Organ Tissue Engineering

Description

Provides a concise overview of organ tissue engineering Analyzes the current state, issues, and key challenges Details desired outcomes with a focus on functional readouts The notion of being able to engineer complete organs has inspired an entire generation of researchers. While recent years have brought significant progress in regenerative medicine and tissue engineering, the immense challenges encountered when trying to engineer an entire organ have to be acknowledged. Despite a good understanding of cell phenotypes, cellular niches and cell-to-biomaterial interactions, the formation of tissues composed of multiple cells remains highly challenging. Only a step-by-step approach will allow the future production of a living tissue construct ready for implantation and to augment organ function. In this book, expert authors present the current state of this approach. It offers a concise overview and serves as a great starting point for anyone interested in the application of tissue engineering or regenerative medicine for organ engineering. Each chapter contains a short overview including physiological and pathological changes as well as the current clinical need. The potential cell sources and suitable biomaterials for each organ type are discussed and possibilities to produce organ-like structures are illustrated. The ultimate goal is for the generated small tissues to unfold their full potential in vivo and to serve as a native tissue equivalent. By integrating and evolving, these implants will form functional tissue in-vivo. This book discusses the desired outcome by focusing on well-defined functional readouts. Each chapter addresses the status of clinical translations and closes with the discussion of current bottlenecks and an outlook for the coming years. A successful regenerative medicine approach could solve organ shortage by providing biological substitutes for clinical use - clearly, this merits a collaborative effort. Preface Contents About the Editors Contributors Part I: Circulatory and Respiratory Systems Bioinspired Vascular Grafts 1 Introduction 2 Structural Considerations 2.1 Structural Proteins: Collagen and Elastin 2.2 Cellular Components: Endothelial Cells, Smooth Muscle Cells, and Adventitial Fibroblasts 2.3 Structural Considerations in Vascular Grafts 3 Mechanical Considerations 3.1 Hyperelasticity and Compliance 3.2 Residual Stress 3.3 Mechanical Considerations in Vascular Grafts 4 Biological Considerations 4.1 Smooth Muscle Cell Phenotype 4.2 Endothelial Cell Phenotype 4.3 Adventitial Fibroblast Phenotype 4.4 Biological Considerations in Vascular Grafts 5 Conclusions References Heart Valve Bioengineering 1 Introduction 2 Cardiac Valve Anatomy and Functionality 2.1 Valve Anatomy and Functionality 2.1.1 Atrioventricular Valves 2.1.2 Semilunar Valves 2.2 Valve Cell and Tissue Composition 2.2.1 Tissue Structure 2.2.2 Cell Composition 2.3 Cellular Mechanisms of Valvular Disease 3 Heart Valve Pathology 3.1 Valve Stenosis 3.2 Valve Insufficiency 4 Current Treatment Options for Valvular Disease 4.1 Valve Repair 4.2 Valve Replacement 4.3 Heart Valve Prostheses Options 4.3.1 Mechanical Valve Prostheses: A Durable Solution 4.3.2 Homografts: A Promising Native-Like Alternative 4.3.3 Xenogeneic Bioprosthetic Valves: An Alternative to Homografts and Mechanical Valves 4.3.4 Non-resorbable Polymeric Valves: A Cost-Effective Solution 4.4 Clinical Impact and Burden on Society 5 Heart Valve Tissue Engineering 5.1 In Vitro Heart Valve Tissue Engineering 5.2 In-Body Heart Valve