Principles of Tissue Engineering -

Principles of Tissue Engineering (eBook)

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2000 | 2. Auflage
995 Seiten
Elsevier Science (Verlag)
978-0-08-053967-6 (ISBN)
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The opportunity that tissue engineering provides for medicine is extraordinary. In the United States alone, over half-a-trillion dollars are spent each year to care for patients who suffer from tissue loss or dysfunction. Although numerous books and reviews have been written on tissue engineering, none has been as comprehensive in its defining of the field. Principles of Tissue Engineering combines in one volume the prerequisites for a general understanding of tissue growth and development, the tools and theoretical information needed to design tissues and organs, as well as a presentation of applications of tissue engineering to diseases affecting specific organ systems. The first edition of the book, published in 1997, is the definite reference in the field. Since that time, however, the discipline has grown tremendously, and few experts would have been able to predict the explosion in our knowledge of gene expression, cell growth and differentiation, the variety of stem cells, new polymers and materials that are now available, or even the successful introduction of the first tissue-engineered products into the marketplace. There was a need for a new edition, and this need has been met with a product that defines and captures the sense of excitement, understanding and anticipation that has followed from the evolution of this fascinating and important field.

Key Features
* Provides vast, detailed analysis of research on all of the major systems of the human body, e.g., skin, muscle, cardiovascular, hematopoietic, and nerves
* Essential to anyone working in the field
* Educates and directs both the novice and advanced researcher
* Provides vast, detailed analysis of research with all of the major systems of the human body, e.g. skin, muscle, cardiovascular, hematopoietic, and nerves
* Has new chapters written by leaders in the latest areas of research, such as fetal tissue engineering and the universal cell
* Considered the definitive reference in the field
* List of contributors reads like a who's who of tissue engineering, and includes Robert Langer, Joseph Vacanti, Charles Vacanti, Robert Nerem, A. Hari Reddi, Gail Naughton, George Whitesides, Doug Lauffenburger, and Eugene Bell, among others
The opportunity that tissue engineering provides for medicine is extraordinary. In the United States alone, over half-a-trillion dollars are spent each year to care for patients who suffer from tissue loss or dysfunction. Although numerous books and reviews have been written on tissue engineering, none has been as comprehensive in its defining of the field. Principles of Tissue Engineering combines in one volume the prerequisites for a general understanding of tissue growth and development, the tools and theoretical information needed to design tissues and organs, as well as a presentation of applications of tissue engineering to diseases affecting specific organ systems. The first edition of the book, published in 1997, is the definite reference in the field. Since that time, however, the discipline has grown tremendously, and few experts would have been able to predict the explosion in our knowledge of gene expression, cell growth and differentiation, the variety of stem cells, new polymers and materials that are now available, or even the successful introduction of the first tissue-engineered products into the marketplace. There was a need for a new edition, and this need has been met with a product that defines and captures the sense of excitement, understanding and anticipation