| Contributors |
| Foreword |
| Preface to the Second Edition |
| Preface to the First Edition |
| Tissue Engineering in Perspective / Eugene Bell |
| Origins of Tissue Engineering |
| The Tissue Engineering Triad |
| What Parts of the Body Can Tissue Engineering Replace? |
| Acellular Prostheses |
| The Relevance of Developmental Biology |
| Can Nature Be Imitated? |
| The Need for Vascularization in Vitro and in Vivo |
| Stem Cells |
| Cell Signaling |
| Looking Forward |
| References |
| Introduction to Tissue Engineering |
| The History and Scope of Tissue Engineering / Joseph P. Vacanti ; Charles A. Vacanti1.： |
| Introduction |
| Scientific Challenges |
| General Scientific Issues |
| Social Challenges |
| The Challenge of Imitating Nature / Robert M. Nerem2.： |
| Cell Technology |
| Construct Technology |
| Integration into the Living System |
| Concluding Discussion |
| The Basis of Growth and Differentiation / Part I.： |
| Organization of Cells into Higher Ordered Structures / Carol A. Erickson3.： |
| Cellular Changes Involved in the EMT |
| Stimuli of the Transformation |
| Conclusion |
| Dynamics of Cell-ECM Interactions / Manuela Martins-Green4.： |
| Composition and Diversity of the ECM |
| Receptors for Extracellular Matrix Molecules |
| Cell-ECM Interactions |
| Signal Transduction Events during Cell-ECM Interactions |
| Relevance for Tissue Engineering |
| Matrix Molecules and Their Ligands / Bjorn Reino Olsen5.： |
| Fibrillar Collagens: Major Scaffold Proteins in the ECM |
| Elastic Fibers and Microfibrils |
| Fibronectin: A Multidomain, Multifunctional Adhesive ECM Glycoprotein |
| Laminins: Large, Adhesive Basement Membrane Molecules |
| Modulators of Cell-Matrix Interactions |
| Proteoglycans: Multifunctional ECM and Cell Surface Molecules |
| Summary |
| Inductive Phenomena / Matthias Hebrok ; Douglas A. Melton6.： |
| Epithelial to Mesenchymal Signaling in Endoderm Development |
| Lung Development and Instructive Signaling |
| Permissive Signaling during Pancreas Development |
| Morphogenesis and Tissue Engineering / A. H. Reddi7.： |
| Bone Morphogenetic Proteins |
| Cartilage-Derived Morphogenetic Proteins |
| Pleitropy and Thresholds |
| BMPs Bind to Extracellular Matrix |
| BMPs: Actions Beyond Bone |
| BMP Receptors |
| Responding Stem Cells |
| Morphogens and Gene Therapy |
| Biomimetic Biomaterials |
| Tissue Engineering of Bones and Joints |
| Future Challenges |
| Cell Determination and Differentiation / Leon W. Browder8.： |
| Roles of MRFs during Embryogenesis |
| Initiation of Skeletal Muscle Development |
| In Vitro Control of Tissue Development / Part II.： |
| Mechanical and Chemical Determinants of Tissue Development / Donald E. Ingber9.： |
| Extracellular Matrix Structure and Function |
| Pattern Formation through ECM Remodeling |
| Mechanochemical Switching between Growth and Differentiation |
| Animal Cell Culture / Gordon H. Sato ; David W. Barnes10.： |
| Regulation of Cell Behavior by Matricellular Proteins / Amy D. Bradshaw ; E. Helene Sage11.： |
| Matricellular Proteins |
| Conclusions |
| Growth Factors / Thomas F. Deuel ; Nan Zhang12.： |
| Wound Healing |
| Role of Basic Fibroblast Growth Factor and Angiogenesis |
| Other Roles of Growth Factors and Cytokines |
| Tissue Engineering Bioreactors / Lisa E. Freed ; Gordana Vunjak-Novakovic13.： |
