Foreword xvii
1 Skin Structure and Biology 1
Wei-Meng Woo
1.1 Introduction 1
1.2 Skin Structure 2
1.2.1 Overview of Skin Tissue Organization 2
1.2.2 Epidermis 3
1.2.3 Dermis 6
1.2.4 Hypodermis 7
1.2.5 Skin Appendages 8
1.3 Skin Biology 9
1.3.1 Homeostasis: Epidermal Self-renewal 9
1.3.2 Formation of aWater Barrier 10
1.3.3 Getting Across theWater Barrier 11
References 12
2 Wound Healing and Its Imaging 15
Jiah Shin Chin, Leigh Madden, Sing Yian Chew, Anthony R.J. Phillips and David L. Becker
2.1 Hemostasis and Essential Inflammation 15
2.2 Re-epithelialization 18
2.3 Granulation Tissue Formation 19
2.4 Scar Tissue Formation 20
2.5 Imaging of Wound Healing 21
2.6 Macroscopic Digital Imaging for Wound Size 22
2.7 Hyperspectral and Multispectral Imaging 22
2.8 Near-Infrared Spectroscopy 23
2.9 Raman Imaging 23
2.10 Confocal Microscopy 24
2.11 Multiphoton Imaging and Second Harmonics 24
References 27
3 Common Skin Diseases: Chronic Inflammatory and Autoimmune Disorders 35
Navin Kumar Verma, Maurice Adrianus Monique van Steensel, Praseetha Prasannan, Zhi Sheng Poh, Alan D. Irvine and Hazel H. Oon
3.1 Introduction 35
3.2 Psoriasis 36
3.2.1 Definition and Prevalence 36
3.2.2 Clinical Features, Pathogenesis, and Pathophysiology 37
3.2.3 Diagnosis 39
3.2.4 Therapy 40
3.3 Atopic Dermatitis (AD) 40
3.3.1 Definition and Prevalence 40
3.3.2 Clinical Features, Pathogenesis, and Pathophysiology 41
3.3.3 Diagnosis 42
3.3.4 Therapy 43
3.4 Scleroderma 43
3.4.1 Definition and Prevalence 43
3.4.2 Clinical Features, Pathogenesis, and Pathophysiology 44
3.4.3 Diagnosis 44
3.4.4 Therapy 45
3.5 Dermatomyositis (DM) 45
3.5.1 Definition and Prevalence 45
3.5.2 Clinical Features, Pathogenesis, and Pathophysiology 46
3.5.3 Diagnosis 46
3.5.4 Therapy 47
3.6 Cutaneous Lupus Erythematosus (CLE) 47
3.6.1 Definition and Prevalence 47
3.6.2 Clinical Features, Pathogenesis, and Pathophysiology 47
3.6.3 Diagnosis 48
3.6.4 Treatment 49
3.7 Generalized Vitiligo (GV) 49
3.7.1 Definition and Prevalence 49
3.7.2 Clinical Features, Pathogenesis, and Pathophysiology 49
3.7.3 Diagnosis 50
3.7.4 Treatment 51
3.8 Concluding Remarks 51
Acknowledgments 51
References 52
4 Common Skin Diseases: Autoimmune Blistering Disorders 61
Navin Kumar Verma, Shermaine Wan Yu Low, Hazel H. Oon, Dermot Kelleher and Maurice Adrianus Monique van Steensel
4.1 Introduction 61
4.2 Pemphigus 62
4.2.1 Definition and Prevalence 62
4.2.2 Clinical Features, Pathogenesis, and Pathophysiology 62
4.2.3 Diagnosis 67
4.2.4 Treatment 67
4.3 Pemphigoid 68
4.3.1 Definition and Prevalence 68
4.3.2 Clinical Features, Pathogenesis, and Pathophysiology 68
4.3.3 Diagnosis 70
4.3.4 Treatment 70
4.4 Dermatitis Herpetiformis (DH) 70
4.4.1 Definition and Prevalence 70
4.4.2 Clinical Features, Pathogenesis, and Pathophysiology 71
4.4.3 Diagnosis 71
4.4.4 Treatment 71
4.5 Epidermolysis Bullosa Acquisita (EBA) 72
4.5.1 Definition and Prevalence 72
4.5.2 Clinical Features, Pathogenesis, and Pathophysiology 72
