Ashutosh Tiwari is Secretary General, International Association of Advanced Materials; Chairman and Managing Director of Tekidag AB (Innotech); Associate Professor and Group Leader, Smart Materials and Biodevices at the world premier Biosensors and Bioelectronics Centre, IFM-Linköping University; Editor-in-Chief, Advanced Materials Letters; a materials chemist and docent in the Applied Physics with the specialization of Biosensors and Bioelectronics from Linköping University, Sweden. He has more than 100 peer-reviewed primary research publications in the field of materials science and nanotechnology and has edited/authored more than 35 books on advanced materials and technologyBora Garipcan teaches at Boðaziçi University, Turkey.Lokman Uzun is an Associate Professor at the Department of Chemistry, Biochemistry Division, Hacettepe University, Ankara, Turkey where he also received his PhD in 2008. He is the author of more than 75 articles in peer-review journals and is the Assistant Editor of Hacettepe’s Journal of Biology and Chemistry. He recently took up a fellowship with the Biosensors and Bioelectronics Centre, Linköping University, Sweden. His research interest is mainly in materials science, surface modification, affinity interaction, polymer science, especially molecularly imprinted polymers and their applications in biosensors, bioseparation, food safety, and the environmental sciences.

• Preface xv1 Extracellular Matrix Proteins for Stem Cell Fate 1Betül Çelebi-Saltik1.1 Human Stem Cells, Sources, and Niches 21.2 Role of Extrinsic and Intrinsic Factors 51.2.1 Shape 51.2.2 Topography Regulates Cell Fate 61.2.3 Stiffness and Stress 61.2.4 Integrins 71.2.5 Signaling via Integrins 91.3 Extracellular Matrix of the Mesenchyme: Human Bone Marrow 111.4 Biomimetic Peptides as Extracellular Matrix Proteins 13References 152 The Superficial Mechanical and Physical Properties of Matrix Microenvironment as Stem Cell Fate Regulator 23Mohsen Shahrousvand, Gity Mir Mohamad Sadeghi and Ali Salimi2.1 Introduction 242.2 Fabrication of the Microenvironments with Different Properties in Surfaces 252.3 Effects of Surface Topography on Stem Cell Behaviors 282.4 Role of Substrate Stiffness and Elasticity of Matrix on Cell Culture 312.5 Stem Cell Fate Induced by Matrix Stiffness and Its Mechanism 322.6 Competition/Compliance between Matrix Stiffness and Other Signals and Their Effect on Stem Cells Fate 332.7 Effects of Matrix Stiffness on Stem Cells in Two Dimensions versus Three Dimensions 342.8 Effects of External Mechanical Cues on Stem Cell Fate from Surface Interactions Perspective 342.9 Conclusions 35Acknowledgments 36References 363 Effects of Mechanotransduction on Stem Cell Behavior 43Bahar Bilgen and Sedat Odabas3.1 Introduction 433.2 The Concept of Mechanotransduction 453.3 The Mechanical Cues of Cell Differentiation and Tissue Formation on the Basis of Mechanotransduction 463.4 Mechanotransduction via External Forces 473.4.1 Mechanotransduction via Bioreactors 483.4.2 Mechanotransduction via Particle-based Systems 513.4.3 Mechanotransduction via Other External Forces 533.5 Mechanotransduction via Bioinspired Materials 543.6 Future Remarks and Conclusion 54Declaration of Interest 55References 554 Modulation of Stem Cells Behavior Through Bioactive Surfaces 65Eduardo D. Gomes, Rita C. Assunção-Silva, Nuno Sousax, Nuno A. Silva and António J. Salgado4.1 Lithography 664.2 Micro and Nanopatterning 704.3 Microfluidics 