| Cell-Polymer Constructs |
| Bioreactor Technologies |
| Bioreactor Modulation of Tissue Formation |
| Bioreactor Cultivation of Functional Tissues |
| Tissue Engineering Bioreactors: State of the Art |
| Summary and Research Needs |
| Tissue Assembly in Microgravity / Brian R. Unsworth ; Peter I. Lelkes14.： |
| Microgravity as a Novel Tissue Culture Venue |
| Vascularization: Overcoming Size Limitations of Tissue Assemblies |
| From Single Cells to Tissues in Space |
| In Vitro Embryology |
| Gravitational Sensing |
| Caveats |
| In Vivo Synthesis of Tissues and Organs / Part III.： |
| Scale of Functional Deficit: Macromolecule versus Organ / Ioannis V. Yannas15.： |
| Basic Parameters of the Living Environment during in Vivo Organ Synthesis |
| Fundamental Design Principles for Tissue and Organ Regeneration Templates |
| Examples of in Vivo Organ Synthesis |
| Models for Tissue Engineering / Part IV.： |
| Organotypic and Histiotypic Models of Engineered Tissues / 16.： |
| The Collagen Gel Model |
| Models of Cell Interactions in Collagen Lattices |
| Other Types of Epithelial-Mesenchymal Models |
| Vascular Models |
| Selection of Scaffolds Other Than Gels for Model Systems |
| Cell Signaling and the Enrichment of Scaffolds |
| Goals and Uses of Model Tissue and Organ Building |
| Quantitative Aspects of Tissue Engineering: Basic Issues in Kinetics, Transport, and Mechanics / Alan J. Grodzinsky ; Roger D. Kamm ; Douglas A. Lauffenburger17.： |
| Molecular Interactions with Cells |
| Molecular and Cell Transport through Tissue |
| Cell and Tissue Mechanics |
| Biomaterials in Tissue Engineering / Part V.： |
| Patterning of Cells and Their Environment / Shuichi Takayama ; Robert G. Chapman ; Ravi S. Kane ; George M. Whitesides18.： |
| Soft Lithography |
| Self-Assembled Monolayers |
| Microcontact Printing |
| Microfluidic Patterning |
| Laminar Flow Patterning |
| Conclusion and Future Prospects |
| Cell Interactions with Polymers / W. Mark Saltzman19.： |
| Methods for Characterizing Cell Interactions with Polymers |
| Cell Interaction with Polymer Surfaces |
| Cell Interactions with Polymers in Suspension |
| Cell Interactions with Three-Dimensional Polymer Scaffolds and Gels |
| Matrix Effects / Jeffrey A. Hubbell20.： |
| Extracellular Matrix Proteins and Their Receptors |
| Model Systems for Study of Matrix Interactions |
| Cell Pattern Formation by Substrate Patterning |
| Signal Transduction and Functional Regulation via the Extracellular Matrix |
| Translation to Working Biomaterial Systems |
| Polymer Scaffold Processing / Robert C. Thomson ; Albert K. Shung ; Michael J. Yaszemski ; Antonios G. Mikos21.： |
| Fiber Bonding |
| Solvent Casting and Particulate Leaching |
| Membrane Lamination |
| Melt Molding |
| Extrusion |
| Three-Dimensional Printing |
| Gas Foaming |
| Freeze Drying |
| Phase Separation |
| Polymer/Ceramic Composite Foams |
| In Situ Polymerization |
| Biodegradable Polymers / James M. Pachence ; Joachim Kohn22.： |
| Biodegradable Polymer Selection Criteria |
| Biologically Derived Bioresorbables |
| Experimental Biologically Derived Bioresorbables |
| Creating Materials for Tissue-Engineered Products |
| Transplantation of Engineered Cells and Tissues / Part VI.： |
| Approaches to Transplanting Engineered Cells and Tissues / Janet Hardin-Young ; Jeffrey Teumer ; Robert N. Ross ; Nancy L. Parenteau23.： |