4.5.3 Diagnosis 73
4.5.4 Treatment 73
4.6 Concluding Remarks and Future Directions 73
Acknowledgments 74
References 74
5 Common Skin Diseases: Skin Cancer 83
Tuyen T.L. Nguyen, Eric Tarapore and Scott X. Atwood
5.1 Introduction 83
5.2 Basal Cell Carcinoma 83
5.2.1 Risk Factors 84
5.2.2 Classification 85
5.2.3 Cell of Origin 85
5.2.4 Signaling Pathways 86
5.2.5 Common Treatments 87
5.3 Squamous Cell Carcinoma 88
5.3.1 Risk Factors 89
5.3.2 Classification 89
5.3.3 Cell of Origin 90
5.3.4 Signaling Pathways 90
5.3.5 Common Treatments 91
5.4 Melanoma 92
5.4.1 Risk Factors 92
5.4.2 Classification 93
5.4.3 Cell of Origin 94
5.4.4 Signaling Pathways 94
5.4.5 Common Treatments 94
5.5 Concluding Remarks 95
References 96
6 Preclinical Models for Drug Screening and Target Validation 105
Ivo J.H.M. de Vos, Julia Verbist and Maurice A.M. van Steensel
6.1 Introduction 105
6.2 Ex Vivo Models of Human Skin 105
6.2.1 Introduction 105
6.2.2 Ex Vivo Models of Skin Barrier Function and Dermal Absorption 107
6.2.3 Ex Vivo Models of Cutaneous Wound Healing 107
6.2.4 Ex Vivo Hair Follicle Culture 108
6.3 In Vitro Models of Human Skin 108
6.3.1 Introduction 108
6.3.2 Two-Dimensional Cell Culture Models 109
6.3.3 Three-Dimensional Reconstructed Human Skin Models 109
6.4 In Vivo Animal Models 112
6.4.1 Caenorhabditis elegans 112
6.4.2 Drosophila melanogaster 113
6.4.3 Danio rerio 116
6.4.4 Mus musculus 118
6.4.5 Cavia porcellus 122
6.4.6 Oryctolagus cuniculus 124
6.4.7 Canis lupus familiaris 126
6.4.8 Sus scrofa domesticus 128
References 129
7 Skin Tissue Engineering with Nanostructured Materials 147
Zahra Davoudi and Qun Wang
7.1 Introduction 147
7.2 Nanostructured Materials for Skin Tissue Engineering 148
7.2.1 Natural Biomaterials for Skin Tissue Engineering 148
7.2.2 Synthetic Polymers for Skin Tissue Engineering 152
7.2.3 Blend of Natural and Synthetic Materials 153
7.3 Fabrication Techniques 154
7.3.1 Self-Assembly and Phase Separation 154
7.3.2 Electrospinning 156
7.4 Clinical Application of Tissue Engineered Skin 157
7.4.1 Skin Grafts 157
7.4.2 Stem Cell Application in Skin Tissue Engineering 159
7.5 Summary 162
References 163
8 Topical and Transdermal Delivery with Chemical Enhancers and Nanoparticles 169
Chandrashekhar Voshavar, Praveen Kumar Vemula and Srujan Marepally
8.1 Introduction 169
8.2 Anatomy of Skin/Skin Structure 170
8.3 Skin Permeation Routes 171
8.4 Chemical Enhancers (CEs) or Skin Penetration Enhancers 172
8.4.1 Characteristics of an Ideal Chemical Enhancer 173
8.4.2 Classification of Chemical Enhancers 173
8.5 Transdermal Delivery Using Nanoparticles 182
8.5.1 Lipid Based Nanoparticles 184
8.5.2 Polymer Based Nanoparticles 185
8.6 Peptides for Skin Permeation 189
8.7 Peptide-Nucleic Acid Nanoconjugates 190
8.8 Spherical Nucleic Acids 191
8.9 Conclusion 191
References 192
9 Needle-Free Jet Injectors for Dermal and Transdermal Delivery of Actives 201
Michele Schlich, Rosita Primavera, Francesco Lai, Chiara Sinico and Paolo Decuzzi