that has followed from the evolution of this fascinating and important field.Key Features* Provides vast, detailed analysis of research on all of the major systems of the human body, e.g., skin, muscle, cardiovascular, hematopoietic, and nerves* Essential to anyone working in the field* Educates and directs both the novice and advanced researcher* Provides vast, detailed analysis of research with all of the major systems of the human body, e.g. skin, muscle, cardiovascular, hematopoietic, and nerves* Has new chapters written by leaders in the latest areas of research, such as fetal tissue engineering and the universal cell* Considered the definitive reference in the field* List of contributors reads like a "e;who's who"e; of tissue engineering, and includes Robert Langer, Joseph Vacanti, Charles Vacanti, Robert Nerem, A. Hari Reddi, Gail Naughton, George Whitesides, Doug Lauffenburger, and Eugene Bell, among others

Front Cover 1
Principles of Tissue Engineering 4
Contents 8
Contributors 23
Foreword 30
Preface to the Second Edition 32
Preface to the First Edition 34
Tissue Engineering in Perspective 36
Origins of Tissue Engineering 36
The Tissue Engineering Triad 36
What Parts of the Body Can Tissue Engineering Replace? 37
Acellular Prostheses 38
The Relevance of Developmental Biology 38
Can Nature Be Imitated? 39
The Need for Vascularization in Vitro and in Vivo 40
Stem Cells 40
Cell Signaling 40
Looking Forward 41
References 41
Introduction to Tissue Engineering 44
Chapter 1. The History and Scope of Tissue Engineering 46
Introduction 46
Scientific Challenges 47
General Scientific Issues 49
Social Challenges 49
References 50
Chapter 2. The Challenge of Imitating Nature 52
Introduction 52
Cell Technology 53
Construct Technology 55
Integration into the Living System 56
Concluding Discussion 57
References 58
Part I: The Basis of Growth and Differentiation 60
Chapter 3. Organization of Cells into Higher Ordered Structures 62
Introduction 62
Cellular Changes Involved in the EMT 63
Stimuli of the Transformation 67
Conclusion 69
References 70
Chapter 4. Dynamics of Cell–ECM Interactions 76
Introduction 76
Composition and Diversity of the ECM 77
Receptors for Extracellular Matrix Molecules 77
Cell–ECM Interactions 79
Signal Transduction Events during Cell–ECM Interactions 85
Relevance for Tissue Engineering 89
References 91
Chapter 5. Matrix Molecules and Their Ligands 100
Introduction 100
Fibrillar Collagens: Major Scaffold Proteins in the ECM 101
Elastic Fibers and Microfibrils 106
Fibronectin: A Multidomain, Multifunctional Adhesive ECM Glycoprotein 106
Laminins: Large, Adhesive Basement Membrane Molecules 107
Modulators of Cell–Matrix Interactions 109
Proteoglycans: Multifunctional ECM and Cell Surface Molecules 110
Summary 111
References 111
Chapter 6. Inductive Phenomena 116
Introduction 116
Epithelial to Mesenchymal Signaling in Endoderm Development 116
Lung Development and Instructive Signaling 116
Permissive Signaling during Pancreas Development 118
References 121
Chapter 7. Morphogenesis and Tissue Engineering 124
Introduction 124
Bone Morphogenetic Proteins 125
Cartilage-Derived Morphogenetic Proteins 127
Pleitropy and Thresholds 128
BMPs Bind to Extracellular Matrix 128
BMPs: Actions Beyond Bone 128
BMP Receptors 128
Responding Stem Cells 129
Morphogens and Gene Therapy 130
Biomimetic Biomaterials 130
Tissue Engineering of Bones and Joints 131
Future Challenges 131
References 132
Chapter 8. Cell Determination and Differentiation 136
Introduction 136
Roles of MRFs during Embryogenesis 137
Initiation of Skeletal Muscle Development 138
References 139
Part II: In Vitro Control of Tissue Development 142
Chapter 9. Mechanical and Chemical Determinants of Tissue Development 144
Introduction 144
Extracellular Matrix Structure and Function 144
