Edited by Joshua Boateng received his Ph.D. in Pharmaceutical Sciences (Drug Delivery and Formulation) at the University of Strathclyde, Glasgow, under a Pfizer-sponsored project to develop novel formulations for wound healing applications. He has authored more than 70 peer-reviewed scientific publications and is on the Editorial Board of 3 international scientific journals, including the Journal of Pharmaceutical Sciences. He won the 2009 University of Greenwich Early Career Research Award and has reviewed for more than 60 international scientific journals. He is currently a Reader (Associate Professor) in Pharmaceutical Science and Formulation Technologies at the University of Greenwich.

• List of Contributors xiiiSeries Preface xviiPreface xix1 Chronic Wound Healing: Molecular and Biochemical Basis 1Sophia Tate and Keith Harding1.1 Introduction 11.2 Acute Wound Healing 11.3 Categories of Chronic Wound 31.3.1 Pressure Ulcers 31.3.2 Venous Stasis Ulcers 41.3.3 Ischaemic Ulcers 41.3.4 Diabetic Foot Ulcers 41.4 How a Chronic Wound Develops: Intrinsic Components 41.4.1 Cell Phenotype 51.4.2 Immune Cells and Inflammatory Mediators 61.4.3 Reactive Oxygen Species 81.4.4 Growth Factors 81.4.5 The Role of Matrix Metalloproteinases 121.5 How a Chronic Wound Develops: Extrinsic Factors 131.5.1 Infection 131.5.2 Nutrition 131.5.3 Tobacco Smoking 141.5.4 Hypoxia and Ischaemia–Reperfusion Injury 151.6 Concluding Remarks 15References 162 Clinical Perspectives for Treating Chronic Wounds 21Barun Majumder, Kirstie Lane, Diane Beck, Sandeep Singh and Duniya Majumder2.1 Background 212.2 Aetiology of Diabetic Foot Ulcers 222.3 Standard of Care for Treatment of Diabetic Foot Ulcers 222.4 Commonly Used Wound Dressings for Diabetic Foot Ulcers and Their Mechanism of Action 222.5 Absorbent and Superabsorbent Dressings 232.6 Alginates 232.7 Films 232.8 Foams 242.9 Honeys 242.10 Hydrogels 252.11 The Role of a Split Thickness Skin Graft in Diabetic Foot Ulcers 252.12 Negative Pressure Wound Therapy 252.13 Larval Therapy 272.14 Clinical Case Studies from Multidisciplinary Diabetic Foot Clinic 272.14.1 Neuropathic Wound 272.14.2 Ischaemic Wound 292.14.3 Neuro-Ischaemic Wound 312.14.4 Osteomyelitis 332.14.5 Charcot’s Foot 352.14.6 Necrotising Fasciitis in a Patient with Diabetes 362.15 Summary 39Acknowledgements 39References 393 Prediction, Prevention, Assessment, and Management of Skin Tears in the Aging Population 43Kimberly LeBlanc and Karen Campbell3.1 Introduction 433.2 Skin Tear Prevalence and Incidence 443.3 Predicting Skin Tears 453.4 Prevention 473.5 ISTAP Risk Reduction Program 493.5.1 General Health 493.5.2 Mobility 503.5.3 Skin 513.6 Assessment 523.7 Management 543.8 Treatment 543.9 Conclusion 55References 554 Importance of Debriding and Wound Cleansing Agents in Wound Healing 59Gwendolyn Cazander, Bianca K. den Ottelander, Sandra Kamga, Martijn C.H.A. Doomen, Tim H.C. Damen and Anne Marie E. van Well4.1 What is Debridement? 594.2 The History of Debridement 594.3 Why Undertake Debridement? 604.4 Debridement Techniques and Wound Cleansing Agents 624.4.1 Mechanical Debridement 624.4.2 Biological Debridement 724.4.3 Enzymatic Debridement 744.4.4 Autolytic Debridement 774.4.5 Wound Cleansing 794.4.6 Other Debridement Therapies 804.5 What is the Future of Debridement? 81References 825 Treatment of Mixed Infections in Wounds 91Asif Ahmed and Joshua Boateng5.1 Introduction 915.1.1 Wound Healing Process 925.1.2 Types of Chronic Wounds 925.2 Prevalence of Mixed Infections 945.2.1 Bacterial–Fungal Interactions 955.2.2 Bacterial–Bacterial Interactions 985.2.3 Host Responses to Mixed Infections and Drug Resistance 995.3 Management of Mixed Infected Wounds 1005.3.1 Clinical and Microbiological Diagnosis 1015.3.2 Debridement and Cleansing 1015.3.3 Antimicrobial Therapies 1025.3.4 Hyperbaric Oxygen Therapy 1045.3.5 Phage Therapy 1045.4 Summary and Future Perspectives 104References 1056 Treatment of Biofilms in Infected Wounds 115Philip Debrah, Awo Afi