简介
Musculoskeletal applications of tissue engineering will be among the first to achieve widespread clinical use, and the resulting shift in clinical and surgical paradigms will highlight the need for an authoritative text on tissue engineering for musculoskeletal tissues including nerve, bone, tendon, skin, vessels, and cartilage. This book will serve the needs of a large readership including plastic surgeons, orthopedic surgeons, medical residents and medical students, researchers and academic faculty in regenerative medicine and biomedical engineering, and medical device experts. This textbook will serve as the curriculum for undergraduate and graduate courses in biomedical engineering and surgery. Notable contributors to this volume include Antonios G Mikos, PhD; Wei Liu, MD; Yilin Cao, MD; Mark Randolph, MAS; Jennifer Elisseeff, PhD; Geoffrey C Gurtner, MD; Michael T Longaker, MD; and James Chang, MD, all of whom are leaders in tissue engineering research and applications.
目录
Contents 8
Acknowledgments 6
Contributors 10
Chapter 1 Tissue Engineering: A Historical Perspective James D. Kretlow and Antonios G. Mikos 14
Introduction 14
Defining tissue engineering 14
Overview: Why tissue engineering? 15
Conception to Birth 15
Ancient foundations 16
Renaissance through 19th century 17
20th century advances 18
Organ transplantation 19
Vascular grafts 20
Bone and osteoinduction 20
Stem cells 20
Other cell-based approaches 20
The birth of tissue engineering 21
The 1990s: Research, recognition, and general interest 21
Growth: The 21st Century 22
Continued advancement 22
The Future and the Past 24
Conclusions 25
References 25
Chapter 2 Current Clinical Needs in Hand Surgery L. Scott Levin 30
References 31
Chapter 3 Principles of Tissue Engineering for Reconstruction of the Hand Ryosuke Kakinoki 34
Preface 34
Tissue Engineering 35
Cell Transplantation 35
Totipotent and pluripotent stem cells 35
ES cells 36
iPS cells 36
Adult stem cells 37
Mesenchymal stromal cells 37
Tissue Scaffolds 38
Cell Environments 38
Peripheral Nerve Engineering 39
Bone Tissue Engineering 41
Tendon Tissue Engineering 42
Cartilaginous Tissue Engineering 44
Skin Tissue Engineering 45
Small Blood Vessel Engineering 46
The Future 46
References 46
Chapter 4 Primary Cell Lines and Stem Cells Katie L. Pricola and Hermann Peter Lorenz 54
Introduction 54
Human Embryonic Stem Cells 54
Maintenance of ESCs 55
Induced Pluripotent Stem Cells (iPS Cells) 55
Adult Tissue-Derived Stem Cells 56
Mesenchymal stem cells (MSCs) 57
Defining MSCs: Isolation, identification, and selection 57
MSC Niche: The Bone Marrow (BM) microenvironment 58
In vivo and in vitro capabilities 58
MSC self-renewal 58
Immune function 59
Multilineage differentiation potential 60
Osteogenesis 60
Chondrogenesis 61
Adipogenesis 62
Tenogenesis 62
Myogenesis 63
Therapeutic potential: Immune regulation, tissue repair, and gene therapy 63
Limitations of MSCs 64
Conclusion 65
References 65
Chapter 5 Scaffolds Wei Liu and Yilin Cao 78
Introduction 78
Basic Principles 79
Natural scaffolds 80
Synthetic scaffolds 81
Recent Research in Hand Surgery 84
Scaffolds for tendon engineering 84
Scaffolds for bone and cartilage engineering 96
References 101
Chapter 6 Animal Models for Engineering Tissues in the Upper Extremity Xing Zhao and Mark A. Randolph 108
Introduction 108
Selection of an Animal Model: 110
Need for animal model 110
Suitability 110