9.1 Introduction 201
9.2 Components and Functioning Principle 203
9.3 Modulating the Depth of Active Delivery 203
9.4 Clinical and Preclinical Use of Needle-Free Jet Injectors for Systemic Drug Delivery 206
9.4.1 Vaccines 206
9.4.2 Insulin 208
9.4.3 Growth Hormone 210
9.4.4 Triptans 211
9.4.5 Others 211
9.5 Clinical and Preclinical Use of Needle-Free Jet Injectors for Local Drug Delivery 212
9.5.1 Local Anesthetics 212
9.5.2 Others 213
9.6 Future Perspectives: Jet Injection for Nano-/Microparticles 215
References 216
10 Microneedles for Transdermal Drug Delivery 223
Eman M. Migdadi and Ryan F. Donnelly
10.1 Introduction 223
10.2 Microneedles 223
10.2.1 MN Delivery Strategies 225
10.2.2 MN Fabrication Methods 232
10.2.3 MNs and Vaccine Delivery 235
10.2.4 MNs for Patient Drug Monitoring 237
10.2.5 MN Skin Insertion and Recovery Process 239
10.2.6 Pain Perception and Skin Adverse Reactions of MN Application 242
10.2.7 MN Products 243
10.2.8 Combination of MNs with Other Techniques 245
10.2.9 MN-Assisted Microparticle and Nanoparticle Permeation 245
10.3 Microneedles in Management of Skin Disorders 247
10.4 Future Considerations for MN Technology 249
10.5 Conclusion 250
References 251
11 Ultrasound-Enhanced Transdermal Drug Delivery 271
James Jing Kwan and Sunali Bhatnagar
11.1 Introduction 271
11.2 Principles in Ultrasound 271
11.2.1 Acoustic Waves 271
11.2.2 Ultrasound Transducers and Instrumentation 272
11.2.3 Propagation of Ultrasound 274
11.2.4 Ultrasound Phenomena 274
11.2.5 Mechanisms of Action 276
11.3 State of the Art in Ultrasound-Enhanced Transdermal Drug Delivery 277
11.3.1 Modes of Delivery 277
11.3.2 Drug Dosage Medium 279
11.3.3 Ultrasound-Assisted Drug Delivery: Drug Formulations and Safety Concerns 280
11.3.4 Applications of Ultrasound-Enhanced Transdermal Delivery 283
11.4 Conclusions 284
References 284
12 Iontophoresis Enhanced Transdermal Drug Delivery 291
Xiayu Ning, Razina Z. Seeni and Chenjie Xu
12.1 Introduction 291
12.1.1 Hyperhidrosis 292
12.1.2 Delivery of Anesthetics for Pain Management 292
12.1.3 Diagnosis of Cystic Fibrosis 292
12.1.4 Glucose Monitoring 293
12.1.5 Growing Interest 293
12.2 Enhancing Transdermal Drug Delivery Using Iontophoresis Alone 294
12.2.1 Iontophoretic Transdermal Delivery of Small Molecules 297
12.2.2 Iontophoretic Transdermal Delivery of Macromolecules 297
12.3 Enhancing Transdermal Drug Delivery Using Combination of Iontophoresis and Other Approaches 300
12.3.1 Iontophoresis with Chemical Enhancers 300
12.3.2 Iontophoresis with Microneedles 302
12.3.3 Iontophoresis and Nanoparticles 303
12.4 Summary and Outlook 304
References 304
13 Ultrasound Imaging in Dermatology 309
Jihun Kim, Sangyeon Youn and Jae Youn Hwang
13.1 Introduction 309
13.2 The Physics of Ultrasound 309
13.3 Ultrasonic Transducers 313
13.3.1 Piezoelectric Materials 314
13.3.2 Matching Layer 317
13.3.3 Backing Layer 317
13.3.4 Single-Element Ultrasound Transducers 318