Kwapong and Mansa Fredua-Agyeman6.1 Introduction 1156.2 Why and How Biofilms Form 1166.3 Wound Biofilms 1186.3.1 Wound Healing 1196.4 Biofilms and Wounds 1196.4.1 Simulation of Biofilms in Wounds 1206.5 Treatment of Biofilms in Wounds 1266.5.1 Biofilm Eradication 1266.5.2 Current Treatment Protocols 1286.6 Clinical Examples 1286.7 Summary 128References 1307 Freeze-Dried Wafers for Wound Healing 137Shiow-Fern Ng7.1 Introduction 1377.2 Wafer as a Modern Wound Dressing 1387.3 Freeze-Drying Process 1397.4 Wafer Preparation 1407.5 Wafer Assessments 1417.5.1 Morphology 1427.5.2 Swelling Index 1447.5.3 Mechanical Properties 1457.5.4 In Vitro Drug Release 1457.5.5 Cell Viability 1467.6 Wafer Biopolymers 1467.6.1 Alginate 1477.6.2 Chitosan 1487.6.3 Carboxymethylcellulose 1497.7 Conclusion 150References 1508 Silver and Silver Nanoparticle-Based Antimicrobial Dressings 157Joshua Boateng and Ovidio Catanzano8.1 Introduction 1578.1.1 Brief History of Silver as an Antibiotic 1598.1.2 Mechanism of Action 1608.1.3 Bacterial Resistance to Silver 1648.2 Silver Dressings in Wound Healing 1678.2.1 Silver-Based Antimicrobial Dressings 1698.2.2 Silver Nanoparticle-Based Antimicrobial Dressings 1708.3 Cost-Effectiveness of Silver Dressings 1758.4 Concluding Remarks 176References 1779 Hydrogel Dressings 185Galiya S. Irmukhametova, Grigoriy A. Mun and Vitaliy V. Khutoryanskiy9.1 Introduction 1859.1.1 Classification by Origin of Materials Used to Prepare Hydrogels 1869.1.2 Classification by Composition and Structure of Hydrogels 1869.1.3 Classification by the Type of Cross-Linking 1879.1.4 Classification Based on the Shape and Dimensions of Hydrogels 1879.1.5 Classification Based on the Charge of Macromolecules Forming Hydrogels 1879.1.6 Classification Based on Functional Properties of the Hydrogels 1879.2 Mechanism of Hydrogel Swelling 1879.2.1 Swelling of Temperature-Sensitive Hydrogels and Their Application in Wound Healing 1899.2.2 Swelling of Light-Sensitive Hydrogels 1909.2.3 Swelling of Electro-Sensitive Hydrogels 1919.3 Application of Hydrogels as Wound Dressings 1919.4 Industrial Methods for the Synthesis of Hydrogels for Wound Dressings 1939.4.1 Polymerization Methods 1939.4.2 Cross-Linking of Polymers 1959.5 Antimicrobial Hydrogels with Special Additives 1989.6 Conclusion 200Acknowledgments 201References 20110 Gene Therapy for the Treatment of Chronic Wounds 209Marcos Garcia-Fuentes10.1 Introduction 20910.2 Pharmacodynamics of Gene Therapy in Chronic Wounds 21010.2.1 Signalling Supplementation 21010.2.2 Pathway Inhibition 21110.3 Administration Routes and Methods 21210.3.1 Systemic Delivery 21210.3.2 Topical Delivery 21210.3.3 Intralesional Delivery 21310.4 Gene Delivery Systems 21310.4.1 Physical Methods 21410.4.2 Viral Vectors 21510.4.3 Chemical Delivery Systems 21710.4.4 Gene-Activated Matrices 22010.5 Clinical Evaluation 22110.6 Conclusion 226Acknowledgements 226References 22711 Honey in Wound Healing 235Emi Maruhashi11.1 The History of Honey 23511.2 Composition 23611.3 Honey Research 23611.4 Medical Grade Honey 23711.5 Modes of Action 23811.6 Applications and Specific Wound Types 24211.7 Practical Considerations 24611.8 Novel Concepts and Conclusions 247References 24812 Regeneration Using Tissue Engineered Skin Strategies 255Lucília P. da Silva, Mariana T. Cerqueira and Alexandra P. Marques12.1 Introduction 25512.2 Skin Physiology and Wounding 25612.3 Skin Tissue Engineering 25812.4 Evolving Skin Tissue Engineering Strategies 25912.4.1 Balancing the Inflammatory Phase 26112.4.2 Enhancement of Re-Epithelialization 26312.4.3 Target of Dermal Matrix Synthesis and Remodeling 26912.4.4 Re-Establishment of the Vascular Network 27012.4.5 Innervation Shaping 28012.4.6 Appendages and Pigmentation 28112.5 Conclusion 282References 28313 Local Delivery of Growth Factors Using Wound Dressings 291Ovidio Catanzano and Joshua Boateng13.1 Wound Dressings as Delivery Platforms for Growth Factors 29113.2 Growth Factors Involved in the Wound Healing Process 