Tissue Engineering 5.3 In Situ Heart Valve Tissue Engineering 6 Scaffolds for Heart Valve Tissue Engineering 6.1 Native Tissue-Derived Scaffolds 6.1.1 Decellularized Homografts 6.1.2 Decellularized Xenografts 6.2 In Vitro-Derived TEM-Based Scaffolds 6.3 Bioresorbable Polymeric Scaffolds 6.3.1 Bioresorbable Synthetic Polymeric Scaffolds 6.3.2 Autologous Cell Pre-seeding onto Bioresorbable Polymeric TEHVs 6.3.3 Hybrid Polymeric Scaffolds 7 Testing of Tissue-Engineered Heart Valves 7.1 In Silico Models to Optimize Valve Design 7.1.1 Design Optimization for Artificial Heart Valve Replacements 7.1.2 Design Optimization for Tissue-Engineered Heart Valves 7.2 In Vitro Models to Test Valve Functionality 7.2.1 Pulse Duplicator Systems 7.2.2 Durability Systems 7.2.3 Cardiac Biosimulator and Beating Heart Platforms 7.3 In Vivo Animal Models to Assess Remodeling 7.3.1 Nonhuman Primate Model 7.3.2 Swine Model 7.3.3 Ovine Model 8 Challenges Toward Clinical Translation 8.1 Regulatory Challenges 8.2 Logistical Challenges 8.3 Clinical Requirements 9 Conclusions References Cell Sheets for Cardiac Tissue Engineering 1 Introduction 2 Myocardial Regenerative Therapy 3 Scaffold-Based Engineering of Cardiac Tissue 4 Cell Sheet-Based Tissue Engineering for the Generation of Cardiac Tissue 5 Transplantation of Cardiac Patches onto Ischemic Hearts 6 Effects of Cell Sheet Transplantation in Infant Ischemic Hearts 7 Vascularization of Engineered Myocardial Tissue for Scaling-Up of Tissue Size 8 Organ-Like Tissue Fabrication 9 Scaffold-Based Cardiac Pumps 10 Cell Sheet-Based Cardiac Pump 11 Future Perspectives 12 Conclusions References Bioengineering of Trachea and Esophagus 1 Introduction 2 Tracheal Bioengineering 2.1 Introduction 2.2 Anatomy and Embryology 2.3 Strategy for Tissue Engineering 2.4 Scaffolds 2.5 Cells 2.6 Animal Models 2.7 Clinical Trials 2.8 Conclusion 3 Esophageal Bioengineering 3.1 Introduction 3.2 Anatomy, Physiology, and Development 3.3 Strategy and Challenges for Esophageal Tissue Engineering 3.4 Scaffold 3.4.1 Synthetic Scaffolds 3.4.2 Natural Scaffolds 3.4.3 Composite/Hybrid Scaffolds 3.5 Cells 3.5.1 Epithelial Cells Smooth and Skeletal Muscle Progenitors Mesoangioblasts (MABs) Mesenchymal Stem/Stromal Cells (MSCs) 3.5.2 Neural Progenitors 3.6 Clinical Trials 3.6.1 Partial Thickness Defects Full Thickness Defects - Patch Full Thickness Defects - Circumferential 3.7 Conclusions 4 Final Considerations References Part II: Digestive and Exocrine Systems Liver Tissue Engineering 1 Introduction 1.1 Brief Description of Acute, Inborn Errors of Metabolism and End-Stage Liver Disease Worldwide 1.2 Liver Transplant Worldwide 1.3 Bottlenecks and Limitations 1.4 Solutions Developed Throughout the Years to Increase Organ Availability 2 Tissue Engineering 2.1 First Approaches Used for Liver Tissue Engineering 2.2 Whole-Liver Scaffolds (Decellularization) 2.3 Cellular Components, Their Source, and Role in Generating Hepatic Tissue 2.4 Bioreactors for Liver Tissue Engineering 2.5 In Vivo Results of Liver Tissue-Engineered Constructs 3 Future Perspectives 3.1 Liver Organoids 3.2 Liver Buds 3.3 3D Bioprinting 4 Regulatory Landscape for Tissue-Engineered Livers 4.1 Food and Drug Administration (FDA) 4.2 European Medicines Agency (EMA) 4.3 Ministry of Health, Labour, and Welfare (MHLW) 5 Conclusions References Bioprinting Strategies to Engineer Functional Salivary Gland Organoids 1 Introduction 2 Organotypic Three-Dimensional (3D) Cell Culture System 2.1 Overview of 3D Cell Culture Systems 2.2 Spheroid 3D Culture Systems 2.3 Potential Cell Sources