Availability of species-specific reagents 110
Scientific and clinical relevance 111
Selection of Outcomes Measures 112
Critical Size Defects 113
Animal Models of Tissue Engineering 113
Bone 114
Animal selection, size, and macrostructure 114
Microarchitecture and composition 115
Bone remodeling and mechanical factors 116
Age and gender 116
Cartilage 117
Outcome measures 117
Species selection 118
Acute versus chronic lesions 119
Tendon and Ligament 119
Nerve 121
Species selection 121
Vessels and Vasculature 123
Species selection 124
Microcirculation 124
Muscle 125
Skin 126
Outcome measures 127
Species selection 127
The Three R\u2019s 127
References 128
Chapter 7 Guidance Strategies in Hand Tissue Engineering: Manipulating the Microenvironment Through Cellular and Material Cues Harvey Chim and Arun K. Gosain 138
Introduction 138
Cell Guidance: Inducing Site-Specific Homing of Cells Through Creation of a Biomimetic Microenvironment 139
SDF-1 伪/CXCR4 interaction in homing of mesenchymal stem cells 139
Inducing homing of cells using SDF-1 伪18 139
SDF-1 伪as an agent for cell guidance 143
Axonal Guidance as a Strategy for Nerve Tissue Engineering 144
Nerve regeneration through molecular cues, micropatterns and electromagnetic cues 144
Use of topographical cues 145
Nerve guidance channels for axon guidance 146
Vascular Guidance: Microstructural Patterning of Polymeric Scaffolds 147
Overcoming limitations of currently available scaffolds 147
Modeling the perfusion of a calvarial bone flap 148
Experimental studies into vascular guidance 148
Application of vascular guidance in hand tissue engineering 149
Guidance Strategies in Hand Tissue Engineering \u2014 Looking Forward 149
References 150
Chapter 8 Bioreactors Laurence A. Galea and Wayne A. Morrison 154
Introduction 154
Ex-vivo Bioreactors 154
In-vivo Bioreactors 156
Bioreactor Models in Tissue Engineering 158
Non specific tissue growth 159
Skin 160
Fat 160
Tendon 160
Muscle 161
Bone 161
Nerve 162
Cartilage 163
The Future 163
References 163
Chapter 9 Nerve Engineering Gregory H. Borschel 168
Rationale for Nerve Engineering 168
Ideal Characteristics of a Nerve Substitute 168
Nerve Regeneration and Special Challenges with Nerve Tissue Engineering 168
Types of nerve injury 169
Nerve regeneration and the response to nerve injury 169
Historical treatment of nerve gaps 170
Nerve engineering strategies 170
Synthetic \u201cBiodurable\u201d Conduits 170
Silicone conduits 170
Polytetrafluoroethylene (PTFE, GoreTex) conduits 171
Synthetic Biodegradable Conduits 171
Polyglycolide, Poly(DL-Lactide- 蔚-Caprolactone) and other synthetic aliphatic polyesters 171
PGA conduits 172
Poly(DL-lactide-epsilon-caprolactone) (PLCL) conduits 174
Collagen conduits 175
Tissue-based Conduits 176
Vein and arterial conduits 176
Muscle-based conduits 177
Processed and decellularized nerve allografts 177
Growth factors and cell-based based approaches 177
Conclusions 178
References 178
Chapter 10 Tendon Engineering Johan Thorfinn, Ioannis Angelidis, Brian Pridgen and James Chang 184
Introduction 184
Ultrastructure of tendon 184
Goals of tissue engineered tendon constructs 185
Principles of Tendon Tissue Engineering 186
Animal models 187
Cell Types Used for Tendon Tissue Engineering 188
Scaffold Materials 190
Polysaccharides 190
Polyesters 191
Collagen 192
Collagen derivates 192
Biological collagen scaffolds 193
Synthetic scaffolds 194
Actions to Improve Results 194