Pattern Formation through ECM Remodeling 147
Mechanochemical Switching between Growth and Differentiation 148
Summary 150
References 151
Chapter 10. Animal Cell Culture 154
References 159
Chapter 11. Regulation of Cell Behavior by Matricellular Proteins 162
Introduction 162
Matricellular Proteins 162
Conclusions 167
References 168
Chapter 12. Growth Factors 172
Introduction 172
Wound Healing 173
Role of Basic Fibroblast Growth Factor and Angiogenesis 179
Other Roles of Growth Factors and Cytokines 180
Conclusions 180
References 180
Chapter 13. Tissue Engineering Bioreactors 186
Introduction 186
Cell–Polymer Constructs 186
Bioreactor Technologies 187
Bioreactor Modulation of Tissue Formation 190
Bioreactor Cultivation of Functional Tissues 194
Tissue Engineering Bioreactors: State of the Art 195
Summary and Research Needs 197
References 197
Chapter 14. Tissue Assembly in Microgravity 200
Introduction 200
Microgravity as a Novel Tissue Culture Venue 201
Vascularization: Overcoming Size Limitations of Tissue Assemblies 202
From Single Cells to Tissues in Space 202
In Vitro Embryology 203
Gravitational Sensing 204
Caveats 204
Conclusions 205
References 205
Part III: In Vivo Synthesis of Tissues and Organs 208
Chapter 15. In Vivo Synthesis of Tissues and Organs 210
Scale of Functional Deficit: Macromolecule versus Organ 210
Basic Parameters of the Living Environment during in Vivo Organ Synthesis 211
Fundamental Design Principles for Tissue and Organ Regeneration Templates 213
Examples of in Vivo Organ Synthesis 217
Summary 220
References 220
Part IV. Models for Tissue Engineering 222
Chapter 16. Organotypic and Histiotypic Models of Engineered Tissues 224
Introduction 224
The Collagen Gel Model 224
Models of Cell Interactions in Collagen Lattices 225
Other Types of Epithelial–Mesenchymal Models 227
Vascular Models 229
Selection of Scaffolds Other Than Gels for Model Systems 231
Cell Signaling and the Enrichment of Scaffolds 232
Goals and Uses of Model Tissue and Organ Building 233
References 234
Chapter 17. Quantitative Aspects of Tissue Engineering: Basic Issues in Kinetics, Transport, and Mechanics 238
Introduction 238
Molecular Interactions with Cells 241
Molecular and Cell Transport through Tissue 241
Cell and Tissue Mechanics 244
References 248
Part V: Biomaterials in Tissue Engineering 250
Chapter 18. Patterning of Cells and Their Environment 252
Introduction 252
Soft Lithography 252
Self-Assembled Monolayers 253
Microcontact Printing 255
Microfluidic Patterning 257
Laminar Flow Patterning 259
Conclusion and Future Prospects 260
References 261
Chapter 19. Cell Interactions with Polymers 264
Introduction 264
Methods for Characterizing Cell Interactions with Polymers 264
Cell Interaction with Polymer Surfaces 267
Cell Interactions with Polymers in Suspension 272
Cell Interactions with Three-Dimensional Polymer Scaffolds and Gels 273
References 274
Chapter 20. Matrix Effects 280
Introduction 280
Extracellular Matrix Proteins and Their Receptors 280
Model Systems for Study of Matrix Interactions 285
Cell Pattern Formation by Substrate Patterning 287
Signal Transduction and Functional Regulation via the Extracellular Matrix 287
Translation to Working Biomaterial Systems 289
References 289
Chapter 21. Polymer Scaffold Processing 294
Introduction 294
Fiber Bonding 295
Solvent Casting and Particulate Leaching 296
Membrane Lamination 298
Melt Molding 299
Extrusion 299
Three-Dimensional Printing 300
Gas Foaming 300
Freeze Drying 301
Phase Separation 301
Polymer/Ceramic Composite Foams 302
In Situ Polymerization 303
Conclusions 304
References 304
Chapter 22. Biodegradable Polymers 306
Introduction 306
Biodegradable Polymer Selection Criteria 306
Biologically Derived Bioresorbables 307
Experimental Biologically Derived Bioresorbables 309
