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 xvii

1 Oral Wound Healing: An Overview 1
Hannu Larjava

Clotting and inflammation (chapters 2, 3 and 4) 1

Re-epithelialization and granulation tissue formation (chapters 5 and 6) 2

Angiogenesis (chapter 7) 3

Healing of extraction sockets (chapter 8) 4

Flap design for periodontal wound healing (chapter 9) 4

Regeneration of periodontal tissues (chapters 10 and 11) 5

Osteointegration and soft tissue healing around dental implants (chapter 12) 6

The pulp healing process (chapter 13) 7

Dermal wound healing and burn wounds (chapter 14) 7

Healing of large dentofacial defects (chapter 15) 8

References 9

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

Introduction 11

Primary hemostasis 12

Secondary hemostasis and the coagulation system 13

Tertiary hemostasis 16

Tissue factor 16

Von willebrand factor 17

Other coagulation factors 17

Cell-centric model of hemostasis: from initiation to propagation 18

The procoagulant membrane 20

Membrane particles 22

Endothelium and hemostasis 22

Pro- and anticoagulant functions 22

Platelets 24

Coagulation and wound healing 26

Limitations of the waterfall cascade model and screening laboratory tests 26

Implications for laboratory tests 27

Pre-surgical evaluation to prevent bleeding problems 27

Conclusions 32

References 32

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

Introduction 39

The innate immune response in wounds 39

Inflammatory cell infiltration into wounds 40

Inflammatory cell function in wounds 41

Cytokines and chemokines in wounds 44

Inflammation in oral mucosal wounds 47

Inflammation in fetal wounds 48

Role of inflammation in keloids 49

Inflammation and diabetic wounds 49

Conclusions 50

References 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 57

Complete resolution and tissue homeostasis is the ideal outcome of acute inflammation 58

Lipoxins, resolvins, protectins and maresins: semper vigilantes of anti-inflammation and pro-resolution 60

Resolution of inflammation is an actively regulated process in vivo 66

Resolvins and protectins are protective in experimental models of inflammatory diseases 67

Specialized pro-resolving lipid mediators in oral medicine: restoration of tissue homeostasis in experimental periodontitis 70

Resolution and wound healing 72

Anti-inflammation vs. Pro-resolution 72

Clinical implications and the development of stable analogs 74

Conclusions 74

Acknowledgments 75

References 75

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

Introduction 81

Keratinocytes form a protective barrier between an organism and its environment 81

Keratinocytes are activated rapidly to restore the epithelial barrier after wounding 82

Many different factors contribute to re-epithelialization 84

Final stages of re-epithelialization 106

Failure to re-epithelialize: chronic wounds 107

Conclusions 107

References 108

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

Introduction 125

Overview of connective tissue response to wounding 126

Wound healing stages 129

Origin and identity of wound fibroblasts 129

Granulation tissue formation 134

Connective tissue remodeling 151

Re-emergence of quiescent fibroblast phenotype 156

Specific features of oral mucosal wound healing 157

Conclusions 159

Acknowledgments 159

References 159

7 Angiogenesis and Wound Healing: Basic Discoveries, Clinical Implications and Therapeutic Opportunities 175
Peter J. Polverini

Introduction 175

How blood vessels develop 175

Early mechanistic insights into the angiogenic response: from solid tumors to chronic inflammation and wound healing 177

The role of other inflammatory cells in angiogenesis 179

Matrix molecules 180

Vascular endothelial growth factor and the modern era of angiogenesis research 181

Signaling networks of potential importance in wound neovascularization 182

Inhibitors of angiogenesis: important counterweights in wound neovascularization 184

The role of aberrant wound angiogenesis in the pathogenesis of diabetes mellitus 186

Conclusions 187

References 188

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

Healing of extraction sockets 195

Factors influencing the healing of extraction sockets 202

Healing of extraction sockets following immediate implant placement 203

Does the use of reconstructive technologies alter the healing of extraction sockets? 211

Conclusions 223

References 223

9 Flap Designs for Periodontal Healing 229
Leonardo Trombelli and Roberto Farina

Flap management, wound stability and periodontal regeneration 229

Flap designs to achieve primary closure 230

Surgical treatment of periodontal intraosseous defects: technical hints 237

Conclusions 240

References 241

10 Periodontal Regeneration: Experimental Observations – Clinical Consequences 243
Ulf M.E. Wikesjö, Cristiano Susin, Jaebum Lee, Douglas P. Dickinson and Giuseppe Polimeni

Introduction 243

Wound healing 244

Periodontal wound healing 245

Periodontal regeneration – new attachment 247

Wound stability 248

Space provision 251

Wound closure for primary intention healing 256

Conclusions 256

Acknowledgment 257

References 257

11 Biological Agents and Cell Therapies in Periodontal Regeneration 261
Hannu Larjava, Yi Yang, Edward Putnins, Jyrki Heino and Lari Häkkinen

Introduction 261

Adjunct growth factors in periodontal wound repair 261

PDGF and IGF-1 in periodontal regeneration 262

Platelet-rich plasma in periodontal therapy 265

FGF-2 in periodontal regeneration 265

Growth and differentiation factor-5 in periodontal regeneration 266

Other growth factors in periodontal regeneration 267

Bioactive collagen-derived peptide in periodontal regeneration (PepGen P-15®) 267

Enamel matrix proteins in periodontal regeneration and wound healing 269

Stem cells in periodontal wound healing 273

Conclusions 275

References 275

12 Wound Healing Around Dental Implants 287
Cristina Cunha Villar, Guy Huynh-Ba, Michael P. Mills and David L. Cochran

Introduction 287

Historical development 287

Titanium – the metal of choice 290

Healing following implant placement 291

Peri-implant soft tissue healing 291

Implant/peri-implant mucosa interface 292

Peri-implant hard tissue healing 294

From healing to clinical application 296

Implant stability testing 297

Wound healing and loading protocols 302

Conclusions 303

References 304

13 The Pulp Healing Process: From Generation to Regeneration 313
Stéphane Simon, Anthony J. Smith, Philip J. Lumley, Paul R. Cooper, and Ariane Berdal

From generation to regeneration 313

At the molecular level 323

Conclusion 328

References 328

14 Dermal Wound Healing and Burn Wounds 333
Anthony Papp

Introduction 333

Burn injury 333

Skin anatomy 334

Burn depth 336

Wound healing 338

Treatment 340

Special features in perioral burns 342

Conclusions 343

References 344

15 Healing of Large Dentofacial Defects 347
George K.B. Sándor, Robert P. Carmichael, Leena P. Ylikontiola, Ahmed Jan, Marc G. DuVal and Cameron M.L. Clokie

Introduction 347

The need for bone 349

Bone healing 349

Surgical maneuvers to induce and promote healing of large defects 355

Specifically difficult wounds 383

Conclusions 391

References 392

Index 397