Translational Approaches in Tissue Engineering and Regenerative Medicine -- Contents -- Preface -- PART I Principles of Regenerative Medicine -- Chapter 1 Tissue Engineering and RegenerativeMedicine: Advancing Toward ClinicalTherapies -- 1.1 Introduction -- 1.2 Historical Perspective -- 1.3 Cell Sourcing -- 1.4 Enabling Technologies -- 1.5 Vascularization and Innervation -- 1.6 Beyond the Science -- 1.7 Nonscience Hurdles -- 1.8 Conclusions -- Acknowledgments -- References -- Chapter 2 Clinical Perspective of Tissue Engineeringand Cell-Based Therapies -- 2.1 Introduction -- 2.2 Musculoskeletal System -- 2.3 Urinary System -- 2.4 Gastrointestinal System -- 2.5 Cardiovascular System -- 2.6 Pulmonary System -- 2.7 Neurologic System -- 2.8 Conclusion -- References -- PART II Stem Cells in Regenerative Medicine -- Chapter 3 Embryonic Stem Cells and DifferentiationPathways -- 3.1 Introduction -- 3.2 Propagating ESCs in an Undifferentiated State and Additional Amplification by Isolating Purified Tissue-Specific Stem Cells -- 3.3 Embryonic Stem Cell Differentiation via Embryoid Bodies -- 3.4 Mouse Models and Large-Scale Genomic Analysis Allows Us to Identify Factors, with One Caveat -- 3.5 Differentiation into Specific Cell Types -- 3.5.1 Pancreatic Islet Cells -- 3.5.1.1 In Vitro Differentiation to Insulin-Secreting Cells -- 3.5.2 Liver -- 3.5.2.1 Progress from ESCs to Hepatocytes -- 3.5.3 Neural Applications -- 3.6 Screening Needs -- 3.7 Summary -- References -- Chapter 4 Hematopoietic Stem Cells and Regenerative Medicine -- 4.1 Definition of Hematopoietic Stem Cell and Stem Cell Hierarchy -- 4.1.1 Stem Cell Markers-Immunophenotype -- 4.1.2 Methods for Isolating Hematopoietic Stem Cells -- 4.2 Stem Cell Characteristics -- 4.3 Transplantation -- 4.4 Source of Stem Cells -- 4.4.1 Storage of HSCs -- 4.5 HSC Therapy in Cardiac Disease -- References.

PART III Regeneration of Tissues and Organs:Translational Approaches -- Chapter 5 Translational and Clinical Requirementsfor Bioengineered Skin -- 5.1 Introduction -- 5.2 Regulation of Tissue-Engineered Products -- 5.3 Design of a Tissue-Engineered Product -- 5.3.1 Cell Source: Autologous or Allogeneic -- 5.3.2 Manufacturing Process -- 5.3.3 Bioreactors -- 5.4 Final Product Testing -- 5.5 Clinical Trials -- 5.6 Summary -- References -- Chapter 6 Growth Factors in Adult Stem Cell-BasedSkeletal Tissue Engineering -- 6.1 Introduction -- 6.1.1 Developmental Biology of Skeletogenic Growth Factors -- 6.1.2 Complexity in Growth Factor-Mediated Mesenchymal Stem Cell Differentiation -- 6.2 Discovery and Biology of Growth Factors, Hormones, and Nutrients -- 6.2.1 Growth Factors -- 6.2.1.1 Insulin-Like Growth Factors -- 6.2.1.2 Transforming Growth Factors-β -- 6.2.1.3 Bone Morphogenetic Proteins -- 6.2.1.4 Fibroblast Growth Factors -- 6.2.1.5 Platelet-Derived Growth Factors -- 6.2.1.6 Bone-Derived Growth Factors -- 6.2.2 Hormones -- 6.2.2.1 1,25-Dihydroxyvitamin D3 -- 6.2.2.2 Glucocorticoids -- 6.2.2.3 Parathyroid Hormone and Parathyroid Hormone-Related Peptide -- 6.2.3 Nutrients -- 6.2.3.1 Ascorbic Acid -- 6.2.3.2 β-Glycerophosphate -- 6.3 Growth Factors in Appendicular Skeletal Repair -- 6.3.1 Insulin-Like Growth Factors -- 6.3.1.1 IGFs in Osteogenesis -- 6.3.1.2 IGFs in Chondrogenesis -- 6.3.2 Transforming Growth Factors-β -- 6.3.2.1 TGF-βs in Osteogenesis -- 6.3.2.2 TGF-βs in Chondrogenesis -- 6.3.3 Bone Morphogenetic Proteins -- 6.3.3.1 BMPs in Osteogenesis -- 6.3.3.2 BMPs in Chondrogenesis -- 6.3.4 Growth Differentiation Factors in Osteogenesis and Chondrogenesis -- 6.3.5 Fibroblast Growth Factors -- 6.3.5.1 FGFs in Osteogenesis -- 6.3.5.2 FGFs in Chondrogenesis -- 6.3.6 Platelet-Derived Growth Factors -- 6.3.7 1,25-Dihydroxy Vitamin D3.