Loading 194
Molecular Enhancement 195
bFGF 195
TGF- 尾 196
PDGF 196
IGF-1 197
VEGF 197
Multi growth factor approach 198
Gene transfer 198
Future Perspectives 200
References 200
Chapter 11 Skin Deepak M. Gupta, Nicholas J. Panetta, Geoffrey C. Gurtner and Michael T. Longaker 208
Introduction 208
Skin 208
Skin of the Hand 209
Wound Healing 210
Scarless Fetal Wound Healing 211
Burden of Scarring 213
The Past: Skin Grafts and Tissue Expanders 214
The Present: Skin Substitutes 216
The Future: Molecular and Gene Therapy, and Stem Cell Biology 220
Stem Cell Biology 221
Conclusion 224
References 224
Chapter 12 Bone and Cartilage Ashley Rothenberg and Jennifer Elisseeff 232
Articular Cartilage Structure and Function 232
Bone Structure and Function 232
Natural Repair Capacity of Bone and Cartilage 233
Cartilage and Bone Development 233
Signaling in Development 235
Human Cartilage Repair Following Injury 236
Bone Tissue Repair Following Injury 236
Wound Healing and Limb Regeneration 237
Non-regenerative Tissues 239
Disease 239
Arthritis 240
Tissue Engineering of Cartilage and Bone 241
Cell Choice 241
Mesenchymal Stem Cells 242
Embryonic Stem Cells 243
Scaffolds 244
Bioactive Factors 245
Co-culture Models for Cartilage and Bone Reconstruction 246
Lingering Questions 247
References 247
Chapter 13 Blood Vessels Masayuki Yamato and Teruo Okano 256
Artery and Vein 256
The early tissue engineering of vascular grafts 256
Use of scaffolds for vascular grafts 256
Sheet-based tissue engineering 257
Capillary Networks 258
Drug delivery system (DDS) and controlled release 258
Endothelial cell transplantation 261
Microfluidics 261
Cell sheet engineering 261
Application to Hand Surgery 262
References 263
Chapter 14 Bench to Bedside: Navigating Industry, the FDA and Venture Capital Nicholas J. Panetta, Deepak M. Gupta, Michael T. Longaker and Geoffrey C. Gurtner 266
Introduction 266
Clinical Need Driven Innovation 267
Innovation in the Care of the Surgical Patient 268
Intellectual Property and the Patent Process 269
Proof of Concept 271
FDA and the Regulation of Surgical Inventions 272
Funding Acquisition 276
Commercialization 277
Summary 278
References 279
Index 282
Acknowledgments 6
Contributors 10
Chapter 1 Tissue Engineering: A Historical Perspective James D. Kretlow and Antonios G. Mikos 14
Introduction 14
Defining tissue engineering 14
Overview: Why tissue engineering? 15
Conception to Birth 15
Ancient foundations 16
Renaissance through 19th century 17
20th century advances 18
Organ transplantation 19
Vascular grafts 20
Bone and osteoinduction 20
Stem cells 20
Other cell-based approaches 20
The birth of tissue engineering 21
The 1990s: Research, recognition, and general interest 21
Growth: The 21st Century 22
Continued advancement 22
The Future and the Past 24
Conclusions 25
References 25
Chapter 2 Current Clinical Needs in Hand Surgery L. Scott Levin 30
References 31
Chapter 3 Principles of Tissue Engineering for Reconstruction of the Hand Ryosuke Kakinoki 34
Preface 34
Tissue Engineering 35
Cell Transplantation 35
Totipotent and pluripotent stem cells 35
ES cells 36
iPS cells 36
Adult stem cells 37
Mesenchymal stromal cells 37
Tissue Scaffolds 38
Cell Environments 38
Peripheral Nerve Engineering 39
Bone Tissue Engineering 41
Tendon Tissue Engineering 42
Cartilaginous Tissue Engineering 44
Skin Tissue Engineering 45
Small Blood Vessel Engineering 46
The Future 46