714.4 Electrospinning 714.5 Bottom-up/Top-down  Approaches 744.6 Substrates Chemical Modifications 754.6.1 Biomolecules Coatings 764.6.2 Peptide Grafting 774.7 Conclusion 78References 79Contents vii5 Influence of Controlled Micro- and Nanoengineered Environments on Stem Cell Fate 85Anna Lagunas, David Caballero and Josep Samitier5.1 Introduction to Engineered Environments for the Control of Stem Cell Differentiation 865.1.1 Stem Cells Niche In Vivo: A Highly Dynamic and Complex Environment 865.1.2 Mimicking the Stem Cells Niche In Vitro: Engineered Biomaterials 885.2 Mechanoregulation of Stem Cell Fate 895.2.1 From In Vivo to In Vitro: Influence of the Mechanical Environment on Stem Cell Fate 895.2.2 Regulation of Stem Cell Fate by Surface Roughness 905.2.3 Control of Stem Cell Differentiation by Micro- and Nanotopographic Surfaces 925.2.4 Physical Gradients for Regulating Stem Cell Fate 965.3 Controlled Surface Immobilization of Biochemical Stimuli for Stem Cell Differentiation 1005.3.1 Micro- and Nanopatterned Surfaces: Effect of Geometrical Constraint and Ligand Presentation at the Nanoscale 1005.3.2 Biochemical Gradients for Stem Cell Differentiation 1075.4 Three-dimensional Micro- and Nanoengineered Environments for Stem Cell Differentiation 1125.4.1 Three-dimensional Mechanoregulation of Stem Cell Fate 1135.4.2 Three-dimensional Biochemical Patterns for Stem Cell Differentiation 1195.5 Conclusions and Future Perspectives 122References 1226 Recent Advances in Nanostructured Polymeric Surface: Challenges and Frontiers in Stem Cells 141Ilaria Armentano, Samantha Mattioli, Francesco Morena, Chiara Argentati, Sabata Martino, Luigi Torre and Josè Maria Kenny6.1 Introduction 1426.2 Nanostructured Surface 1446.3 Stem Cell 1466.4 Stem Cell/Surface Interaction 1476.5 Microscopic Techniques Used in Estimating Stem Cell/Surface 1486.5.1 Fluorescence Microscopy 1486.5.2 Electron Microscopy 1496.5.3 Atomic Force Microscopy 1536.5.3.1 Instrument 1546.5.3.2 Cell Nanomechanical Motion 1566.5.3.3 Mechanical Properties 1566.6 Conclusions and Future Perspectives 158References 1587 Laser Surface Modification Techniques and Stem Cells  Applications 165Çağrı Kaan Akkan7.1 Introduction 1667.2 Fundamental Laser Optics for Surface Structuring 1667.2.1 Definitive Facts for Laser Surface Structuring 1677.2.1.1 Absorptivity and Reflectivity of the Laser Beam by the Material Surface 1677.2.1.2 Effect of the Incoming Laser Light Polarization 1687.2.1.3 Operation Mode of the Laser 1697.2.1.4 Beam Quality Factor 1707.2.1.5 Laser Pulse Energy/Power 1717.2.2 Ablation by Laser Pulses 1727.2.2.1 Focusing the Laser Beam 1727.2.2.2 Ablation Regime 1737.3 Methods for Laser Surface Structuring 1747.3.1 Physical Surface Modifications by Lasers 1747.3.1.1 Direct Structuring 1757.3.1.2 Beam Shaping Optics 1777.3.1.3 Direct Laser Interference Patterning 1807.3.2 Chemical Surface Modification by Lasers 1817.3.2.1 Pulsed Laser Deposition 1817.3.2.2 Laser Surface Alloying 1847.3.2.3 Laser Surface Oxidation and Nitriding 1867.4 Stem Cells and Laser-Modified Surfaces 1877.5 Conclusions 191References 1928 Plasma Polymer Deposition: A Versatile Tool for Stem Cell Research 197M. N. Macgregor-Ramiasa and K. Vasilev8.1 Introduction 1978.2 The Principle and Physics of Plasma Methods for Surface Modification 1998.2.1 Plasma Sputtering, Etching an Implantation 2008.2.2 Plasma Polymer Deposition 2018.3 Surface Properties Influencing Stem Cell Fate 2028.3.1 