6.3.8 Dexamethasone -- 6.3.8.1 DEX in Osteogenesis -- 6.3.8.2 DEX in Chondrogenesis -- 6.3.9 Parathyroid Hormone-Related Peptide -- 6.4 Growth Factors in Craniofacial Skeletal Repair -- 6.4.1 Growth Factors in Cranial Osteogenesis -- 6.4.2 Growth Factors in Mandibular Repair -- 6.4.3 Growth Factors in TMJ Repair -- 6.4.4 Growth Factors in Periodontium Regeneration -- 6.5 Conclusion -- Acknowledgments -- References -- Chapter 7 Translational Approaches for EngineeringBone Repair -- 7.1 Introduction -- 7.2 Bone Repair Scaffolds -- 7.3 Cell-Based Strategies -- 7.4 Protein Delivery -- 7.5 Gene Therapy -- 7.6 Preclinical Testing -- 7.7 Conclusions and Future Directions -- References -- Chapter 8 Translational Approaches in Cartilage and Synovial Joint Regeneration -- 8.1 Introduction -- 8.2 Synovial Joint Anatomy and Function -- 8.3 Current Clinical Treatments of Cartilage Degeneration and Osteoarthritis -- 8.4 Earlier Findings of Engineering the Entire Synovial Joint Condyle -- 8.5 Nanofibers as Scaffold Reinforcement Materials for Cartilage Regeneration -- 8.6 Synergistic Actions of Hematopoietic and Mesenchymal Cell Lineages for Bone Regeneration -- 8.7 Challenges and Strategies of Cartilage Regeneration and Synovial Joint Bioengineering -- Acknowledgments -- References -- Chapter 9 Functional Tissue Engineering of Ligament and Tendon Injuries -- 9.1 Introduction -- 9.2 Normal Ligaments and Tendons -- 9.3 Healing of Ligaments and Tendons -- 9.3.1 Medial Collateral Ligament of the Knee -- 9.3.2 Anterior Cruciate Ligament Reconstruction -- 9.4 Application of Functional Tissue Engineering -- 9.4.1 Growth Factors -- 9.4.2 Gene Therapy -- 9.4.3 Cell Therapy -- 9.4.4 Biological Scaffolds -- 9.4.5 Improvement of Bioscaffolds via Cell Seeding and Mechanical Stimulation -- 9.5 Summary and Future Directions -- Acknowledgments -- References.