References 46
Chapter 4 Primary Cell Lines and Stem Cells Katie L. Pricola and Hermann Peter Lorenz 54
Introduction 54
Human Embryonic Stem Cells 54
Maintenance of ESCs 55
Induced Pluripotent Stem Cells (iPS Cells) 55
Adult Tissue-Derived Stem Cells 56
Mesenchymal stem cells (MSCs) 57
Defining MSCs: Isolation, identification, and selection 57
MSC Niche: The Bone Marrow (BM) microenvironment 58
In vivo and in vitro capabilities 58
MSC self-renewal 58
Immune function 59
Multilineage differentiation potential 60
Osteogenesis 60
Chondrogenesis 61
Adipogenesis 62
Tenogenesis 62
Myogenesis 63
Therapeutic potential: Immune regulation, tissue repair, and gene therapy 63
Limitations of MSCs 64
Conclusion 65
References 65
Chapter 5 Scaffolds Wei Liu and Yilin Cao 78
Introduction 78
Basic Principles 79
Natural scaffolds 80
Synthetic scaffolds 81
Recent Research in Hand Surgery 84
Scaffolds for tendon engineering 84
Scaffolds for bone and cartilage engineering 96
References 101
Chapter 6 Animal Models for Engineering Tissues in the Upper Extremity Xing Zhao and Mark A. Randolph 108
Introduction 108
Selection of an Animal Model: 110
Need for animal model 110
Suitability 110
Availability of species-specific reagents 110
Scientific and clinical relevance 111
Selection of Outcomes Measures 112
Critical Size Defects 113
Animal Models of Tissue Engineering 113
Bone 114
Animal selection, size, and macrostructure 114
Microarchitecture and composition 115
Bone remodeling and mechanical factors 116
Age and gender 116
Cartilage 117
Outcome measures 117
Species selection 118
Acute versus chronic lesions 119
Tendon and Ligament 119
Nerve 121
Species selection 121
Vessels and Vasculature 123
Species selection 124
Microcirculation 124
Muscle 125
Skin 126
Outcome measures 127
Species selection 127
The Three R\u2019s 127
References 128
Chapter 7 Guidance Strategies in Hand Tissue Engineering: Manipulating the Microenvironment Through Cellular and Material Cues Harvey Chim and Arun K. Gosain 138
Introduction 138
Cell Guidance: Inducing Site-Specific Homing of Cells Through Creation of a Biomimetic Microenvironment 139
SDF-1 伪/CXCR4 interaction in homing of mesenchymal stem cells 139
Inducing homing of cells using SDF-1 伪18 139
SDF-1 伪as an agent for cell guidance 143
Axonal Guidance as a Strategy for Nerve Tissue Engineering 144
Nerve regeneration through molecular cues, micropatterns and electromagnetic cues 144
Use of topographical cues 145
Nerve guidance channels for axon guidance 146
Vascular Guidance: Microstructural Patterning of Polymeric Scaffolds 147
Overcoming limitations of currently available scaffolds 147
Modeling the perfusion of a calvarial bone flap 148
Experimental studies into vascular guidance 148
Application of vascular guidance in hand tissue engineering 149
Guidance Strategies in Hand Tissue Engineering \u2014 Looking Forward 149
References 150
Chapter 8 Bioreactors Laurence A. Galea and Wayne A. Morrison 154
Introduction 154
Ex-vivo Bioreactors 154
In-vivo Bioreactors 156
Bioreactor Models in Tissue Engineering 158
Non specific tissue growth 159
Skin 160
Fat 160
Tendon 160
Muscle 161
Bone 161
Nerve 162
Cartilage 163
The Future 163
References 163
Chapter 9 Nerve Engineering Gregory H. Borschel 168
Rationale for Nerve Engineering 168
Ideal Characteristics of a Nerve Substitute 168
Nerve Regeneration and Special Challenges with Nerve Tissue Engineering 168
Types of nerve injury 169