Creating Materials for Tissue-Engineered Products 316
Conclusion 317
References 317
Part VI: Transplantation of Engineered Cells and Tissues 322
Chapter 23. Approaches to Transplanting Engineered Cells and Tissues 324
Introduction 324
Developing Workable Strategies 324
Mode of Action—An Important Design Consideration 326
Role of the Host 327
Source of Cells 328
The Immunology of Nonautologous Cells 330
Safety Considerations 331
Conclusion 331
References 332
Chapter 24. Cryopreservation 336
Introduction 336
Applications of Cryopreservation Technology in Tissue Engineering 336
Challenges in Cryopreservation Protocol Development 337
Cryobiology of Cells 338
Cryobiology of Tissue 345
Summary and Future Directions 347
References 348
Chapter 25. Immunomodulation 352
Introduction 352
Origin of the Designer Tissue Concept 353
Expansion of Research on Designer Tissues 354
Mechanisms of Graft Survival after Class I Donor Ablation or Antibody Masking 357
The Launching of Xenogeneic Human Clinical Trials in the United States Using Immunomodulation 359
Gene Addition 360
RNA Ablation 360
Comment 361
References 361
Chapter 26. Immunoisolation 364
Introduction 364
Technology 364
Clinical 366
Future Directions 369
References 371
Chapter 27. Engineering Challenges in Immunoisolation Device Development 374
Introduction 374
Engineering Challenges 374
Oxygen-Supply Limitations 379
Theoretical Analysis of in Situ Oxygen Generation 382
Calculations 388
Concluding Remarks 391
References 391
Part VII: Fetal Tissue Engineering 394
Chapter 28. Fetal Tissue Engineering 396
Introduction 396
General Characteristics of Fetal Cells 397
The Fetus as a Transplantation Host 398
Fetal Tissue Engineering 400
Ethical Considerations 403
Future Perspectives 406
References 407
Chapter 29. Pluripotent Stem Cells 412
Introduction 412
Differentiation in Vitro 414
Examples of in Vitro Differentiation and Markers 417
In Vivo Applications 419
Summary and Future Prospects 421
References 421
Part VIII: Gene Therapy 426
Chapter 30. Gene-Based Therapeutics 428
Introduction 428
Gene Delivery 429
Persistent Gene Expression 433
Safety Considerations for Gene-Based Therapeutics 437
Large-Scale Production Issues 439
Conclusion 440
References 440
Part IX. Breast 450
Chapter 31. Breast Reconstruction 452
Introduction 452
Cell Types for Soft Tissue Engineering 453
Materials 455
Animal Models 460
Strategies to Enhance the Vascularization of Engineered Tissue 462
Concluding Remarks 463
References 463
Part X: Cardiovascular System 468
Chapter 32. Blood Vessels 470
Introduction 470
Graft Healing 471
Strategies for the Development of Vascular Grafts 475
References 484
Chapter 33. Small-Diameter Vascular Grafts 490
Introduction 490
Synthetic Grafts 491
In Vitro Blood Vessel Tissue Engineering 491
In Vivo Tissue Engineering of Blood Vessels 492
Summary 496
References 496
Chapter 34. Cardiac Prostheses 498
Introduction 498
A Short History of Tissue Heart Valves 499
The Status of Tissue Valves in 1999 502
The Issue of Whether to Use a Stent 504
The Issue of Repair versus Replacement 506
Speculation about the Future 506
Recent Developments 507
The Ideal Valve Repair or Replacement 508
References 509
Part XI: Cornea 512
Chapter 35. Cornea 514
Introduction 514
Biology of the Cornea 516
Criteria for Keratoprostheses 520
Development of the Keratoprosthesis 521
Evaluation of Intact Devices 527
Other Devices Used to Change the Curvature of the Cornea 532
References 532
Part XII: Endocrinology and Metabolism 536
Chapter 36. Bioartificial Pancreas 538
Introduction 538
Theoretical Background 540
Experiment 543
Capsule Development 544
Discussion 547
References 548
Chapter 37. Parathyroid 552
History of Parathyroid Allotransplantation 552
Hypoparathyroidism 554
Microencapsulation 559
Alginates 559