Plasma Methods for Tailored Surface Chemistry 2038.3.1.1 Oxygen-rich Surfaces 2048.3.1.2 Nitrogen-rich Surfaces 2088.3.1.3 Systematic Studies and Copolymers 2108.3.2 Plasma for Surface Topography 2118.3.3 Plasma for Surface Stiffness 2138.3.4 Plasma for Gradient Substrata 2158.3.5 Plasma and 3D Scaffolds 2188.4 New Trends and Outlook 2198.5 Conclusions 219References 2209 Three-dimensional Printing Approaches for the Treatment of Critical-sized Bone Defects 231Sara Salehi, Bilal A. Naved and Warren L. Grayson9.1 Background 2329.1.1 Treatment Approaches for Critical-sized Bone Defects 2329.1.2 History of the Application of 3D Printing to Medicine and Biology 2339.2 Overview of 3D Printing Technologies 2349.2.1 Laser-based Technologies 2359.2.1.1 Stereolithography 2359.2.1.2 Selective Laser Sintering 2369.2.1.3 Selective Laser Melting 2369.2.1.4 Electron Beam Melting 2379.2.1.5 Two-photon Polymerization 2379.2.2 Extrusion-based Technologies 2389.2.2.1 Fused Deposition Modeling 2389.2.2.2 Material Jetting 2389.2.3 Ink-based Technologies 2399.2.3.1 Inkjet 3D Printing 2399.2.3.2 Aerosol Jet Printing 2399.3 Surgical Guides and Models for Bone Reconstruction 2409.3.1 Laser-based Surgical Guides 2409.3.2 Extrusion-based Surgical Guides 2409.3.3 Ink-based Surgical Guides 2419.4 Three-dimensionally Printed Implants for Bone Substitution 2429.4.1 Laser-based Technologies for Metallic Bone Implants 2449.4.2 Extrusion-based Technologies for Bone Implants 2459.4.3 Ink-based Technologies for Bone Implants 2469.5 Scaffolds for Bone Regeneration 2469.5.1 Laser-based Printing for Regenerative Scaffolds 2479.5.2 Extrusion-based Printing for Regenerative Scaffolds 2479.5.3 Ink-based Printing for Regenerative Scaffolds 2499.5.4 Pre- and Postprocessing Techniques 2509.5.4.1 Preprocessing 2509.5.4.2 Postprocessing: Sintering 2569.5.4.3 Postprocessing: Functionalization 2569.6 Bioprinting 2579.7 Conclusion 262List of Abbreviation 263References 26410 Application of Bioreactor Concept and Modeling Techniques to Bone Regeneration and Augmentation Treatments 277Oscar A. Deccó and Jésica I. Zuchuat10.1 Bone Tissue Regeneration 27810.1.1 Proinflammatory Cytokines 27910.1.2 Transforming Growth Factor Beta 27910.1.3 Angiogenesis in Regeneration 28010.2 Actual Therapeutic Strategies and Concepts toObtain an Optimal Bone Quality and Quantity 28110.2.1 Guided Bone Regeneration Based on Cells 28210.2.1.1 Embryonic Stem Cells 28210.2.1.2 Adult Stem Cells 28210.2.1.3 Mesenchymal Stem Cells 28310.2.2 Guided Bone Regeneration Based on PRP and Growth Factors 28410.2.2.1 Bone Morphogenetic Proteins 28710.2.3 Guided Bone Regeneration Based on Barrier Membranes 28810.2.4 Guided Bone Regeneration Based on Scaffolds 29010.3 Bioreactors Employed for Tissue Engineering in Guided Bone Regeneration 29110.4 Bioreactor Concept in Guided Bone Regeneration and Tissue Engineering: In Vivo Application 29410.5 New Multidisciplinary Approaches Intended to Improve and Accelerate the Treatment of Injured and/or Diseased Bone 30310.5.1 Application of Bioreactor in Dentistry: Therapies for the Treatment of Maxillary Bone Defects 30410.5.2 Application of Bioreactor in Cases of Osteoporosis 30710.6 Computational Modeling: An Effective Tool to Predict Bone Ingrowth 310References 31111 Stem Cell-based Medicinal Products: Regulatory Perspectives 321DenizOzdil and Halil Murat Aydin11.1 Introduction 32111.2 Defining Stem Cell-based Medicinal Products 32311.3 Regional Regulatory