for Salivary Gland Tissue Engineering 2.3.1 Salivary Gland Stem/Progenitor Cells 2.3.2 Bone Marrow-Derived Mesenchymal Stem Cells (BM-MSC) 2.3.3 Adipose-Derived Stem Cells 2.3.4 Dental Pulp Stem Cells 3 Incorporating Different Biomaterials for Salivary Gland Bioengineering 4 3D Bioprinting 4.1 Magnetic-Based Bioprinting 4.2 Magnetic Levitation and 3D Bioassembly 4.3 Scaffold-Assisted Bioprinting 5 Conclusions References Tissue-Engineered Thymus 1 Introduction 2 Structure and Function of the Thymus 2.1 Structure and Histology 2.2 Function 3 Embryology and Development 4 Thymus Dysfunction and Damage 4.1 Thymus Involution 4.2 Infection 4.3 Cytoablative Therapies 4.4 Graft-Versus-Host Disease 5 Endogenous Thymus Regeneration 6 Exogenous Thymus Regeneration 6.1 Use of Cytokines and Growth Factors 6.2 Use of Stem Cells, Progenitor Cells, and Induced Pluripotent Stem Cells 6.3 Targeting Cellular Pathways Within the Thymus 6.4 External Modulation of T-Cell Response Within the Thymus 6.5 Thymus Transplantation 6.6 Artificial Thymopoietic Environments 7 Thymus Bioengineering 8 Current Challenges 9 Conclusions References Part III: Excretory and Respiratory Systems Tissue-Engineered Renal Tissue 1 Introduction 2 Renal Tissue Engineering: Foundational Knowledge 3 Potential Cell Sources for Scaffold Seeding 4 Tissue Construct Template Materials 5 Vascularization 6 Conclusions References Engineering of the Bladder and Urethra 1 Introduction 2 Engineering Strategies for Bladder and Urethra 3 Vascularization 4 Bioreactors 5 Biomaterials for Bladder and Urethra 6 Decellularized Matrices 7 Natural Polymers 8 Synthetic Biomaterials 9 Smart and Hybrid Polymers 10 Cells for Engineering Bladder and Urethra 10.1 Somatic Cells 10.2 Stem Cells 11 Applications of Bladder and Urethra 12 Conclusions References Tissue-Engineered Ovary 1 Introduction 1.1 Causes of Premature Ovarian Insufficiency 1.2 Recognition of the Problem 1.3 Beyond Fertility 2 Current State of Restoring Ovarian Function 2.1 Ovarian Tissue Cryopreservation (OTC) and Transplantation 2.2 Location of Transplantation 2.3 In Situ Options for Fertility 3 Important Features in an Ovary to Be Recreated 3.1 Oocytes 3.2 Support Cells and Folliculogenesis 3.3 Hormones 3.4 Vascularization 3.5 Compartmentalization and Physical Features 4 Materials Used for Engineered Ovaries 4.1 Overarching Consideration for Engineering an Ovary 4.2 Restoration of Ovarian Hormones 4.3 Encapsulation Methods to Restore Ovarian Function 4.4 Scaffold Development for Ovarian Restoration 4.5 In Vitro Studies with Human Follicles 5 Conclusions References Tissue-Engineered Approaches for Penile Reconstruction 1 Introduction 1.1 Anatomy and Physiology of Penis 1.2 History of Tissue-Engineered Penile Reconstruction 2 Corpus Cavernosum 3 Penile Prosthesis 4 Tunica Albuginea 5 Penile Augmentation 6 Recent Novel Technics 6.1 Cell Therapy and Stem Cell Therapy in ED 6.2 Gene Therapy for ED 6.3 Bioprinting 7 Conclusions References Part IV: Musculoskeletal System Injectable Calcium Phosphate Cements for the Reconstruction/Repair of Oral and Cranio-maxillofacial Bone Defects: Clinical Out... 1 Introduction 2 Etiology of Bone Defects in the Oral and Cranio-maxillofacial Region 2.1 Repair of Intrabony Defects Caused by Periodontitis 2.2 Preservation of the Alveolar Volume After Tooth Extraction/Extraction Socket Management 2.3 Reconstruction of an Atrophic Alveolar Ridge 2.4 Reconstruction of Large Defects Caused by Trauma or Traumatic Therapy 2.5 Cosmetic Surgery for Developmental/Congenital Diseases at the Cranio-maxillofacial