Nerve regeneration and the response to nerve injury 169
Historical treatment of nerve gaps 170
Nerve engineering strategies 170
Synthetic \u201cBiodurable\u201d Conduits 170
Silicone conduits 170
Polytetrafluoroethylene (PTFE, GoreTex) conduits 171
Synthetic Biodegradable Conduits 171
Polyglycolide, Poly(DL-Lactide- 蔚-Caprolactone) and other synthetic aliphatic polyesters 171
PGA conduits 172
Poly(DL-lactide-epsilon-caprolactone) (PLCL) conduits 174
Collagen conduits 175
Tissue-based Conduits 176
Vein and arterial conduits 176
Muscle-based conduits 177
Processed and decellularized nerve allografts 177
Growth factors and cell-based based approaches 177
Conclusions 178
References 178
Chapter 10 Tendon Engineering Johan Thorfinn, Ioannis Angelidis, Brian Pridgen and James Chang 184
Introduction 184
Ultrastructure of tendon 184
Goals of tissue engineered tendon constructs 185
Principles of Tendon Tissue Engineering 186
Animal models 187
Cell Types Used for Tendon Tissue Engineering 188
Scaffold Materials 190
Polysaccharides 190
Polyesters 191
Collagen 192
Collagen derivates 192
Biological collagen scaffolds 193
Synthetic scaffolds 194
Actions to Improve Results 194
Loading 194
Molecular Enhancement 195
bFGF 195
TGF- 尾 196
PDGF 196
IGF-1 197
VEGF 197
Multi growth factor approach 198
Gene transfer 198
Future Perspectives 200
References 200
Chapter 11 Skin Deepak M. Gupta, Nicholas J. Panetta, Geoffrey C. Gurtner and Michael T. Longaker 208
Introduction 208
Skin 208
Skin of the Hand 209
Wound Healing 210
Scarless Fetal Wound Healing 211
Burden of Scarring 213
The Past: Skin Grafts and Tissue Expanders 214
The Present: Skin Substitutes 216
The Future: Molecular and Gene Therapy, and Stem Cell Biology 220
Stem Cell Biology 221
Conclusion 224
References 224
Chapter 12 Bone and Cartilage Ashley Rothenberg and Jennifer Elisseeff 232
Articular Cartilage Structure and Function 232
Bone Structure and Function 232
Natural Repair Capacity of Bone and Cartilage 233
Cartilage and Bone Development 233
Signaling in Development 235
Human Cartilage Repair Following Injury 236
Bone Tissue Repair Following Injury 236
Wound Healing and Limb Regeneration 237
Non-regenerative Tissues 239
Disease 239
Arthritis 240
Tissue Engineering of Cartilage and Bone 241
Cell Choice 241
Mesenchymal Stem Cells 242
Embryonic Stem Cells 243
Scaffolds 244
Bioactive Factors 245
Co-culture Models for Cartilage and Bone Reconstruction 246
Lingering Questions 247
References 247
Chapter 13 Blood Vessels Masayuki Yamato and Teruo Okano 256
Artery and Vein 256
The early tissue engineering of vascular grafts 256
Use of scaffolds for vascular grafts 256
Sheet-based tissue engineering 257
Capillary Networks 258
Drug delivery system (DDS) and controlled release 258
Endothelial cell transplantation 261
Microfluidics 261
Cell sheet engineering 261
Application to Hand Surgery 262
References 263
Chapter 14 Bench to Bedside: Navigating Industry, the FDA and Venture Capital Nicholas J. Panetta, Deepak M. Gupta, Michael T. Longaker and Geoffrey C. Gurtner 266
Introduction 266
Clinical Need Driven Innovation 267
Innovation in the Care of the Surgical Patient 268
Intellectual Property and the Patent Process 269
Proof of Concept 271
FDA and the Regulation of Surgical Inventions 272
Funding Acquisition 276
Commercialization 277
Summary 278
References 279
Index 282
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