29213.3 Local Delivery of Growth Factors Using Wound Dressings 29613.4 Integration of Platelet-Rich Plasma in Wound Dressings 29913.5 Enhancing Local Growth Factor Expression Using Gene Therapy 30013.6 Wound Delivery of Growth Factors from Living Systems 30213.7 Regulatory Considerations 30513.8 Conclusions and Future Perspectives 306References 30714 Electrospinning Technologies in Wound Dressing Applications 315Giuseppina Sandri, Silvia Rossi, Maria Cristina Bonferoni, Carla Caramella and Franca Ferrari14.1 Introduction 31514.2 Basic Concept and Electrospinning Set-Up 31614.3 Parameters Affecting the Electrospinning Process 31814.4 Process Parameters 31914.4.1 Electric Field Strength 31914.4.2 Flow Rate 31914.4.3 Needle-to-Collector Distance 32014.4.4 Collector and Needle Types 32014.5 Solution Parameters 32114.5.1 Molecular Weight and Polymer Concentration 32114.5.2 Surface Tension 32214.5.3 Conductivity/Surface Charge Density 32214.5.4 Environmental Parameters 32214.6 Biomedical Applications of Nanofibrous Membranes 32314.6.1 Wound Dressings and Wound Healing 32314.6.2 Electrospun Dressings 32514.7 Chemicophysical and Biopharmaceutical Characterizations 32514.8 Dressing/Scaffold Parameters Affecting Cell Functions 32714.9 Materials for Fabricating Nanofibers 32814.9.1 Biopolymers 32814.10 Concluding Remarks 333References 33315 The Place of Biomaterials in Wound Healing 337Annalisa Bianchera, Ovidio Catanzano, Joshua Boateng and Lisa Elviri15.1 Introduction to Biomaterials for Wound Healing 33715.1.1 Definition of Biomaterials 33715.1.2 Functional Requirements of Wound Repair Biomaterials 33815.1.3 Classification of Biomaterials Commonly Used in Wound Healing 33815.2 Synthetic Biomaterials for Wound Healing 33915.2.1 Polyurethanes and their Derivatives 34015.2.2 Poly l-Lactic Acid 34015.2.3 Poly(Ethylene Glycol) 34115.2.4 Polycaprolactone 34115.2.5 Poly(Glycolic Acid) and Poly(Lactic-co-Glycolic Acid) 34215.3 Natural Biomaterials for Wound Healing 34315.3.1 Polysaccharide-Based Biomaterials 34315.3.2 Protein-Based Biomaterials 34815.4 Application of Biomaterials in Wound Healing 35015.4.1 Traditional and Impregnated Dressings 35015.4.2 Hydrogels 35215.4.3 Film Dressings 35315.4.4 Foam Dressings 35415.4.5 Nanofiber-Based Dressings 35515.4.6 Three-Dimensional Printed Dressings 35615.5 New Trends in Biomaterials for Wound Healing 35715.5.1 Extracellular Matrix-Derived Biomaterials 35715.5.2 Tissue Engineered Skin Substitutes 35715.6 Conclusions and Future Perspectives 358References 35916 Wound Dressings and Pressure Ulcers 367Michael Clark16.1 Overview 36716.2 Introduction to Pressure Ulcers 36716.3 The Impact of Pressure Ulcers 36916.4 Managing Pressure Ulcers 37016.5 Wound Dressings in Pressure Ulcer Treatment 37116.6 Pressure Ulcer Prevention and Wound Dressings 37716.6.1 Pressure Ulcers at the Nose 37816.6.2 Pressure Ulcers at the Heel 37816.6.3 Pressure Ulcers at the Sacrum 37816.7 Conclusions 380References 38017 3D Printed Scaffolds for Wound Healing and Tissue Regeneration 385Atabak Ghanizadeh Tabriz, Dennis Douroumis and Joshua Boateng17.1 Introduction 38517.2 3D Printing 38617.3 Laser-Based Bioprinting 38717.4 Jet-Based Printing 38917.5 Extrusion-Based Printing 39117.6 Hybrid Printing 39317.7 Conclusions 395References 395Index 399

Edited by Joshua Boateng received his Ph.D. in Pharmaceutical Sciences (Drug Delivery and Formulation) at the University of Strathclyde, Glasgow, under a Pfizer-sponsored project to develop novel formulations for wound healing applications. He has authored more than 70 peer-reviewed scientific publications and is on the Editorial Board of 3 international scientific journals, including the Journal of Pharmaceutical Sciences. He won the 2009 University of Greenwich Early Career Research Award and has reviewed for more than 60 international scientific journals. He is currently a Reader (Associate Professor) in Pharmaceutical Science and Formulation Technologies at the University of Greenwich.