Region 3 Injectable CPCs for Reconstruction/Repair of the Oral and Cranio-maxillofacial Region 4 Clinical Outcome of CPCs in Reconstruction of the Oral and Cranio-maxillofacial Region 4.1 Reconstruction of Periodontal Intrabony Defects 4.2 Extraction Socket Management 4.3 Augmentation of the Maxillary Sinus 4.4 Augmentation of the Atrophic Mandible Alveolar Ridge 4.5 Reconstruction of the Craniofacial Region 5 Conclusion and Outlook References Tissue-Engineered Teeth 1 Introduction 2 Natural Tooth Development 2.1 Morphogenesis of the Tooth Crown 2.1.1 Cells and Signaling Pathways During Tooth Development BMP Signaling Shh Signaling WNT Signaling FGF Signaling EDA Signaling 2.2 Tooth Root Development 2.2.1 Tooth Root Morphogenesis 2.2.2 Tooth Root Development Signaling Pathways 3 Cells and Scaffolds 3.1 Dental Stem Cells 3.1.1 Dental Pulp Stem Cells: DPSCs 3.1.2 Periodontal Ligament Stem Cells: PDLSCs 3.1.3 Stem Cells of the Apical Papilla: SCAPs 3.1.4 Follicle Stem Cells: DFCs 3.1.5 Induced Pluripotent Stem Cells: iPSCs 3.2 Cell Transplantation and Cell Homing 3.3 Scaffold Fabrication 3.3.1 Innovative and Advanced Scaffolds 3.3.2 The Use of 3D Printing for Tooth Tissue Engineering 4 Tooth Regeneration 4.1 Partial Tooth Regeneration 4.1.1 Dentin-Pulp Complex Regeneration 4.1.2 Periodontal Bone-PDL-Cementum Complex Regeneration Alveolar Bone Regeneration PDL-Cementum Complex Regeneration 4.1.3 Tooth Root Regeneration and Bio-root Engineering 4.2 Whole Tooth Regeneration 4.2.1 Scaffold-Based Methods for Whole Tooth Regeneration 4.2.2 Scaffold-Free Methods for Whole Tooth Regeneration 5 Conclusions References Generation of Ear Cartilage for Auricular Reconstruction 1 Introduction 2 Traditional Approaches for Auricular Reconstruction 3 Tissue Engineering Approach for Auricular Reconstruction 3.1 Seed Cell Sources for Auricular Regeneration 3.1.1 Chondrocytes 3.1.2 Mesenchymal Stem Cells 3.1.3 Co-culture of Chondrocytes with MSCs 3.1.4 Pluripotent Stem Cells 3.2 Scaffolds for Auricular Cartilage Regeneration 3.2.1 Synthetic Polymers as Scaffolds for Auricular Cartilage Engineering 3.2.2 Nature-Derived Materials as Scaffolds for Auricular Cartilage Engineering 3.2.3 Combined Application of Materials as Scaffold for Auricular Cartilage Engineering 3.3 3D Printing for Auricular Cartilage Engineering 3.4 In Vitro Generation of Human Ear-Shaped Cartilage 3.4.1 In Vitro Biochemical Stimuli 3.4.2 Mechanical Stimuli in the In Vitro Culture Condition 3.4.3 Oxygen Tension 3.4.4 In Vitro Culture Duration 3.5 In Vivo and Preclinical Evaluations 3.6 Clinical Translation of Tissue-Engineered Cartilage for Auricular Reconstruction 4 Conclusions References Stem Cell-Based and Tissue Engineering Approaches for Skeletal Muscle Repair 1 Introduction 2 Cell Replacement Therapy for the Treatment of Muscle Disorders 2.1 Myoblast Transplantation for the Treatment of Duchenne Muscular Dystrophy 2.2 Addressing Translational Roadblocks for Myoblast Transplantation 2.3 Clinical Procedures Involving Autologous Myoblast Transplantation 2.4 Further Considerations for Improvement of Myoblast Transplantation 3 Engraftment of Freshly Isolated Satellite Cells for Muscle Regeneration 4 Generation of Myogenic Precursors from Pluripotent Stem Cells 5 Direct Reprogramming of Somatic Cells into Myogenic Progenitors 6 Maintaining Satellite Cell Potency In Vitro 6.1 Basement Membrane Proteins that Support an Undifferentiated Satellite Cell State 6.2 Inhibition of Satellite Cell Differentiation by Small Molecules, Ligands, and Cytokines 6.3 Genetic Alteration that