Issues for Stem Cell Products 32611.4 Regulatory Systems for Stem Cell-based Technologies 32711.4.1 The US Regulatory System 32811.5 Stem Cell Technologies: The EuropeanRegulatory System 336References 34012 Substrates and Surfaces for Control of Pluripotent Stem Cell Fate and Function 341Akshaya Srinivasan, Yi-Chin Toh, Xian Jun Loh and Wei Seong Toh12.1 Introduction 34212.2 Pluripotent Stem Cells 34212.3 Substrates for Maintenance of Self-renewal and Pluripotency of PSCs 34412.3.1 Cellular Substrates 34412.3.2 Acellular Substrates 34512.3.2.1 Biological Matrices 34512.3.2.2 ECM Components 34812.3.2.3 Decellularized Matrices 35012.3.2.4 Cell Adhesion Molecules 35112.3.2.5 Synthetic Substrates 35212.4 Substrates for Promoting Differentiation of PSCs 35512.4.1 Cellular Substrates 35512.4.2 Acellular Substrates 35612.4.2.1 Biological Matrices 35612.4.2.2 ECM Components 35812.4.2.3 Decellularized Matrices 36212.4.2.4 Cell Adhesion Molecules 36312.4.2.5 Synthetic Substrates 36312.5 Conclusions 366Acknowledgments 367References 36713 Silk as a Natural Biopolymer for Tissue Engineering 379Ayşe Ak Can and Gamze Bölükbaşi Ateş13.1 Introduction 38013.2 SF as a Biomaterial 38313.2.1 Fibroin Hydrogels and Sponges 38413.2.2 Fibroin Films and Membranes 38613.2.3 Nonwoven and Woven Silk Scaffolds 38613.2.4 Silk Fibroin as a Bioactive Molecule Delivery 38613.3 Biomedical Applications of Silk-based Biomaterials 38713.3.1 Bone Tissue Engineering 38713.3.2 Cartilage Tissue Engineering 38913.3.3 Ligament and Tendon Tissue Engineering 39113.3.4 Cardiovascular Tissue Engineering 39113.3.5 Skin Tissue Engineering 39313.3.6 Other Applications of Silk Fibroin 39313.4 Conclusion and Future Directions 393References 39414 Applications of Biopolymer-based, Surface-modified Devices in Transplant Medicine and Tissue Engineering 399Ashim Malhotra, Gulnaz Javan and Shivani Soni14.1 Introduction to Cardiovascular Disease 40014.2 Need Assessment for Biopolymer-based Devices in Cardiovascular Therapeutics 40014.3 Emergence of Surface Modification Applications in Cardiovascular Sciences: A Historical Perspective 40114.4 Nitric Oxide Producing Biosurface Modification 40314.5 Surface Modification by Extracellular Matrix Protein Adherence 40414.6 The Role of Surface Modification in the Construction of Cardiac Prostheses 40514.7 Biopolymer-based Surface Modification of Materials Used in Bone Reconstruction 40614.8 The Use of Biopolymers in Nanotechnology 40914.8.1 Protein Nanoparticles 41014.8.1.1 Albumin-based Nanoparticles and Surface Modification 41114.8.1.2 Collagen-based Nanoparticles and Surface Modification 41214.8.1.3 Gelatin-based Nanoparticle Systems 41314.8.2 Polysaccharide-based Nanoparticle Systems 41314.8.2.1 The Use of Alginate for Surface Modifications 41314.8.2.2 The Use of Chitosan-based Nanoparticles and Chitosan-based Surface Modification 41414.8.2.3 The Use of Chitin-based Nanoparticles and Chitin-based Surface Modification 41614.8.2.4 The Use of Cellulose-based Nanoparticles and Cellulose-based Surface Modification 417References 41815 Stem Cell Behavior on Microenvironment Mimicked Surfaces  423M. Özgen Öztürk Öncel and Bora Garipcan15.1 Introduction 42415.2 Stem Cells 42515.2.1 Definition and Types 42515.2.1.1 Embryonic Stem Cells 42615.2.1.2 Adult Stem Cells 42615.2.1.3 Reprogramming and Induced Pluripotent Stem Cells 42715.2.2 Stem Cell Niche 42715.3 Stem Cells: Microenvironment Interactions 42815.3.1 Extracellular Matrix 