• List of Contributors xiiiSeries Preface xviiPreface xix1 Chronic Wound Healing: Molecular and Biochemical Basis 1Sophia Tate and Keith Harding1.1 Introduction 11.2 Acute Wound Healing 11.3 Categories of Chronic Wound 31.3.1 Pressure Ulcers 31.3.2 Venous Stasis Ulcers 41.3.3 Ischaemic Ulcers 41.3.4 Diabetic Foot Ulcers 41.4 How a Chronic Wound Develops: Intrinsic Components 41.4.1 Cell Phenotype 51.4.2 Immune Cells and Inflammatory Mediators 61.4.3 Reactive Oxygen Species 81.4.4 Growth Factors 81.4.5 The Role of Matrix Metalloproteinases 121.5 How a Chronic Wound Develops: Extrinsic Factors 131.5.1 Infection 131.5.2 Nutrition 131.5.3 Tobacco Smoking 141.5.4 Hypoxia and Ischaemia–Reperfusion Injury 151.6 Concluding Remarks 15References 162 Clinical Perspectives for Treating Chronic Wounds 21Barun Majumder, Kirstie Lane, Diane Beck, Sandeep Singh and Duniya Majumder2.1 Background 212.2 Aetiology of Diabetic Foot Ulcers 222.3 Standard of Care for Treatment of Diabetic Foot Ulcers 222.4 Commonly Used Wound Dressings for Diabetic Foot Ulcers and Their Mechanism of Action 222.5 Absorbent and Superabsorbent Dressings 232.6 Alginates 232.7 Films 232.8 Foams 242.9 Honeys 242.10 Hydrogels 252.11 The Role of a Split Thickness Skin Graft in Diabetic Foot Ulcers 252.12 Negative Pressure Wound Therapy 252.13 Larval Therapy 272.14 Clinical Case Studies from Multidisciplinary Diabetic Foot Clinic 272.14.1 Neuropathic Wound 272.14.2 Ischaemic Wound 292.14.3 Neuro-Ischaemic Wound 312.14.4 Osteomyelitis 332.14.5 Charcot’s Foot 352.14.6 Necrotising Fasciitis in a Patient with Diabetes 362.15 Summary 39Acknowledgements 39References 393 Prediction, Prevention, Assessment, and Management of Skin Tears in the Aging Population 43Kimberly LeBlanc and Karen Campbell3.1 Introduction 433.2 Skin Tear Prevalence and Incidence 443.3 Predicting Skin Tears 453.4 Prevention 473.5 ISTAP Risk Reduction Program 493.5.1 General Health 493.5.2 Mobility 503.5.3 Skin 513.6 Assessment 523.7 Management 543.8 Treatment 543.9 Conclusion 55References 554 Importance of Debriding and Wound Cleansing Agents in Wound Healing 59Gwendolyn Cazander, Bianca K. den Ottelander, Sandra Kamga, Martijn C.H.A. Doomen, Tim H.C. Damen and Anne Marie E. van Well4.1 What is Debridement? 594.2 The History of Debridement 594.3 Why Undertake Debridement? 604.4 Debridement Techniques and Wound Cleansing Agents 624.4.1 Mechanical Debridement 624.4.2 Biological Debridement 724.4.3 Enzymatic Debridement 744.4.4 Autolytic Debridement 774.4.5 Wound Cleansing 794.4.6 Other Debridement Therapies 804.5 What is the Future of Debridement? 81References 825 Treatment of Mixed Infections in Wounds 91Asif Ahmed and Joshua Boateng5.1 Introduction 915.1.1 Wound Healing Process 925.1.2 Types of Chronic Wounds 925.2 Prevalence of Mixed Infections 945.2.1 Bacterial–Fungal Interactions 955.2.2 Bacterial–Bacterial Interactions 985.2.3 Host Responses to Mixed Infections and Drug Resistance 995.3 Management of Mixed Infected Wounds 1005.3.1 Clinical and Microbiological Diagnosis 1015.3.2 Debridement and Cleansing 1015.3.3 Antimicrobial Therapies 1025.3.4 Hyperbaric Oxygen Therapy 1045.3.5 Phage Therapy 1045.4 Summary and Future Perspectives 104References 1056 Treatment of Biofilms in Infected Wounds 115Philip Debrah, Awo Afi Kwapong and Mansa Fredua-Agyeman6.1 Introduction 1156.2 Why and How Biofilms Form 1166.3 Wound Biofilms 1186.3.1 Wound Healing 1196.4 Biofilms and Wounds 1196.4.1 Simulation of Biofilms in Wounds 1206.5 Treatment of Biofilms in Wounds 1266.5.1 Biofilm Eradication 1266.5.2 Current Treatment Protocols 1286.6 Clinical Examples 1286.7 Summary 128References 1307 Freeze-Dried Wafers for Wound Healing 137Shiow-Fern Ng7.1 Introduction 1377.2 Wafer as a Modern Wound Dressing 1387.3 Freeze-Drying Process 1397.4 Wafer Preparation 1407.5 Wafer Assessments 1417.5.1 Morphology 1427.5.2 Swelling Index 1447.5.3 Mechanical Properties 1457.5.4 In Vitro Drug Release 1457.5.5 Cell Viability 1467.6 Wafer Biopolymers 1467.6.1 Alginate 1477.6.2 Chitosan 1487.6.3 Carboxymethylcellulose 1497.7 Conclusion 150References 1508 Silver and Silver Nanoparticle-Based Antimicrobial Dressings 157Joshua Boateng and Ovidio Catanzano8.1 Introduction 1578.1.1 Brief History of Silver as an Antibiotic 1598.1.2 Mechanism of Action 1608.1.3 Bacterial Resistance to Silver 1648.2 Silver Dressings in Wound