| Developing Workable Strategies |
| Mode of Action--An Important Design Consideration |
| Role of the Host |
| Source of Cells |
| The Immunology of Nonautologous Cells |
| Safety Considerations |
| Cryopreservation / Jens O. M. Karlsson ; Mehmet Toner24.： |
| Applications of Cryopreservation Technology in Tissue Engineering |
| Challenges in Cryopreservation Protocol Development |
| Cryobiology of Cells |
| Cryobiology of Tissue |
| Summary and Future Directions |
| Immunomodulation / Denise Faustman25.： |
| Origin of the Designer Tissue Concept |
| Expansion of Research on Designer Tissues |
| Mechanisms of Graft Survival after Class I Donor Ablation or Antibody Masking |
| The Launching of Xenogeneic Human Clinical Trials in the United States Using Immunomodulation |
| Gene Addition |
| RNA Ablation |
| Comment |
| Immunoisolation / Beth A. Zielinski ; Michael J. Lysaght26.： |
| Technology |
| Clinical |
| Future Directions |
| Engineering Challenges in Immunoisolation Device Development / Efstathios S. Avgoustiniatos ; Haiyan Wu ; Clark K. Colton27.： |
| Engineering Challenges |
| Oxygen-Supply Limitations |
| Theoretical Analysis of in Situ Oxygen Generation |
| Calculations |
| Concluding Remarks |
| Fetal Tissue Engineering / Part VII.： |
| General Characteristics of Fetal Cells / Dario O. Fauza28.： |
| The Fetus as a Transplantation Host |
| Ethical Considerations |
| Future Perspectives |
| Pluripotent Stem Cells / Michael J. Shamblott ; Brian E. Edwards ; John D. Gearhart29.： |
| Differentiation in Vitro |
| Examples of in Vitro Differentiation and Markers |
| In Vivo Applications |
| Summary and Future Prospects |
| Gene Therapy / Part VIII.： |
| Gene-Based Therapeutics / Lee G. Fradkin ; J. Dezz Ropp ; John F. Warner30.： |
| Gene Delivery |
| Persistent Gene Expression |
| Safety Considerations for Gene-Based Therapeutics |
| Large-Scale Production Issues |
| Breast / Part IX.： |
| Breast Reconstruction / Kuen Young Lee ; Craig R. Halberstadt ; Walter D. Holder ; David J. Mooney31.： |
| Cell Types for Soft Tissue Engineering |
| Materials |
| Animal Models |
| Strategies to Enhance the Vascularization of Engineered Tissue |
| Cardiovascular System / Part X.： |
| Blood Vessels / Lian Xue ; Howard P. Greisler32.： |
| Graft Healing |
| Strategies for the Development of Vascular Grafts |
| Small-Diameter Vascular Grafts / Susan J. Sullivan ; Kelvin G. M. Brockbank33.： |
| Synthetic Grafts |
| In Vitro Blood Vessel Tissue Engineering |
| In Vivo Tissue Engineering of Blood Vessels |
| Cardiac Prostheses / Jack W. Love34.： |
| A Short History of Tissue Heart Valves |
| The Status of Tissue Valves in 1999 |
| The Issue of Whether to Use a Stent |
| The Issue of Repair versus Replacement |
| Speculation about the Future |
| Recent Developments |
| The Ideal Valve Repair or Replacement |
| Cornea / Part XI.： |
| Biology of the Cornea / Vickery Trinkaus-Randall35.： |
| Criteria for Keratoprostheses |
| Development of the Keratoprosthesis |
| Evaluation of Intact Devices |
| Other Devices Used to Change the Curvature of the Cornea |
| Endocrinology and Metabolism / Part XII.： |
| Bioartificial Pancreas / Taylor G. Wang ; Robert P. Lanza36.： |
| Theoretical Background |
| Experiment |
| Capsule Development |
| Discussion |