Experimental and Clinical Transplantation of Microencapsulated Parathyroid Tissue 560
Alternative Approaches and Perspectives 560
References 561
Part XIII: Gastrointestinal System 566
Chapter 38. Alimentary Tract 568
Introduction 568
Enterocyte Isolation 571
Procedural Steps 573
Discussion 575
References 580
Chapter 39. Liver 584
Introduction 584
Anatomy and Function of the Liver 584
Liver Failure: Pathophysiological Classification 587
Mechanisms of HE in Liver Failure 588
Medical Need for Liver-Assist Devices 588
Biological Component of Liver-Assist Devices 589
Liver-Assist Device Configurations 591
References 593
Chapter 40. HepatAssist Liver Support System 596
Introduction 596
HepatAssist System 596
Cell Preparation 596
Clinical Study 597
Conclusion 600
References 600
Chapter 41. Lineage Biology and Liver 602
Introduction 602
Liver Organization and Development 603
Identification, Isolation, and Sourcing of Cells for Tissue Engineering 605
Sourcing of Human Cells for Tissue Engineering 612
Microenvironment 613
Biodegradable Polymers 619
Designing Bioreactors for Tissue Engineering 626
Technical Aspects of Tissue Engineering 628
Future Considerations 630
Summary 631
References 632
Part XIV: Hematopoietic System 642
Chapter 42. Red Blood Cell Substitutes 644
Introduction 644
Why Do We Have to Modify Hemoglobin? 644
Sources of Hemoglobin 648
Circulating Time of Modified Hemoglobin 649
Safety of Modified Hemoglobin Blood Substitute 649
Efficacy of Modified Hemoglobin Blood Substitute 650
Present Status and Future Research and Development 650
References 651
Chapter 43. Lymphoid Cells 654
Introduction 654
Lymphocyte Engineering: Reality and Potential 655
Concluding Remarks and Prospects for Lymphocyte Engineering 668
References 669
Chapter 44. Hematopoietic Stem Cells 674
Introduction 674
Overview of Hematopoiesis: Properties and Regulation of Hematopoietic Stem Cells Relevant to Tissue Engineering 675
Organization of the Stem Cell Compartment 676
Stromal Microenvironments 676
References 681
Part XV: Kidney and Genitourinary System 686
Chapter 45. Renal Replacement Devices 688
Introduction 688
Basics of Kidney Function 688
Tissue Engineering Approach to Renal Function Replacement 689
Summary 695
References 695
Chapter 46. Genitourinary System 698
Introduction 698
Tissue Engineering Strategies in the Genitourinary System 698
Engineering Genitourinary Tissues 699
Future Directions 707
References 707
Part XVI. Musculoskeletal System 712
Chapter 47. Structural Tissue Engineering 714
Introduction 714
Materials Development 715
Structural Tissues 717
Biomechanics 722
Conclusion 723
References 723
Chapter 48. Bone Regeneration through Cellular Engineering 726
Introduction 726
Marrow: The Source of Mesenchymal Progenitor Cells 726
Delivery of Osteoprogenitor Cells 730
Bone Regeneration by MSCs 732
MSCs and Gene Therapy 735
Prevention of Age-Related Bone Loss 736
Conclusion 737
References 737
Chapter 49. Articular Cartilage Injury 740
Introduction 740
Autologous Chondrocyte Transplantation 742
Commercialization of Autologous Chondrocyte Implantation 744
Alternative Strategies for the Delivery of Cell-Based Therapies for Cartilage Repair 749
Conclusions 750
References 751
Chapter 50. Tendons and Ligamensts 754
Introduction 754
The Need for Bioengineered Tendon and Ligament Substitutes 754
Histologic Description of Tendons and Ligaments 755
Production of Bioengineered Tendons and Ligaments 756
A New Living Bioengineered Ligament Model 756
Technical Steps to Produce and Analyze Our bACL 758
Conclusions 761
Perspectives in Tendon and Ligament Bioengineering 762
References 763
Chapter 51. Mechanosensory Mechanisms in Bone 766
Introduction 766
The Connected Cellular Network 767
Mechanosensation on the CCN 768
Questions for Future Research Socratic Questions
References 775