Healing 1678.2.1 Silver-Based Antimicrobial Dressings 1698.2.2 Silver Nanoparticle-Based Antimicrobial Dressings 1708.3 Cost-Effectiveness of Silver Dressings 1758.4 Concluding Remarks 176References 1779 Hydrogel Dressings 185Galiya S. Irmukhametova, Grigoriy A. Mun and Vitaliy V. Khutoryanskiy9.1 Introduction 1859.1.1 Classification by Origin of Materials Used to Prepare Hydrogels 1869.1.2 Classification by Composition and Structure of Hydrogels 1869.1.3 Classification by the Type of Cross-Linking 1879.1.4 Classification Based on the Shape and Dimensions of Hydrogels 1879.1.5 Classification Based on the Charge of Macromolecules Forming Hydrogels 1879.1.6 Classification Based on Functional Properties of the Hydrogels 1879.2 Mechanism of Hydrogel Swelling 1879.2.1 Swelling of Temperature-Sensitive Hydrogels and Their Application in Wound Healing 1899.2.2 Swelling of Light-Sensitive Hydrogels 1909.2.3 Swelling of Electro-Sensitive Hydrogels 1919.3 Application of Hydrogels as Wound Dressings 1919.4 Industrial Methods for the Synthesis of Hydrogels for Wound Dressings 1939.4.1 Polymerization Methods 1939.4.2 Cross-Linking of Polymers 1959.5 Antimicrobial Hydrogels with Special Additives 1989.6 Conclusion 200Acknowledgments 201References 20110 Gene Therapy for the Treatment of Chronic Wounds 209Marcos Garcia-Fuentes10.1 Introduction 20910.2 Pharmacodynamics of Gene Therapy in Chronic Wounds 21010.2.1 Signalling Supplementation 21010.2.2 Pathway Inhibition 21110.3 Administration Routes and Methods 21210.3.1 Systemic Delivery 21210.3.2 Topical Delivery 21210.3.3 Intralesional Delivery 21310.4 Gene Delivery Systems 21310.4.1 Physical Methods 21410.4.2 Viral Vectors 21510.4.3 Chemical Delivery Systems 21710.4.4 Gene-Activated Matrices 22010.5 Clinical Evaluation 22110.6 Conclusion 226Acknowledgements 226References 22711 Honey in Wound Healing 235Emi Maruhashi11.1 The History of Honey 23511.2 Composition 23611.3 Honey Research 23611.4 Medical Grade Honey 23711.5 Modes of Action 23811.6 Applications and Specific Wound Types 24211.7 Practical Considerations 24611.8 Novel Concepts and Conclusions 247References 24812 Regeneration Using Tissue Engineered Skin Strategies 255Lucília P. da Silva, Mariana T. Cerqueira and Alexandra P. Marques12.1 Introduction 25512.2 Skin Physiology and Wounding 25612.3 Skin Tissue Engineering 25812.4 Evolving Skin Tissue Engineering Strategies 25912.4.1 Balancing the Inflammatory Phase 26112.4.2 Enhancement of Re-Epithelialization 26312.4.3 Target of Dermal Matrix Synthesis and Remodeling 26912.4.4 Re-Establishment of the Vascular Network 27012.4.5 Innervation Shaping 28012.4.6 Appendages and Pigmentation 28112.5 Conclusion 282References 28313 Local Delivery of Growth Factors Using Wound Dressings 291Ovidio Catanzano and Joshua Boateng13.1 Wound Dressings as Delivery Platforms for Growth Factors 29113.2 Growth Factors Involved in the Wound Healing Process 29213.3 Local Delivery of Growth Factors Using Wound Dressings 29613.4 Integration of Platelet-Rich Plasma in Wound Dressings 29913.5 Enhancing Local Growth Factor Expression Using Gene Therapy 30013.6 Wound Delivery of Growth Factors from Living Systems 30213.7 Regulatory Considerations 30513.8 Conclusions and Future Perspectives 306References 30714 Electrospinning Technologies in Wound Dressing Applications 315Giuseppina Sandri, Silvia Rossi, Maria Cristina Bonferoni, Carla Caramella and Franca Ferrari14.1 Introduction 31514.2 Basic Concept and Electrospinning Set-Up 31614.3 Parameters Affecting the Electrospinning Process 31814.4 Process Parameters 31914.4.1 Electric Field Strength 31914.4.2 Flow Rate 31914.4.3 Needle-to-Collector Distance 32014.4.4 Collector and Needle Types 32014.5 Solution Parameters 32114.5.1 Molecular Weight and Polymer Concentration 32114.5.2 Surface Tension 32214.5.3 Conductivity/Surface Charge Density 32214.5.4 Environmental Parameters 32214.6 Biomedical Applications of Nanofibrous Membranes 32314.6.1 Wound Dressings and Wound Healing 32314.6.2 Electrospun Dressings 32514.7 Chemicophysical and Biopharmaceutical Characterizations 32514.8 Dressing/Scaffold Parameters Affecting Cell Functions 32714.9 Materials for Fabricating Nanofibers 32814.9.1 Biopolymers 32814.10 Concluding Remarks 333References 33315 The Place of Biomaterials in Wound Healing 337Annalisa Bianchera, Ovidio Catanzano, Joshua Boateng and Lisa