Chapter 10 Dental and Craniofacial Tissue Engineering -- 10.1 Introduction -- 10.2 Recent Breakthroughs in Dental Tissue Engineering Research -- 10.2.1 Whole Tooth Tissue Engineering -- 10.2.2 Reparative Dentin -- 10.2.3 Periodontal Ligament Guided Tissue Formation -- 10.2.4 Characterizations of Epithelial Dental Stem Cells -- 10.2.5 Mesenchymal Dental Stem Cell Characterizations -- 10.2.6 Scaffold Materials and Fabrication for Dental Tissue Engineering Applications -- 10.2.7 Characterization of Human Supernumerary Tooth Phenotypes -- 10.3 Current Obstacles to Dental Tissue Engineering Applications -- 10.3.1 Identification and Utilization of Suitable Stem Cell Sources for Dental Tissue Engineering Applications -- 10.3.2 Cryopreservation of Deciduous Tooth Pulp and Wisdom Tooth Tissues -- 10.3.3 Generating Functional Bioengineered Whole Teeth of Predetermined Size and Shape -- 10.3.4 Functional Bioengineered Tooth Roots -- 10.4 The Future of Tooth Tissue Engineering -- 10.4.1 Guided Dental Tissue Engineering Strategies -- Acknowledgments -- References -- Chapter 11 Neural Tissue Engineering: Fundamental and Translational Approaches -- 11.1 Nerve Injuries -- 11.2 Neural Tissue Engineering Device Design -- 11.2.1 Biomaterials in Neural Tissue Engineering -- 11.3 Fundamental Guidance Approaches for Translational Application -- 11.3.1 Physical Guidance -- 11.3.2 Chemical Guidance -- 11.3.3 Cell-Based Therapies and Cell Delivery -- 11.4 Progress and Future Challenges -- References -- Chapter 12 Bioengineered Soft Tissue for Plastic and Reconstructive Surgeries -- 12.1 Deficiencies of Current Materials for Soft Tissue Reconstruction and Augmentation -- 12.2 Anatomic Basis of Soft Tissue: Breast, Skin, and Subcutaneous Soft Tissue -- 12.2.2 Skin -- 12.2.1 Breast -- 12.3 Shape and Dimensions Are Critical for Reconstructive and Plastic Surgeries.

12.4 Design Approaches for Engineered Soft Tissue -- 12.4.1 Acellular Approaches -- 12.4.1.1 Facial Fillers -- 12.4.1.2 Breast Reconstruction -- 12.4.1.3 Biomaterials and Growth Factors -- 12.4.2 Cell-Based Approaches -- 12.4.2.1 Skin and Facial Rejuvenation Using Autologous Cells and Tissues -- 12.4.2.2 Breast Reconstruction and Augmentation -- 12.5 Conclusions -- Acknowledgments -- References -- Chapter 13 Bone Tissue Engineering -- 13.1 Health Relevance -- 13.2 Production of Bone Constructs -- 13.2.1 Embryonic Stem Cells Versus Adult Stem Cells -- 13.2.2 Mesenchymal Stem Cells -- 13.2.2.1 Obtaining and Characterizing Stem Cells -- 13.2.2.2 Immunological Properties of MSCs -- 13.3 Scaffolds for Tissue-Engineered Bone -- 13.3.1 Criteria for Optimal Scaffold Design -- 13.3.2 Critical Structural Properties of Scaffolds for Optimum Bone Ingrowth -- 13.3.2.1 Porosity -- 13.3.2.2 Topography and Surface Chemistry -- 13.3.2.3 Intrinsic Mechanical Properties -- 13.3.2.4 Scaffolds as Microenvironments for Bone Formation -- 13.4 Bioreactors -- 13.4.1 Limitations of Two-Dimensional Static Cell Culture Methods -- 13.4.2 Definition of a Bioreactor -- 13.4.3 Critical Issues in the Production of Bone Constructs in Bioreactors -- 13.4.3.1 Solving Mass Transfer Problems -- 13.4.3.2 Matrix Seeding Quality -- 13.4.3.3 Mastering the Mechanical Forces Applied -- 13.4.4 Choice of the Type of Bioreactor -- 13.5 Transplantation Studies -- 13.5.1 Cell Delivery in an Ischemic Environment -- 13.5.2 Orthotopic Assay -- 13.5.3 Fate and Role of Transplanted Cells -- 13.6 Conclusions -- Acknowledgments -- References -- Chapter 14 Critically Sized Bone Defects -- 14.1 Introduction -- 14.2 Critically Sized Defect -- 14.3 Animal Models of Calvarial Defects -- 14.3.1 Mouse -- 14.3.2 Rat -- 14.3.3 Rabbit -- 14.3.4 Dog -- 14.3.5 Guinea Pig -- 14.3.6 Pig.

14.3.7 Nonhuman Primate Species.