| Parathyroid / C. Hasse ; A. Zielke ; T. Bohrer ; U. Zimmermann ; M. Rothmund37.： |
| History of Parathyroid Allotransplantation |
| Hypoparathyroidism |
| Microencapsulation |
| Alginates |
| Experimental and Clinical Transplantation of Microencapsulated Parathyroid Tissue |
| Alternative Approaches and Perspectives |
| Gastrointestinal System / Part XIII.： |
| Alimentary Tract / Gregory M. Organ38.： |
| Enterocyte Isolation |
| Procedural Steps |
| Liver / Hugo O. Jauregui39.： |
| Anatomy and Function of the Liver |
| Liver Failure: Pathophysiological Classification |
| Mechanisms of HE in Liver Failure |
| Medical Need for Liver-Assist Devices |
| Biological Component of Liver-Assist Devices |
| Liver-Assist Device Configurations |
| HepatAssist Liver Support System / Claudy Mullon ; Barry A. Solomon40.： |
| HepatAssist System |
| Cell Preparation |
| Clinical Study |
| Lineage Biology and Liver / Arron S. L. Xu ; Thomas L. Luntz ; Jeffrey M. Macdonald ; Hiroshi Kubota ; Edward Hsu ; Robert E. London ; Lola M. Reid41.： |
| Liver Organization and Development |
| Identification, Isolation, and Sourcing of Cells for Tissue Engineering |
| Sourcing of Human Cells for Tissue Engineering |
| Microenvironment |
| Designing Bioreactors for Tissue Engineering |
| Technical Aspects of Tissue Engineering |
| Future Considerations |
| Hematopoietic System / Part XIV.： |
| Red Blood Cell Substitutes / Thomas Ming Swi Chang42.： |
| Why Do We Have to Modify Hemoglobin? |
| Sources of Hemoglobin |
| Circulating Time of Modified Hemoglobin |
| Safety of Modified Hemoglobin Blood Substitute |
| Efficacy of Modified Hemoglobin Blood Substitute |
| Present Status and Future Research and Development |
| Lymphoid Cells / Una Chen43.： |
| Lymphocyte Engineering: Reality and Potential |
| Concluding Remarks and Prospects for Lymphocyte Engineering |
| Hematopoietic Stem Cells / Anne Kessinger ; Graham Sharp44.： |
| Overview of Hematopoiesis: Properties and Regulation of Hematopoietic Stem Cells Relevant to Tissue Engineering |
| Organization of the Stem Cell Compartment |
| Stromal Microenvironments |
| Kidney and Genitourinary System / Part XV.： |
| Renal Replacement Devices / H. David Humes45.： |
| Basics of Kidney Function |
| Tissue Engineering Approach to Renal Function Replacement |
| Genitourinary System / Byung-Soo Kim ; Anthony Atala46.： |
| Tissue Engineering Strategies in the Genitourinary System |
| Engineering Genitourinary Tissues |
| Musculoskeletal System / Part XVI.： |
| Structural Tissue Engineering / Lawrence J. Bonassar47.： |
| Materials Development |
| Structural Tissues |
| Biomechanics |
| Bone Regeneration through Cellular Engineering / Scott P. Bruder ; Arnold I. Caplan48.： |
| Marrow: The Source of Mesenchymal Progenitor Cells |
| Delivery of Osteoprogenitor Cells |
| Bone Regeneration by MSCs |
| MSCs and Gene Therapy |
| Prevention of Age-Related Bone Loss |
| Articular Cartilage Injury / John M. McPherson ; Ross Tubo49.： |
| Autologous Chondrocyte Transplantation |
| Commercialization of Autologous Chondrocyte Implantation |
| Alternative Strategies for the Delivery of Cell-Based Therapies for Cartilage Repair |
| Tendons and Ligaments / Francine Goulet ; Denis Rancourt ; Rejean Cloutier ; Lucie Germain ; A. Robin Poole ; Francois A. Auger50.： |
| The Need for Bioengineered Tendon and Ligament Substitutes |