42915.3.2 Signaling Factors 42915.3.3 Physicochemical Composition 43015.3.4 Mechanical Properties 43015.3.5 Cell–Cell Interactions 43115.4 Biomaterials as Stem Cell Microenvironments 43115.4.1 Surface Chemistry 43115.4.2 Surface Hydrophilicity and Hydrophobicity 43415.4.3 Substrate Stiffness 43515.4.4 Surface Topography 43515.5 Biomimicked and Bioinspired Approaches 43615.5.1 Bone Tissue Regeneration 43915.5.2 Cartilage Tissue Regeneration 44015.5.3 Cardiac Tissue Regeneration 44115.6 Conclusion 442References 442

Ashutosh Tiwari is Secretary General, International Association of Advanced Materials; Chairman and Managing Director of Tekidag AB (Innotech); Associate Professor and Group Leader, Smart Materials and Biodevices at the world premier Biosensors and Bioelectronics Centre, IFM-Linköping University; Editor-in-Chief, Advanced Materials Letters; a materials chemist and docent in the Applied Physics with the specialization of Biosensors and Bioelectronics from Linköping University, Sweden. He has more than 100 peer-reviewed primary research publications in the field of materials science and nanotechnology and has edited/authored more than 35 books on advanced materials and technologyBora Garipcan teaches at Boðaziçi University, Turkey.Lokman Uzun is an Associate Professor at the Department of Chemistry, Biochemistry Division, Hacettepe University, Ankara, Turkey where he also received his PhD in 2008. He is the author of more than 75 articles in peer-review journals and is the Assistant Editor of Hacettepe’s Journal of Biology and Chemistry. He recently took up a fellowship with the Biosensors and Bioelectronics Centre, Linköping University, Sweden. His research interest is mainly in materials science, surface modification, affinity interaction, polymer science, especially molecularly imprinted polymers and their applications in biosensors, bioseparation, food safety, and the environmental sciences.

• Preface xv1 Extracellular Matrix Proteins for Stem Cell Fate 1Betül Çelebi-Saltik1.1 Human Stem Cells, Sources, and Niches 21.2 Role of Extrinsic and Intrinsic Factors 51.2.1 Shape 51.2.2 Topography Regulates Cell Fate 61.2.3 Stiffness and Stress 61.2.4 Integrins 71.2.5 Signaling via Integrins 91.3 Extracellular Matrix of the Mesenchyme: Human Bone Marrow 111.4 Biomimetic Peptides as Extracellular Matrix Proteins 13References 152 The Superficial Mechanical and Physical Properties of Matrix Microenvironment as Stem Cell Fate Regulator 23Mohsen Shahrousvand, Gity Mir Mohamad Sadeghi and Ali Salimi2.1 Introduction 242.2 Fabrication of the Microenvironments with Different Properties in Surfaces 252.3 Effects of Surface Topography on Stem Cell Behaviors 282.4 Role of Substrate Stiffness and Elasticity of Matrix on Cell Culture 312.5 Stem Cell Fate Induced by Matrix Stiffness and Its Mechanism 322.6 Competition/Compliance between Matrix Stiffness and Other Signals and Their Effect on Stem Cells Fate 332.7 Effects of Matrix Stiffness on Stem Cells in Two Dimensions versus Three Dimensions 342.8 Effects of External Mechanical Cues on Stem Cell Fate from Surface Interactions Perspective 342.9 Conclusions 35Acknowledgments 36References 363 Effects of Mechanotransduction on Stem Cell Behavior 43Bahar Bilgen and Sedat Odabas3.1 Introduction 433.2 The Concept of Mechanotransduction 453.3 The Mechanical Cues of Cell Differentiation and Tissue Formation on the Basis of Mechanotransduction 463.4 Mechanotransduction via