Chapter 52. Myoblast Therapy 782
Introduction 782
Myoblast-Mediated Gene Transfer 782
Therapeutic Myoblast Transplantation for Myopathies 783
References 788
Part XVII: Nervous System 792
Chapter 53. Protection and Repair of Hearing 794
Introduction 794
Basis for Interventions 794
Methods of Intervention 798
Conclusions 800
References 800
Chapter 54. Vision Enhancement Systems 804
Visual System: Architecture and (Dys)Function 804
Possible Approaches to Vision Restoration 806
Current Approaches 806
Applications of Engineered Cells and Tissues: Challenges and Tentative Solutions 811
Toward “2020” Vision 813
References 813
Chapter 55. Brain Implants 816
Introduction 816
Naked Cell Implants 816
Encapsulated Cell Implants 820
Controlled-Release Implants 820
Axonal Guidance Implants 821
Disease Targets 821
Surgical Considerations 823
Conclusions 823
References 823
Chapter 56. Nerve Regeneration 828
Nerve Regeneration and Neural Tissue Engineering 828
Overview of Neural Regeneration 829
Experimental Use of Guidance Channels 831
Biomaterial-Based Approaches to Nerve Repair 833
Tissue Engineering Approaches to Nerve Repair 837
Specificity of Nerve Reconnections 839
Summary 839
References 839
Chapter 57. Transplantation Strategies for Treatment of Spinal Cord Dysfunction and Injury 842
Introduction 842
Spinal Implants as Axon Bridges 842
Spinal Implants for Replacement of Specific Cell Populations 848
Spinal Implants for Provision of Neurotransmitters 851
References 856
Chapter 58. Neural Stem Cells 864
Introduction 864
Background 864
Neural Stem Cell Applications in Tissue Engineering 867
Summary 871
References 871
Part XVIII: Periodontal and Dental Applications 874
Chapter 59. Periodontal Applications 876
Introduction 876
Guided Tissue Regeneration 877
Bone Substitutes 879
Dental Implants 881
Growth Factors and Plasma Proteins 882
Cell Culture Techniques 886
Conclusion 886
References 886
Chapter 60. Regeneration of Dentin 890
Introduction 890
Dentin 890
Bone Morphogenetic Proteins 890
Induction Potential of Dentin 891
Recombinant Human BMPs Induce Dentin Formation 891
Delivery Systems 893
Clinical Considerations 893
Additional Considerations 894
Potential Applications of BMP-Induced Dentinogenesis 894
References 895
Part XIX: Skin 898
Chapter 61. Wound Repair: Basic Biology to Tissue Engineering 900
Introduction 900
Inflammation 901
Epithelialization 901
Granulation Tissue 905
Wound Contraction and Extracellular Matrix Reorganization 911
References 913
Chapter 62. Skin 922
Introduction 922
Skin Structure and Function 923
Engineering Skin Tissue 926
Epidermal Regeneration 927
Dermal Replacement 927
Composite Skin Grafts 928
Conclusion 930
References 930
Chapter 63. Dermal Equivalents 934
Introduction 934
Cell Testing and Establishment of Manufacturing Cell Banks 934
Manufacturing a Dermal Replacement 934
Clinical Results of Wound Healing 943
Summary 944
References 944
Part XX: Womb 946
Chapter 64. Artificial Womb 948
What Does the Field of Tissue Engineering Have to Offer the Premature Infant? 949
Prematurity—The Consequences 949
The Ideal Artificial Womb 950
State-of-the-Art Artificial Placenta Design 952
Organ Maturation during Maintenance with Artificial Womb 954
Variations of Artificial Womb Technology 954
Conclusion 955
References 955
Part XXI: Regulatory Issues 956
Chapter 65. Regulatory Considerations 958
Introduction 958
Legislative Authority/Oversight 959
Product Evaluation and the Regulatory Process 960
Recent Developments in Product Evaluation 965
Interaction between FDA Headquarters and Field Offices 968
Development of Standards 968
Communications with Industry 969
The FDA and Future Perspectives for Tissue-Engineered Medical Products 970
References 970
Epilogue 972
Index 974

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