| Histologic Description of Tendons and Ligaments |
| Production of Bioengineered Tendons and Ligaments |
| A New Living Bioengineered Ligament Model |
| Technical Steps to Produce and Analyze Our bACL |
| Perspectives in Tendon and Ligament Bioengineering |
| Mechanosensory Mechanisms in Bone / Stephen C. Cowin ; Melvin L. Moss51.： |
| The Connected Cellular Network |
| Mechanosensation on the CCN |
| Questions for Future Research; Socratic Questions |
| Myoblast Therapy / Joanne C. Cousins ; Jennifer E. Morgan ; Terence A. Partridge52.： |
| Myoblast-Mediated Gene Transfer |
| Therapeutic Myoblast Transplantation for Myopathies |
| Nervous System / Part XVII.： |
| Protection and Repair of Hearing / Richard A. Altschuler ; Yehoash Raphael ; Jochen Schacht ; David J. Anderson ; Josef M. Miller53.： |
| Basis for Interventions |
| Methods of Intervention |
| Vision Enhancement Systems / Gislin Dagnelie ; Mark S. Humayun ; Robert W. Massof54.： |
| Visual System: Architecture and (Dys) Function |
| Possible Approaches to Vision Restoration |
| Current Approaches |
| Applications of Engineered Cells and Tissues: Challenges and Tentative Solutions |
| Toward "2020" Vision |
| Brain Implants / Lars U. Wahlberg55.： |
| Naked Cell Implants |
| Encapsulated Cell Implants |
| Controlled-Release Implants |
| Axonal Guidance Implants |
| Disease Targets |
| Surgical Considerations |
| Nerve Regeneration / Eric G. Fine ; Robert F. Valentini ; Patrick Aebischer56.： |
| Nerve Regeneration and Neural Tissue Engineering |
| Overview of Neural Regeneration |
| Experimental Use of Guidance Channels |
| Biomaterial-Based Approaches to Nerve Repair |
| Tissue Engineering Approaches to Nerve Repair |
| Specificity of Nerve Reconnections |
| Transplantation Strategies for Treatment of Spinal Cord Dysfunction and Injury / Jacqueline Sagen ; Mary Bartlett Bunge ; Naomi Kleitman57.： |
| Spinal Implants as Axon Bridges |
| Spinal Implants for Replacement of Specific Cell Populations |
| Spinal Implants for Provision of Neurotransmitters |
| Neural Stem Cells / Martin P. Vacanti58.： |
| Background |
| Neural Stem Cell Applications in Tissue Engineering |
| Periodontal and Dental Applications / Part XVIII.： |
| Periodontal Applications / Neal A. Miller ; Marie C. Bene ; Jacques Penaud ; Pascal Ambrosini ; Gilbert C. Faure59.： |
| Guided Tissue Regeneration |
| Bone Substitutes |
| Dental Implants |
| Growth Factors and Plasma Proteins |
| Cell Culture Techniques |
| Regeneration of Dentin / R. Bruce Rutherford60.： |
| Dentin |
| Induction Potential of Dentin |
| Recombinant Human BMPs Induce Dentin Formation |
| Delivery Systems |
| Clinical Considerations |
| Additional Considerations |
| Potential Applications of BMP-Induced Dentinogenesis |
| Skin / Part XIX.： |
| Wound Repair: Basic Biology to Tissue Engineering / Richard A. F. Clark ; Adam J. Singer61.： |
| Inflammation |
| Epithelialization |
| Granulation Tissue |
| Wound Contraction and Extracellular Matrix Reorganization |
| Skin Structure and Function / 62.： |
| Engineering Skin Tissue |
| Epidermal Regeneration |
| Dermal Replacement |
| Composite Skin Grafts |
| Dermal Equivalents / Gail K. Naughton63.： |
| Cell Testing and Establishment of Manufacturing Cell Banks |
| Manufacturing a Dermal Replacement |
| Clinical Results of Wound Healing |