External Forces 473.4.1 Mechanotransduction via Bioreactors 483.4.2 Mechanotransduction via Particle-based Systems 513.4.3 Mechanotransduction via Other External Forces 533.5 Mechanotransduction via Bioinspired Materials 543.6 Future Remarks and Conclusion 54Declaration of Interest 55References 554 Modulation of Stem Cells Behavior Through Bioactive Surfaces 65Eduardo D. Gomes, Rita C. Assunção-Silva, Nuno Sousax, Nuno A. Silva and António J. Salgado4.1 Lithography 664.2 Micro and Nanopatterning 704.3 Microfluidics 714.4 Electrospinning 714.5 Bottom-up/Top-down  Approaches 744.6 Substrates Chemical Modifications 754.6.1 Biomolecules Coatings 764.6.2 Peptide Grafting 774.7 Conclusion 78References 79Contents vii5 Influence of Controlled Micro- and Nanoengineered Environments on Stem Cell Fate 85Anna Lagunas, David Caballero and Josep Samitier5.1 Introduction to Engineered Environments for the Control of Stem Cell Differentiation 865.1.1 Stem Cells Niche In Vivo: A Highly Dynamic and Complex Environment 865.1.2 Mimicking the Stem Cells Niche In Vitro: Engineered Biomaterials 885.2 Mechanoregulation of Stem Cell Fate 895.2.1 From In Vivo to In Vitro: Influence of the Mechanical Environment on Stem Cell Fate 895.2.2 Regulation of Stem Cell Fate by Surface Roughness 905.2.3 Control of Stem Cell Differentiation by Micro- and Nanotopographic Surfaces 925.2.4 Physical Gradients for Regulating Stem Cell Fate 965.3 Controlled Surface Immobilization of Biochemical Stimuli for Stem Cell Differentiation 1005.3.1 Micro- and Nanopatterned Surfaces: Effect of Geometrical Constraint and Ligand Presentation at the Nanoscale 1005.3.2 Biochemical Gradients for Stem Cell Differentiation 1075.4 Three-dimensional Micro- and Nanoengineered Environments for Stem Cell Differentiation 1125.4.1 Three-dimensional Mechanoregulation of Stem Cell Fate 1135.4.2 Three-dimensional Biochemical Patterns for Stem Cell Differentiation 1195.5 Conclusions and Future Perspectives 122References 1226 Recent Advances in Nanostructured Polymeric Surface: Challenges and Frontiers in Stem Cells 141Ilaria Armentano, Samantha Mattioli, Francesco Morena, Chiara Argentati, Sabata Martino, Luigi Torre and Josè Maria Kenny6.1 Introduction 1426.2 Nanostructured Surface 1446.3 Stem Cell 1466.4 Stem Cell/Surface Interaction 1476.5 Microscopic Techniques Used in Estimating Stem Cell/Surface 1486.5.1 Fluorescence Microscopy 1486.5.2 Electron Microscopy 1496.5.3 Atomic Force Microscopy 1536.5.3.1 Instrument 1546.5.3.2 Cell Nanomechanical Motion 1566.5.3.3 Mechanical Properties 1566.6 Conclusions and Future Perspectives 158References 1587 Laser Surface Modification Techniques and Stem Cells  Applications 165Çağrı Kaan Akkan7.1 Introduction 1667.2 Fundamental Laser Optics for Surface Structuring 1667.2.1 Definitive Facts for Laser Surface Structuring 1677.2.1.1 Absorptivity and Reflectivity of the Laser Beam by the Material Surface 1677.2.1.2 Effect of the Incoming Laser Light Polarization 1687.2.1.3 Operation Mode of the Laser 1697.2.1.4 Beam Quality Factor 1707.2.1.5 Laser Pulse Energy/Power 1717.2.2 Ablation by Laser Pulses 1727.2.2.1 Focusing the Laser Beam 1727.2.2.2 Ablation Regime 1737.3 Methods for Laser Surface Structuring 1747.3.1 Physical Surface Modifications by Lasers 1747.3.1.1 Direct Structuring 1757.3.1.2 Beam Shaping Optics 1777.3.1.3 Direct Laser Interference Patterning 1807.3.2 Chemical Surface Modification by Lasers 1817.3.2.1 Pulsed Laser Deposition 