-operative/secondary bleeding 31Conclusions 32References 32

    3 Inflammation and Wound Healing 39 Anna Turabelidze and Luisa Ann DiPietro

    Introduction 39The innate immune response in wounds 39Inflammatory cell infiltration into wounds 40Inflammatory cell function in wounds 41 Neutrophils 41 Mast cells 42 Macrophages 43 T lymphocytes 43 Gamma delta T-cells or dentritic epidermal T-cells (DETCs) 44Cytokines and chemokines in wounds 44 Interleukin-1 (IL-1) 45 Interleukin-6 (IL-6) 45 Interleukin-8 (IL-8 or CXCL8) 45 Tumor necrosis factor (TNF alpha) 46 Macrophage chemoattractant protein (MCP-1 or CCL2) 46 Interferon inducible protein 10 (IP-10 or CXCL10) 46 Stromal cell-derived factor (SDF-1 or CXCL12) 46 Transforming growth factor-beta (TGF-b) 47Inflammation in oral mucosal wounds 47Inflammation in fetal wounds 48Role of inflammation in keloids 49Inflammation and diabetic wounds 49Conclusions 50References 50

    4 Specialized Pro-resolving Lipid Derived Fatty Acid Mediators: Wiring the Circuitry of Effector Immune Homeostasis 57

    Gabrielle Fredman and Charles N. Serhan

    Inflammation: the cardinal signs 57Complete resolution and tissue homeostasis is the ideal

    outcome of acute inflammation 58Lipoxins, resolvins, protectins and maresins: semper vigilantes

    of anti-inflammation and pro-resolution 60 Lipoxins 62 Resolvins 62

    Larjava_ftoc.indd viLarjava_ftoc.indd vi 2/14/2012 5:31:55 PM2/14/2012 5:31:55 PM

  • Contents vii

    Protectins 65 Maresins 65Resolution of inflammation is an actively regulated

    process in vivo 66Resolvins and protectins are protective in experimental

    models of inflammatory diseases 67Specialized pro-resolving lipid mediators in oral medicine:

    restoration of tissue homeostasis in experimental periodontitis 70Resolution and wound healing 72Anti-inflammation vs. Pro-resolution 72 Resolution toxicity 73Clinical implications and the development of stable analogs 74Conclusions 74Acknowledgments 75References 75

    5 Re-epithelialization of Wounds 81 Leeni Koivisto, Lari Hkkinen and Hannu Larjava

    Introduction 81Keratinocytes form a protective barrier between an organism

    and its environment 81Keratinocytes are activated rapidly to restore the epithelial

    barrier after wounding 82Many different factors contribute to re-epithelialization 84 Keratinocytes become exposed to novel extracellular

    matrix molecules in wounds 85 Integrins are signaling molecules that mediate cell adhesion

    to extracellular matrix and cell migration 87 Cytokines and growth factors are important mediators

    of wound healing 95 Serine proteases and matrix metalloproteinases modulate

    extracellular matrix and generate biologically active molecules 102 Levels of divalent cations in the wound fluid affect

    re-epithelialization 105 Wound-induced electrical field directs re-epithelialization 106Final stages of re-epithelialization 106Failure to re-epithelialize: chronic wounds 107Conclusions 107References 108

    6 Granulation Tissue Formation and Remodeling 125 Lari Hkkinen, Hannu Larjava and Leeni Koivisto

    Introduction 125Overview of connective tissue response to wounding 126Wound healing stages 129Origin and identity of wound fibroblasts 129Granulation tissue formation 134

    Larjava_ftoc.indd viiLarjava_ftoc.indd vii 2/14/2012 5:31:55 PM2/14/2012 5:31:55 PM

  • viii Contents

    Activation of connective tissue cells 135 Cell proliferation 138 Cell migration 141 Matrix deposition and wound contraction 144 Transforming growth factor-b 149Connective tissue remodeling 151 Downregulation of cell proliferation and cellularity 152 ECM degradation 152 ECM reorganization and increased stability by collagen

    cross-linking 154 Downregulation of ECM production 155Re-emergence of quiescent fibroblast phenotype 156Specific features of oral mucosal wound healing 157Conclusions 159Acknowledgments 159References 159

    7 Angiogenesis and Wound Healing: Basic Discoveries, Clinical Implications and Therapeutic Opportunities 175

    Peter J. Polverini

    Introduction 175How blood vessels develop 175Early mechanistic insights into the angiogenic response:

    from solid tumors to chronic inflammation and wound healing 177The role of other inflammatory cells in angiogenesis 179Matrix molecules 180Vascular endothelial growth factor and the modern era

    of angiogenesis research 181Signaling networks of potential importance in wound

    neovascularization 182Inhibitors of angiogenesis: important counterweights in wound

    neovascularization 184The role of aberrant wound angiogenesis inthe pathogenesis

    of diabetes mellitus 186Conclusions 187References 188

    8 Wound Healing of Extraction Sockets 195 Roberto Farina and Leonardo Trombelli

    Healing of extraction sockets 195 Histological aspects 195 Clinical aspects 199Factors influencing the healing of extraction sockets 202 Smoking 202 Flapless tooth extraction 202 Location of the edentulous site 202

    Larjava_ftoc.indd viiiLarjava_ftoc.indd viii 2/14/2012 5: