Cover -- Series page -- Title page -- Copyright page -- Contents -- Contributors -- Preface -- Introduction -- PART I: Engineering Bio-inspired Material Microenvironments -- CHAPTER 1: ECM-Inspired Chemical Cues: Biomimetic Molecules and Techniques of Immobilization -- 1.1 Introduction -- 1.2 Development and Immobilization of Biomimetic Cues in 3-D Biomaterials -- 1.2.1 Synthetic Peptides Derived from Fibronectin, Laminin, and Collagen -- 1.2.2 Carbohydrate-Binding Peptides -- 1.2.3 Glycomimetic Peptides -- 1.2.4 Growth Factors -- 1.3 Spatial Orientation and Dynamic Display -- 1.3.1 Spatially Controlled Display -- 1.3.2 Stimuli-Sensitive Dynamic Display -- 1.4 Future Perspectives -- References -- CHAPTER 2: Dynamic Materials Mimic Developmental and Disease Changes in Tissues -- 2.1 Introduction -- 2.2 Cell Scaffolds, Their Intrinsic Properties, and Their Effects on Cells -- 2.2.1 Natural Polymers and Their Properties -- 2.2.2 Synthetic Polymers and Their Properties -- 2.2.3 The Effects of Scaffolds on Cells -- 2.3 ECM is a Dynamic Tissue -- 2.4 Dynamic Scaffolds -- 2.4.1 Dynamically Stiffening Scaffolds -- 2.4.2 Degradable Scaffolds -- 2.5 Conclusion -- Acknowledgments -- References -- CHAPTER 3: The Role of Mechanical Cues in Regulating Cellular Activities and Guiding Tissue Development -- 3.1 Introduction -- 3.2 Mechanotransduction -- 3.2.1 Mechanotransduction from Extracellular Matrix to Cytoplasmic Structures -- 3.2.2 Mechanotransduction by Cell-ECM Adhesions -- 3.2.3 Mechanotransduction by Cell-Cell Adhesions -- 3.2.4 Intracellular Molecules -- 3.2.5 AdhesionMediated Signaling Pathways -- 3.3 Mechanotransduction from Cytoplasm to Nucleus -- 3.4 Role of Mechanical Cues in Developmental Biology -- 3.5 Applications of Mechanical Stimulation in Regenerative Medicine -- 3.5.1 Articular Cartilage -- 3.5.2 Tendon/Ligament -- 3.5.3 Bone.

3.5.4 Blood Vessels -- 3.6 Summary -- References -- CHAPTER 4: Contribution of Physical Forces on the Design of Biomimetic Tissue Substitutes -- 4.1 Introduction -- 4.1.1 Molecular Mechanisms of Cell Adhesion -- 4.1.2 Cell Adhesion to Substrates -- 4.2 Physical Forces -- 4.2.1 Mechanical Forces -- 4.2.2 Thermal Forces (NIPAM) -- 4.2.3 Electromagnetic Forces (Continuous, Pulsatile) -- 4.2.4 Hydrodynamic Forces (Shear -- Pulsatile, Compression -- Continuous) -- 4.3 Conclusion -- Acknowledgments -- References -- CHAPTER 5: Cellular Responses to Bio-Inspired Engineered Topography -- 5.1 Introduction -- 5.1.1 Historical Introduction to Cellular Responses to Physical Cues -- 5.1.2 Physical Cues in Nature -- 5.2 Definition of Engineered Topography -- 5.3 Surface Fabrication Techniques -- 5.3.1 Fabrication of Engineered Topography -- 5.4 Cellular Responses to 2-D Engineered Topographies -- 5.5 Cellular Responses to Dynamic, Engineered 2-D Topographies -- 5.6 Conclusions and Future Directions -- Acknowledgments -- References -- CHAPTER 6: Engineering the Mechanical and Growth Factor Signaling Roles of Fibronectin Fibrils -- 6.1 Introduction -- 6.2 Structure of Fibronectin -- 6.3 Assembly of Fibronectin Fibrils -- 6.4 Mechanics of Fibronectin Fibrils -- 6.5 Role of Fibronectin Fibrils in Cell Attachment -- 6.6 Role of Fibronectin Fibrils in Growth Factor Signaling -- 6.7 Cell-Free Mechanisms of Fibril Formation -- 6.8 Cell-Derived Fibronectin Matrices -- 6.9 Use of Fibronectin in Tissue Engineering Applications -- 6.10 Conclusions -- References -- CHAPTER 7: Biologic Scaffolds Composed of Extracellular Matrix as a Natural Material for Wound Healing -- 7.1 Introduction -- 7.2 Products and Clinical Use of ECM -- 7.3 Mechanisms of ECM Remodeling -- 7.3.1 Biologic Scaffold Degradation and Recruitment of Stem/Progenitor Cells.