Elviri15.1 Introduction to Biomaterials for Wound Healing 33715.1.1 Definition of Biomaterials 33715.1.2 Functional Requirements of Wound Repair Biomaterials 33815.1.3 Classification of Biomaterials Commonly Used in Wound Healing 33815.2 Synthetic Biomaterials for Wound Healing 33915.2.1 Polyurethanes and their Derivatives 34015.2.2 Poly l-Lactic Acid 34015.2.3 Poly(Ethylene Glycol) 34115.2.4 Polycaprolactone 34115.2.5 Poly(Glycolic Acid) and Poly(Lactic-co-Glycolic Acid) 34215.3 Natural Biomaterials for Wound Healing 34315.3.1 Polysaccharide-Based Biomaterials 34315.3.2 Protein-Based Biomaterials 34815.4 Application of Biomaterials in Wound Healing 35015.4.1 Traditional and Impregnated Dressings 35015.4.2 Hydrogels 35215.4.3 Film Dressings 35315.4.4 Foam Dressings 35415.4.5 Nanofiber-Based Dressings 35515.4.6 Three-Dimensional Printed Dressings 35615.5 New Trends in Biomaterials for Wound Healing 35715.5.1 Extracellular Matrix-Derived Biomaterials 35715.5.2 Tissue Engineered Skin Substitutes 35715.6 Conclusions and Future Perspectives 358References 35916 Wound Dressings and Pressure Ulcers 367Michael Clark16.1 Overview 36716.2 Introduction to Pressure Ulcers 36716.3 The Impact of Pressure Ulcers 36916.4 Managing Pressure Ulcers 37016.5 Wound Dressings in Pressure Ulcer Treatment 37116.6 Pressure Ulcer Prevention and Wound Dressings 37716.6.1 Pressure Ulcers at the Nose 37816.6.2 Pressure Ulcers at the Heel 37816.6.3 Pressure Ulcers at the Sacrum 37816.7 Conclusions 380References 38017 3D Printed Scaffolds for Wound Healing and Tissue Regeneration 385Atabak Ghanizadeh Tabriz, Dennis Douroumis and Joshua Boateng17.1 Introduction 38517.2 3D Printing 38617.3 Laser-Based Bioprinting 38717.4 Jet-Based Printing 38917.5 Extrusion-Based Printing 39117.6 Hybrid Printing 39317.7 Conclusions 395References 395Index 399

Edited by Joshua Boateng received his Ph.D. in Pharmaceutical Sciences (Drug Delivery and Formulation) at the University of Strathclyde, Glasgow, under a Pfizer-sponsored project to develop novel formulations for wound healing applications. He has authored more than 70 peer-reviewed scientific publications and is on the Editorial Board of 3 international scientific journals, including the Journal of Pharmaceutical Sciences. He won the 2009 University of Greenwich Early Career Research Award and has reviewed for more than 60 international scientific journals. He is currently a Reader (Associate Professor) in Pharmaceutical Science and Formulation Technologies at the University of Greenwich.

• List of Contributors xiiiSeries Preface xviiPreface xix1 Chronic Wound Healing: Molecular and Biochemical Basis 1Sophia Tate and Keith Harding1.1 Introduction 11.2 Acute Wound Healing 11.3 Categories of Chronic Wound 31.3.1 Pressure Ulcers 31.3.2 Venous Stasis Ulcers 41.3.3 Ischaemic Ulcers 41.3.4 Diabetic Foot Ulcers 41.4 How a Chronic Wound Develops: Intrinsic Components 41.4.1 Cell Phenotype 51.4.2 Immune Cells and Inflammatory Mediators 61.4.3 Reactive Oxygen Species 81.4.4 Growth Factors 81.4.5 The Role of Matrix Metalloproteinases 121.5 How a Chronic Wound Develops: Extrinsic Factors 131.5.1 Infection 131.5.2 Nutrition 131.5.3 Tobacco Smoking 141.5.4 Hypoxia and Ischaemia–Reperfusion Injury 151.6 Concluding Remarks 15References 162 Clinical Perspectives for Treating Chronic Wounds 21Barun Majumder, Kirstie Lane, Diane Beck, Sandeep Singh and Duniya Majumder2.1 Background 212.2 Aetiology of Diabetic Foot Ulcers 222.3 Standard of Care for Treatment of Diabetic Foot Ulcers 222.4 Commonly Used Wound Dressings for Diabetic Foot Ulcers and Their Mechanism of Action 222.5 Absorbent and Superabsorbent Dressings 232.6 Alginates 232.7 Films 232.8 Foams 242.9 Honeys 242.10 Hydrogels 252.11 The Role of a Split Thickness Skin Graft in Diabetic Foot Ulcers 252.12 Negative Pressure Wound Therapy 252.13 Larval Therapy 272.14 Clinical Case Studies from Multidisciplinary Diabetic Foot Clinic 272.14.1 Neuropathic Wound 272.14.2 Ischaemic Wound 292.14.3 Neuro-Ischaemic Wound 312.14.4 Osteomyelitis 332.14.5 Charcot’s Foot 352.14.6 Necrotising Fasciitis in a Patient with Diabetes 362.15 Summary 39Acknowledgements 39References 393 Prediction, Prevention, Assessment, and Management of Skin Tears in the Aging Population 43Kimberly LeBlanc and Karen Campbell3.1 Introduction 433.2 Skin Tear Prevalence and Incidence 443.3 Predicting Skin Tears 453.4 Prevention 473.5 ISTAP Risk Reduction Program 493.5.1 General Health 493.5.2 Mobility 503.5.3 Skin 513.6 Assessment 523.7 Management 543.8 Treatment 543.9 Conclusion 55References 554 Importance of Debriding and Wound Cleansing Agents in Wound Healing 59Gwendolyn Cazander, Bianca K. den Ottelander, Sandra Kamga, Martijn C.H.A. Doomen, Tim H.C. Damen and Anne Marie E. van Well4.1 What is Debridement? 