Oral Wound Healing

Hannu Larjava, DDS, PhD, DipPerio is Professor and Chair of the Division of Periodontics at the University of British Columbia Faculty of Dentistry.

• Contributors xiii Preface xvii1 Oral Wound Healing: An Overview 1Hannu LarjavaClotting 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 92 Hemostasis, Coagulation and Complications 11Carol Oakley and Hannu LarjavaIntroduction 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 27Pre-surgical evaluation to prevent bleeding problems 27Conclusions 32References 323 Inflammation and Wound Healing 39Anna Turabelidze and Luisa Ann DiPietroIntroduction 39The innate immune response in wounds 39Inflammatory cell infiltration into wounds 40Inflammatory cell function in wounds 41Cytokines and chemokines in wounds 44Inflammation in oral mucosal wounds 47Inflammation in fetal wounds 48Role of inflammation in keloids 49Inflammation and diabetic wounds 49Conclusions 50References 504 Specialized Pro-resolving Lipid Derived Fatty Acid Mediators: Wiring the Circuitry of Effector Immune Homeostasis 57Gabrielle Fredman and Charles N. SerhanInflammation: 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 60Resolution 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 72Clinical implications and the development of stable analogs 74Conclusions 74Acknowledgments 75References 755 Re-epithelialization of Wounds 81Leeni Koivisto, Lari Häkkinen and Hannu LarjavaIntroduction 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 84Final stages of re-epithelialization 106Failure to re-epithelialize: chronic wounds 107Conclusions 107References 1086 Granulation Tissue Formation and Remodeling 125Lari Häkkinen, Hannu Larjava and Leeni KoivistoIntroduction 125Overview of connective tissue response to wounding 126Wound healing stages 129Origin and identity of wound fibroblasts 129Granulation tissue formation 134Connective tissue remodeling 151Re-emergence of quiescent fibroblast phenotype 156Specific features of oral mucosal wound healing 157Conclusions 159Acknowledgments 159References 1597 Angiogenesis and Wound Healing: Basic Discoveries, Clinical Implications and Therapeutic Opportunities 175Peter J. PolveriniIntroduction 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 in the pathogenesis of diabetes mellitus 186Conclusions 187References 1888 Wound Healing of Extraction Sockets 195Roberto Farina and Leonardo TrombelliHealing of extraction sockets 195Factors influencing the healing of extraction sockets 202Healing of extraction sockets following immediate implant placement 203Does the use of reconstructive technologies alter the healing of extraction sockets? 211Conclusions 223References 2239 Flap Designs for Periodontal Healing 229Leonardo Trombelli and Roberto FarinaFlap management, wound stability and periodontal regeneration 229Flap designs to achieve primary closure 230Surgical treatment of periodontal intraosseous defects: technical hints 237Conclusions 240References 24110 Periodontal Regeneration: Experimental Observations – Clinical Consequences 243Ulf M.E. Wikesjö, Cristiano Susin, Jaebum Lee, Douglas P. Dickinson and Giuseppe PolimeniIntroduction 243Wound healing 244Periodontal wound healing 245Periodontal regeneration – new attachment 247Wound stability 248Space provision 251Wound closure for primary intention healing 256Conclusions 256Acknowledgment 257References 25711 Biological Agents and Cell Therapies in Periodontal Regeneration 261Hannu Larjava, Yi Yang, Edward Putnins, Jyrki Heino and Lari HäkkinenIntroduction 261Adjunct growth factors in periodontal wound repair 261PDGF and IGF-1 in periodontal regeneration 262Platelet-rich plasma in periodontal therapy 265FGF-2 in periodontal regeneration 265Growth and differentiation factor-5 in periodontal regeneration 266Other growth factors in periodontal regeneration 267Bioactive collagen-derived peptide in periodontal regeneration (PepGen P-15®) 267Enamel matrix proteins in periodontal regeneration and wound healing 269Stem cells in periodontal wound healing 273Conclusions 275References 27512 Wound Healing Around Dental Implants 287Cristina Cunha Villar, Guy Huynh-Ba, Michael P. Mills and David L. CochranIntroduction 287Historical development 287Titanium – the metal of choice 290Healing following implant placement 291Peri-implant soft tissue healing 291Implant/peri-implant mucosa interface 292Peri-implant hard tissue healing 294From healing to clinical application 296Implant stability testing 297Wound healing and loading protocols 302Conclusions 303References 30413 The Pulp Healing Process: From Generation to Regeneration 313Stéphane Simon, Anthony J. Smith, Philip J. Lumley, Paul R. Cooper, and Ariane BerdalFrom generation to regeneration 313At the molecular level 323Conclusion 328References 32814 Dermal Wound Healing and Burn Wounds 333Anthony PappIntroduction 333Burn injury 333Skin anatomy 334Burn depth 336Wound healing 338Treatment 340Special features in perioral burns 342Conclusions 343References 34415 Healing of Large Dentofacial Defects 347George K.B. Sándor, Robert P. Carmichael, Leena P. Ylikontiola, Ahmed Jan, Marc G. DuVal and Cameron M.L. ClokieIntroduction 347The need for bone 349Bone healing 349Surgical maneuvers to induce and promote healing of large defects 355Specifically difficult wounds 383Conclusions 391References 392Index 397