7.3.2 The Effect of Site-Appropriate Mechanical Loading -- 7.3.3 Modulation of the Host Innate Immune Response Toward a Regulatory and Constructive Phenotype -- 7.4 Summary -- Acknowledgment -- References -- CHAPTER 8: Bio-Inspired Integration of Natural Materials -- 8.1 Introduction -- 8.1.1 Extracellular Matrix (ECM) Structure and Composition -- 8.1.2 Fundamentals of Scaffolding Using Naturally Derived Materials -- 8.2 Naturally Derived Materials -- 8.2.1 Animal Origin -- 8.2.2 Plant Origin -- 8.2.3 Algae Origin -- 8.2.4 Microbial Origin -- 8.3 Conclusions -- Acknowledgments -- References -- PART II: Bio-Inspired Tissue Engineering -- CHAPTER 9: Bio-Inspired Design of Skin Replacement Therapies -- 9.1 Introduction -- 9.2 Bio-Inspiration of Skin Replacement Therapy -- 9.2.1 Observations -- 9.3 Biomimetic Solutions -- 9.3.1 Epidermal Replacement: Epicell® (Genzyme Tissue Repair) -- 9.3.2 Treatment of Chronic Wounds: Apligraf® (Organogenesis) -- 9.3.3 Dermal Regeneration: Integra® -- 9.4 Discussion -- References -- CHAPTER 10: Epithelial Engineering: From Sheets to Branched Tubes -- 10.1 Introduction -- 10.2 Inspiration from the Biology of Epithelial Morphogenesis -- 10.2.1 Collective Migration of Epithelial Sheets -- 10.2.2 Folding of Epithelial Sheets -- 10.2.3 Tubulogenesis -- 10.2.4 Branching Morphogenesis -- 10.3 Engineering Approaches to Mimic Epithelial Morphogenesis -- 10.3.1 Making a Sheet -- 10.3.2 Folding a Sheet -- 10.3.3 Making a Tube -- 10.3.4 Making a Branch -- 10.4 Conclusion -- Acknowledgments -- References -- CHAPTER 11: A Biomimetic Approach toward the Fabrication of Epithelial-like Tissue -- 11.1 Introduction -- 11.2 Skin ECM and Its Function -- 11.3 Skin Tissue Engineering and Scaffold Design -- 11.3.1 Particle Leaching Technique -- 11.3.2 Emulsion Freeze-Drying -- 11.3.3 High-Pressure Gas Expansion Methods.