594.2 The History of Debridement 594.3 Why Undertake Debridement? 604.4 Debridement Techniques and Wound Cleansing Agents 624.4.1 Mechanical Debridement 624.4.2 Biological Debridement 724.4.3 Enzymatic Debridement 744.4.4 Autolytic Debridement 774.4.5 Wound Cleansing 794.4.6 Other Debridement Therapies 804.5 What is the Future of Debridement? 81References 825 Treatment of Mixed Infections in Wounds 91Asif Ahmed and Joshua Boateng5.1 Introduction 915.1.1 Wound Healing Process 925.1.2 Types of Chronic Wounds 925.2 Prevalence of Mixed Infections 945.2.1 Bacterial–Fungal Interactions 955.2.2 Bacterial–Bacterial Interactions 985.2.3 Host Responses to Mixed Infections and Drug Resistance 995.3 Management of Mixed Infected Wounds 1005.3.1 Clinical and Microbiological Diagnosis 1015.3.2 Debridement and Cleansing 1015.3.3 Antimicrobial Therapies 1025.3.4 Hyperbaric Oxygen Therapy 1045.3.5 Phage Therapy 1045.4 Summary and Future Perspectives 104References 1056 Treatment of Biofilms in Infected Wounds 115Philip Debrah, Awo Afi Kwapong and Mansa Fredua-Agyeman6.1 Introduction 1156.2 Why and How Biofilms Form 1166.3 Wound Biofilms 1186.3.1 Wound Healing 1196.4 Biofilms and Wounds 1196.4.1 Simulation of Biofilms in Wounds 1206.5 Treatment of Biofilms in Wounds 1266.5.1 Biofilm Eradication 1266.5.2 Current Treatment Protocols 1286.6 Clinical Examples 1286.7 Summary 128References 1307 Freeze-Dried Wafers for Wound Healing 137Shiow-Fern Ng7.1 Introduction 1377.2 Wafer as a Modern Wound Dressing 1387.3 Freeze-Drying Process 1397.4 Wafer Preparation 1407.5 Wafer Assessments 1417.5.1 Morphology 1427.5.2 Swelling Index 1447.5.3 Mechanical Properties 1457.5.4 In Vitro Drug Release 1457.5.5 Cell Viability 1467.6 Wafer Biopolymers 1467.6.1 Alginate 1477.6.2 Chitosan 1487.6.3 Carboxymethylcellulose 1497.7 Conclusion 150References 1508 Silver and Silver Nanoparticle-Based Antimicrobial Dressings 157Joshua Boateng and Ovidio Catanzano8.1 Introduction 1578.1.1 Brief History of Silver as an Antibiotic 1598.1.2 Mechanism of Action 1608.1.3 Bacterial Resistance to Silver 1648.2 Silver Dressings in Wound Healing 1678.2.1 Silver-Based Antimicrobial Dressings 1698.2.2 Silver Nanoparticle-Based Antimicrobial Dressings 1708.3 Cost-Effectiveness of Silver Dressings 1758.4 Concluding Remarks 176References 1779 Hydrogel Dressings 185Galiya S. Irmukhametova, Grigoriy A. Mun and Vitaliy V. Khutoryanskiy9.1 Introduction 1859.1.1 Classification by Origin of Materials Used to Prepare Hydrogels 1869.1.2 Classification by Composition and Structure of Hydrogels 1869.1.3 Classification by the Type of Cross-Linking 1879.1.4 Classification Based on the Shape and Dimensions of Hydrogels 1879.1.5 Classification Based on the Charge of Macromolecules Forming Hydrogels 1879.1.6 Classification Based on Functional Properties of the Hydrogels 1879.2 Mechanism of Hydrogel Swelling 1879.2.1 Swelling of Temperature-Sensitive Hydrogels and Their Application in Wound Healing 1899.2.2 Swelling of Light-Sensitive Hydrogels 1909.2.3 Swelling of Electro-Sensitive Hydrogels 1919.3 Application of Hydrogels as Wound Dressings 1919.4 Industrial Methods for the Synthesis of Hydrogels for Wound Dressings 1939.4.1 Polymerization Methods 1939.4.2 Cross-Linking of Polymers 1959.5 Antimicrobial Hydrogels with Special Additives 1989.6 Conclusion 200Acknowledgments 201References 20110 Gene Therapy for the Treatment of Chronic Wounds 209Marcos Garcia-Fuentes10.1 Introduction 20910.2 Pharmacodynamics of Gene Therapy in Chronic Wounds 21010.2.1 Signalling Supplementation 21010.2.2 Pathway Inhibition 21110.3 Administration Routes and Methods 21210.3.1 Systemic Delivery 21210.3.2 Topical Delivery 21210.3.3 Intralesional Delivery 21310.4 Gene Delivery Systems 21310.4.1 Physical Methods 21410.4.2 Viral Vectors 21510.4.3 Chemical Delivery Systems 21710.4.4 Gene-Activated Matrices 22010.5 Clinical Evaluation 22110.6 Conclusion 226Acknowledgements 226References 22711 