13.3.5 Array Ultrasound Transducers 318
13.4 Ultrasound Imaging Systems for Skin Diagnosis 320
13.4.1 Ultrasound Imaging with Single-Element Ultrasound Transducers 321
13.4.2 Ultrasound Imaging with Array Ultrasound Transducers 326
13.5 Applications of Ultrasound Imaging in Dermatology 330
13.5.1 Ultrasound Imaging of Skin Cancer 330
13.5.2 Ultrasound Imaging of Inflammatory and Infectious Skin Diseases 332
13.5.3 Ultrasound Imaging for Other Skin Applications 334
13.6 Conclusions 334
Acknowledgments 335
References 335
14 Quantitative Magnetic Resonance Imaging of the Skin: In Vitro and In Vivo Applications 341
Bernard Querleux, Genevieve Guillot, Jean-Christophe Ginefri, Marie Poirier-Quinot and Luc Darrasse
14.1 Introduction 341
14.2 Clinical Magnetic Resonance Imaging of the Skin 342
14.2.1 Hardware Challenges for Skin Imaging 342
14.2.2 State of the Art of Clinical MR Applications of Healthy and Diseased Skin 348
14.2.3 MR Imaging of the Skin on the Face 349
14.2.4 Water States in Skin by Quantitative MR Imaging 350
14.3 Quantitative MR Imaging of the Skin In Vitro 351
14.3.1 Opportunities with Preclinical MR Systems 351
14.3.2 State of the Art of In Vitro MR Applications 352
14.3.3 Quantification of Water States in Reconstructed Skin 354
14.4 Conclusion and Perspectives 359
References 360
15 High-Resolution Optical Coherence Tomography (OCT) for Skin Imaging 371
Xiaojun Yu, XianghongWang, LuluWang, Razina Z. Seeni and Linbo Liu
15.1 Introduction 371
15.2 HR-OCT Systems for Skin Imaging 373
15.2.1 TD-OCT Systems 373
15.2.2 FD-OCT Systems 375
15.2.3 PS-OCT 381
15.3 Skin Imaging with HR-OCT 382
15.3.1 Normal Skin Imaging Applications 382
15.3.2 Skin Imaging in Clinical Practice 387
15.3.3 Skin Imaging for Laboratory Research 388
15.4 Discussions 398
15.5 Conclusion 400
Acknowledgments 400
References 400
16 Photoacoustic Imaging of Skin 411
Emelina Vienneau, Tri Vu and Junjie Yao
16.1 Introduction 411
16.2 Photoacoustic Imaging Technology 412
16.3 Applications to Skin Imaging 414
16.3.1 Skin Cancers 414
16.3.2 Tumor Environment Analysis 418
16.3.3 Detection of Noncancerous Skin Diseases 422
16.3.4 Burn Injury Assessment and Monitoring of Healing 423
16.3.5 Monitoring Glucose Levels 425
16.3.6 Other Molecular Applications in Skin Imaging 426
16.4 Outlook 428
References 429
17 Laser Speckle Techniques for Flow Monitoring in Skin 443
Renzhe Bi, Malini Olivo and Kijoon Lee
17.1 Introduction 443
17.2 Laser Speckle Contrast Imaging 444
17.2.1 Working Principle of Laser Speckle Contrast Imaging 444
17.2.2 Applications of LSCI 446
17.3 Diffuse Speckle Contrast Analysis 448
17.3.1 Theory of Diffuse Speckle Contrast Analysis 449
17.3.2 Deep Tissue Blood Flow and Cold-Induced Vasodilation 451
17.4 Diffuse Speckle Tomography 456
17.4.1 Depth Sensitivity of Flow Measurement 456
17.4.2 Tomographic Flow Imaging 458
17.5 The Future of Diffuse Speckle Analysis and Imaging 459
References 460
Index 465