1817.3.2.2 Laser Surface Alloying 1847.3.2.3 Laser Surface Oxidation and Nitriding 1867.4 Stem Cells and Laser-Modified Surfaces 1877.5 Conclusions 191References 1928 Plasma Polymer Deposition: A Versatile Tool for Stem Cell Research 197M. N. Macgregor-Ramiasa and K. Vasilev8.1 Introduction 1978.2 The Principle and Physics of Plasma Methods for Surface Modification 1998.2.1 Plasma Sputtering, Etching an Implantation 2008.2.2 Plasma Polymer Deposition 2018.3 Surface Properties Influencing Stem Cell Fate 2028.3.1 Plasma Methods for Tailored Surface Chemistry 2038.3.1.1 Oxygen-rich Surfaces 2048.3.1.2 Nitrogen-rich Surfaces 2088.3.1.3 Systematic Studies and Copolymers 2108.3.2 Plasma for Surface Topography 2118.3.3 Plasma for Surface Stiffness 2138.3.4 Plasma for Gradient Substrata 2158.3.5 Plasma and 3D Scaffolds 2188.4 New Trends and Outlook 2198.5 Conclusions 219References 2209 Three-dimensional Printing Approaches for the Treatment of Critical-sized Bone Defects 231Sara Salehi, Bilal A. Naved and Warren L. Grayson9.1 Background 2329.1.1 Treatment Approaches for Critical-sized Bone Defects 2329.1.2 History of the Application of 3D Printing to Medicine and Biology 2339.2 Overview of 3D Printing Technologies 2349.2.1 Laser-based Technologies 2359.2.1.1 Stereolithography 2359.2.1.2 Selective Laser Sintering 2369.2.1.3 Selective Laser Melting 2369.2.1.4 Electron Beam Melting 2379.2.1.5 Two-photon Polymerization 2379.2.2 Extrusion-based Technologies 2389.2.2.1 Fused Deposition Modeling 2389.2.2.2 Material Jetting 2389.2.3 Ink-based Technologies 2399.2.3.1 Inkjet 3D Printing 2399.2.3.2 Aerosol Jet Printing 2399.3 Surgical Guides and Models for Bone Reconstruction 2409.3.1 Laser-based Surgical Guides 2409.3.2 Extrusion-based Surgical Guides 2409.3.3 Ink-based Surgical Guides 2419.4 Three-dimensionally Printed Implants for Bone Substitution 2429.4.1 Laser-based Technologies for Metallic Bone Implants 2449.4.2 Extrusion-based Technologies for Bone Implants 2459.4.3 Ink-based Technologies for Bone Implants 2469.5 Scaffolds for Bone Regeneration 2469.5.1 Laser-based Printing for Regenerative Scaffolds 2479.5.2 Extrusion-based Printing for Regenerative Scaffolds 2479.5.3 Ink-based Printing for Regenerative Scaffolds 2499.5.4 Pre- and Postprocessing Techniques 2509.5.4.1 Preprocessing 2509.5.4.2 Postprocessing: Sintering 2569.5.4.3 Postprocessing: Functionalization 2569.6 Bioprinting 2579.7 Conclusion 262List of Abbreviation 263References 26410 Application of Bioreactor Concept and Modeling Techniques to Bone Regeneration and Augmentation Treatments 277Oscar A. Deccó and Jésica I. Zuchuat10.1 Bone Tissue Regeneration 27810.1.1 Proinflammatory Cytokines 27910.1.2 Transforming Growth Factor Beta 27910.1.3 Angiogenesis in Regeneration 28010.2 Actual Therapeutic Strategies and Concepts toObtain an Optimal Bone Quality and Quantity 28110.2.1 Guided Bone Regeneration Based on Cells 28210.2.1.1 Embryonic Stem Cells 28210.2.1.2 Adult Stem Cells 28210.2.1.3 Mesenchymal Stem Cells 28310.2.2 Guided Bone Regeneration Based on PRP and Growth Factors 28410.2.2.1 Bone Morphogenetic Proteins 28710.2.3 Guided Bone Regeneration Based on Barrier Membranes 28810.2.4 Guided Bone Regeneration Based on Scaffolds 29010.3 Bioreactors Employed for Tissue Engineering in Guided Bone Regeneration 29110.4 Bioreactor Concept in Guided Bone Regeneration and Tissue Engineering: In Vivo Application 29410.5 New Multidisciplinary Approaches Intended to