11.3.4 Phase Separation Method -- 11.3.5 Electrospinning Technique -- 11.4 Biomimetic Approach toward the Formation of Epithelial-Like Tissue Using Electrospun Nanofibers -- 11.4.1 Incorporation of ECM Components into Electrospun Nanofibers -- 11.4.2 On-Site Layer-by-Layer Cell Assembly Approach for 3-D Tissue Formation -- 11.4.3 Formation of 3-D Epithelial-Like Tissues -- 11.5 Future Perspective and Challenge -- 11.6 Conclusion -- References -- CHAPTER 12: Nano- and Microstructured ECM and Biomimetic Scaffolds for Cardiac Tissue Engineering -- 12.1 Introduction -- 12.2 Structure and Function of the Myocardium -- 12.2.1 Multiscale Hierarchy of the Contractile Apparatus -- 12.2.2 Mechanical Anisotropy -- 12.2.3 Innervation and the Conduction System -- 12.2.4 Vascularization -- 12.2.5 Extracellular Matrix -- 12.3 Bio-inspired Design Requirements of Cardiac Tissue Engineering Scaffolds -- 12.4 Approaches to Fabricating ECM Biomimetic Scaffolds -- 12.4.1 Porous Scaffolds -- 12.4.2 Micro- and Nanofiber Scaffolds -- 12.4.3 Synthetic and Naturally Derived Hydrogels -- 12.4.4 Nano- and Microfabricated Scaffolds -- 12.4.5 Cell-Generated ECM Scaffolds -- 12.4.6 Decellularized ECM Scaffolds -- 12.5 Persistent Challenges -- 12.5.1 Cell Sources for Cardiomyocytes -- 12.5.2 Vascularization -- 12.6 The Future of Cardiac Tissue Engineering -- References -- CHAPTER 13: Strategies and Challenges for Bio-inspired Cardiovascular Biomaterials -- 13.1 Need for Cardiovascular Biomaterials -- 13.1.1 Cardiovascular Tissue Regeneration -- 13.1.2 Unmet Clinical Need: Incidence and Prevalence of Cardiovascular Disease -- 13.1.3 Need for Tissue-Engineered Solutions -- 13.2 Structure Equals Function: Focus on Strategies that Introduce Hierarchical Organization -- 13.2.1 Tissue Engineering Tools -- 13.2.2 Hierarchical Structure of the Heart and Blood Vessels.

13.3 Tissue Engineering Approaches to Cardiovascular Biomaterials -- 13.3.1 Scaffolds: Foundational Architecture and Mechanical Properties -- 13.3.2 Bioreactors and Bioactive Molecules: Active Exogenous Forces -- 13.3.3 Cell Sources: Cell Phenotype and Secreted Extracellular Matrix -- 13.4 Scaffold-Free Tissue Engineering: 3-D Tissues Without Exogenous Material Complications -- 13.5 Conclusion -- Acknowledgments -- References -- CHAPTER 14: Evaluation of Bio-inspired Materials for Mineralized Tissue Regeneration Using Type I Collagen Reporter Cells -- 14.1 Introduction -- 14.2 Collagen 1 Promoter/GFP Reporter Technology -- 14.2.1 Reporter Gene Systems -- 14.2.2 How to Make a Reporter Gene System -- 14.3 Primary Cell Harvest and Image Analysis of the Collagen Reporter Cells from Transgenic Mice -- 14.3.1 Harvesting Primary Osteoprogenitor Cells From Transgenic Mice Calvarium -- 14.3.2 In Vitro Imaging and Analysis -- 14.4 Type I Collagen/GFP Reporter System with Human Cells -- 14.5 Evaluation of Biomimetic cHA Thin Films by Collagen/GFP Reporter Cells -- 14.5.1 Biomedical and Clinical Applications of Carbonated Hydroxyapatite -- 14.5.2 Synthesis and Characterization of Thin Films of Carbonated Hydroxyapatite -- 14.5.3 Assessment of Osteogenic Properties of cHA Thin Films Using Primary Type I Collagen/GFP Reporter Cells -- 14.6 Evaluation of Fibrillar Collagen Thin Films by Primary Type I Collagen/GFP Reporter Cells -- 14.6.1 Biomedical and Clinical Applications of Fibrillar Collagen -- 14.6.2 Synthesis and Characterization of Fibrillar Thin Films of Collagen -- 14.6.3 Results of Type I Collagen/GFP Reporter Cells Technology Applied to Fibrillar Collagen Films -- 14.7 In vivo Use of Type I Collagen/GFP Reporter Mice to Screen Biomimetic Collagen/Hydroxyapatite Scaffolds -- 14.7.1 Biomedical and Clinical Applications of Collagen/Apatite Scaffolds.

14.7.2 Synthesis and Characterization of the Collagen/Apatite Scaffolds.