Support Satellite Cell Self-Renewal and Regeneration 7 Enhancing Muscle Stem Cell Engraftment Using Biomaterials 8 Stem Cell-Based Approaches to Engineer Skeletal Muscle Tissue 8.1 Engineering Skeletal Muscle Tissue In Vitro Using Myogenic Precursors 8.2 Vascularization of Skeletal Muscle Tissue Constructs 8.3 Innervation of Skeletal Muscle Tissue Constructs 8.4 Integrative Tissue Engineering Approaches to Treat VML 9 Conclusions References Ligament Tissue Engineering: The Anterior Cruciate Ligament 1 Introduction 2 Scaffolds for ACL Regeneration 3 Cell Sources for ACL Regeneration 4 Growth Factors and Gene Therapy 5 Mechanical Stimulation in ACL Regeneration 6 Future Directions in ACL Regeneration 7 Conclusions References Multiscale Multifactorial Approaches for Engineering Tendon Substitutes 1 Introduction 2 Tendon Injuries and Repair Mechanisms 3 Mechanoregulation Mechanisms 4 Tendon Tissue Engineering 4.1 Challenges of Cell-Based Approaches 4.2 Biomaterial Approaches for Tendon Tissue Engineering 4.2.1 Fibrous Scaffolds for Tendon Tissue Engineering Strategies Involving Topographic Cues Strategies Involving Mechanical Stimulation 4.2.2 3D Printing for Tendon Tissue Engineering 4.3 Role of Biological Cues in Tendon Tissue Engineering Strategies 4.3.1 Strategies Involving Medium Supplementation with Growth Factors 4.3.2 Biofunctionalization of Scaffolds with Growth Factors 4.3.3 Biofunctionalization of Scaffolds with ECM Components 5 Conclusions References Meniscus Regeneration Strategies 1 Introduction 2 Clinical Aspects 2.1 Endogenous Repair Cells in Case of a Meniscus Injury 2.2 Meniscus Reconstruction Improves the Knee Function in Long-Term 2.3 Prevention of Osteoarthritis by Meniscus Suturing in Long-Term 2.4 Stimulation of the Regenerative Potential of the Meniscus Tissue 3 Meniscus Tissue Engineering 3.1 Cell Sources 3.1.1 Stem Cells 3.1.2 Mesenchymal Stem Cells Bone Marrow Derived Stem Cells Synoviocytes Adipose Tissue-Derived Stem Cells Meniscus-Derived Stem Cells Cartilage-Derived Stem Cells 3.2 Mature Cells 3.2.1 Meniscus Fibrochondrocytes 3.2.2 Articular Chondrocytes 4 Biomaterials for Meniscus Tissue Engineering 4.1 Acellular Biomaterials 4.2 Clinical Use of Cell-Free Scaffolds 4.3 Scaffolds for Cell-Based Meniscus Therapy - Preclinical 5 Potential Ways for Healing Enhancement by Suture Augmentation 5.1 Augmentation of Meniscus Suture with Mesenchymal Stem Cells 5.2 Regeneration of Large-Size Meniscus Defects 5.3 Growth Factors 5.4 Gene Transfer 5.5 Animal Models for Tissue Engineering of Meniscus 5.6 3D Printing 6 Conclusions References Part V: Ocular System Bioengineered Corneas Entering the Clinical Realm 1 Introduction 1.1 The Human Cornea and Corneal Blindness 1.2 Corneal Transplantation and Challenges 1.2.1 Risk Factors Defining High-Risk Corneal Transplantation 1.3 Alloimmune Corneal Graft Rejection 1.4 Limitations to Human Corneal Transplantation 1.5 Potential of Bioengineered Corneas 2 Cell-Based Implants 2.1 Bioengineered Corneal Epithelium 2.2 Bioengineered Corneal Endothelium 2.3 Bioengineered Corneal Stroma 2.4 Bioengineered Multilayered Corneal Replacements 3 Keratoprostheses 3.1 Recent Advances in Keratoprosthes is Design for Improved Bio-integration 4 Cell-Free Pro-Regeneration Corneal Implants 4.1 Decellularized Corneas 4.2 Recombinant Human Collagen Implants 4.3 Recombinant Human Collagen Implants for High-Risk Patients 4.4 Collagen-Like Peptides (CLPs) as Collagen Analogs 5 Bioengineered Corneal Constructs Incorporating Delivery Systems 6 From Bench to Bedside 7 Conclusions References Index