Honey in Wound Healing 235Emi Maruhashi11.1 The History of Honey 23511.2 Composition 23611.3 Honey Research 23611.4 Medical Grade Honey 23711.5 Modes of Action 23811.6 Applications and Specific Wound Types 24211.7 Practical Considerations 24611.8 Novel Concepts and Conclusions 247References 24812 Regeneration Using Tissue Engineered Skin Strategies 255Lucília P. da Silva, Mariana T. Cerqueira and Alexandra P. Marques12.1 Introduction 25512.2 Skin Physiology and Wounding 25612.3 Skin Tissue Engineering 25812.4 Evolving Skin Tissue Engineering Strategies 25912.4.1 Balancing the Inflammatory Phase 26112.4.2 Enhancement of Re-Epithelialization 26312.4.3 Target of Dermal Matrix Synthesis and Remodeling 26912.4.4 Re-Establishment of the Vascular Network 27012.4.5 Innervation Shaping 28012.4.6 Appendages and Pigmentation 28112.5 Conclusion 282References 28313 Local Delivery of Growth Factors Using Wound Dressings 291Ovidio Catanzano and Joshua Boateng13.1 Wound Dressings as Delivery Platforms for Growth Factors 29113.2 Growth Factors Involved in the Wound Healing Process 29213.3 Local Delivery of Growth Factors Using Wound Dressings 29613.4 Integration of Platelet-Rich Plasma in Wound Dressings 29913.5 Enhancing Local Growth Factor Expression Using Gene Therapy 30013.6 Wound Delivery of Growth Factors from Living Systems 30213.7 Regulatory Considerations 30513.8 Conclusions and Future Perspectives 306References 30714 Electrospinning Technologies in Wound Dressing Applications 315Giuseppina Sandri, Silvia Rossi, Maria Cristina Bonferoni, Carla Caramella and Franca Ferrari14.1 Introduction 31514.2 Basic Concept and Electrospinning Set-Up 31614.3 Parameters Affecting the Electrospinning Process 31814.4 Process Parameters 31914.4.1 Electric Field Strength 31914.4.2 Flow Rate 31914.4.3 Needle-to-Collector Distance 32014.4.4 Collector and Needle Types 32014.5 Solution Parameters 32114.5.1 Molecular Weight and Polymer Concentration 32114.5.2 Surface Tension 32214.5.3 Conductivity/Surface Charge Density 32214.5.4 Environmental Parameters 32214.6 Biomedical Applications of Nanofibrous Membranes 32314.6.1 Wound Dressings and Wound Healing 32314.6.2 Electrospun Dressings 32514.7 Chemicophysical and Biopharmaceutical Characterizations 32514.8 Dressing/Scaffold Parameters Affecting Cell Functions 32714.9 Materials for Fabricating Nanofibers 32814.9.1 Biopolymers 32814.10 Concluding Remarks 333References 33315 The Place of Biomaterials in Wound Healing 337Annalisa Bianchera, Ovidio Catanzano, Joshua Boateng and Lisa Elviri15.1 Introduction to Biomaterials for Wound Healing 33715.1.1 Definition of Biomaterials 33715.1.2 Functional Requirements of Wound Repair Biomaterials 33815.1.3 Classification of Biomaterials Commonly Used in Wound Healing 33815.2 Synthetic Biomaterials for Wound Healing 33915.2.1 Polyurethanes and their Derivatives 34015.2.2 Poly l-Lactic Acid 34015.2.3 Poly(Ethylene Glycol) 34115.2.4 Polycaprolactone 34115.2.5 Poly(Glycolic Acid) and Poly(Lactic-co-Glycolic Acid) 34215.3 Natural Biomaterials for Wound Healing 34315.3.1 Polysaccharide-Based Biomaterials 34315.3.2 Protein-Based Biomaterials 34815.4 Application of Biomaterials in Wound Healing 35015.4.1 Traditional and Impregnated Dressings 35015.4.2 Hydrogels 35215.4.3 Film Dressings 35315.4.4 Foam Dressings 35415.4.5 Nanofiber-Based Dressings 35515.4.6 Three-Dimensional Printed Dressings 35615.5 New Trends in Biomaterials for Wound Healing 35715.5.1 Extracellular Matrix-Derived Biomaterials 35715.5.2 Tissue Engineered Skin Substitutes 35715.6 Conclusions and Future Perspectives 358References 35916 Wound Dressings and Pressure Ulcers 367Michael Clark16.1 Overview 36716.2 Introduction to Pressure Ulcers 36716.3 The Impact of Pressure Ulcers 36916.4 Managing Pressure Ulcers 37016.5 Wound Dressings in Pressure Ulcer Treatment 37116.6 Pressure Ulcer Prevention and Wound Dressings 37716.6.1 Pressure Ulcers at the Nose 37816.6.2 Pressure Ulcers at the Heel 37816.6.3 Pressure Ulcers at the Sacrum 37816.7 Conclusions 380References 38017 3D Printed Scaffolds for Wound Healing and Tissue Regeneration 385Atabak Ghanizadeh Tabriz, Dennis Douroumis and Joshua Boateng17.1 Introduction 38517.2 3D Printing 38617.3 Laser-Based Bioprinting 38717.4 Jet-Based Printing 38917.5 Extrusion-Based Printing 39117.6 Hybrid Printing 39317.7 Conclusions 395References 395Index 399