Improve and Accelerate the Treatment of Injured and/or Diseased Bone 30310.5.1 Application of Bioreactor in Dentistry: Therapies for the Treatment of Maxillary Bone Defects 30410.5.2 Application of Bioreactor in Cases of Osteoporosis 30710.6 Computational Modeling: An Effective Tool to Predict Bone Ingrowth 310References 31111 Stem Cell-based Medicinal Products: Regulatory Perspectives 321DenizOzdil and Halil Murat Aydin11.1 Introduction 32111.2 Defining Stem Cell-based Medicinal Products 32311.3 Regional Regulatory Issues for Stem Cell Products 32611.4 Regulatory Systems for Stem Cell-based Technologies 32711.4.1 The US Regulatory System 32811.5 Stem Cell Technologies: The EuropeanRegulatory System 336References 34012 Substrates and Surfaces for Control of Pluripotent Stem Cell Fate and Function 341Akshaya Srinivasan, Yi-Chin Toh, Xian Jun Loh and Wei Seong Toh12.1 Introduction 34212.2 Pluripotent Stem Cells 34212.3 Substrates for Maintenance of Self-renewal and Pluripotency of PSCs 34412.3.1 Cellular Substrates 34412.3.2 Acellular Substrates 34512.3.2.1 Biological Matrices 34512.3.2.2 ECM Components 34812.3.2.3 Decellularized Matrices 35012.3.2.4 Cell Adhesion Molecules 35112.3.2.5 Synthetic Substrates 35212.4 Substrates for Promoting Differentiation of PSCs 35512.4.1 Cellular Substrates 35512.4.2 Acellular Substrates 35612.4.2.1 Biological Matrices 35612.4.2.2 ECM Components 35812.4.2.3 Decellularized Matrices 36212.4.2.4 Cell Adhesion Molecules 36312.4.2.5 Synthetic Substrates 36312.5 Conclusions 366Acknowledgments 367References 36713 Silk as a Natural Biopolymer for Tissue Engineering 379Ayşe Ak Can and Gamze Bölükbaşi Ateş13.1 Introduction 38013.2 SF as a Biomaterial 38313.2.1 Fibroin Hydrogels and Sponges 38413.2.2 Fibroin Films and Membranes 38613.2.3 Nonwoven and Woven Silk Scaffolds 38613.2.4 Silk Fibroin as a Bioactive Molecule Delivery 38613.3 Biomedical Applications of Silk-based Biomaterials 38713.3.1 Bone Tissue Engineering 38713.3.2 Cartilage Tissue Engineering 38913.3.3 Ligament and Tendon Tissue Engineering 39113.3.4 Cardiovascular Tissue Engineering 39113.3.5 Skin Tissue Engineering 39313.3.6 Other Applications of Silk Fibroin 39313.4 Conclusion and Future Directions 393References 39414 Applications of Biopolymer-based, Surface-modified Devices in Transplant Medicine and Tissue Engineering 399Ashim Malhotra, Gulnaz Javan and Shivani Soni14.1 Introduction to Cardiovascular Disease 40014.2 Need Assessment for Biopolymer-based Devices in Cardiovascular Therapeutics 40014.3 Emergence of Surface Modification Applications in Cardiovascular Sciences: A Historical Perspective 40114.4 Nitric Oxide Producing Biosurface Modification 40314.5 Surface Modification by Extracellular Matrix Protein Adherence 40414.6 The Role of Surface Modification in the Construction of Cardiac Prostheses 40514.7 Biopolymer-based Surface Modification of Materials Used in Bone Reconstruction 40614.8 The Use of Biopolymers in Nanotechnology 40914.8.1 Protein Nanoparticles 41014.8.1.1 Albumin-based Nanoparticles and Surface Modification 41114.8.1.2 Collagen-based Nanoparticles and Surface Modification 41214.8.1.3 Gelatin-based Nanoparticle Systems 41314.8.2 Polysaccharide-based Nanoparticle Systems 41314.8.2.1 The Use of Alginate for Surface Modifications 41314.8.2.2 The Use of Chitosan-based Nanoparticles and Chitosan-based Surface Modification 41414.8.2.3 The Use of Chitin-based Nanoparticles and Chitin-based Surface Modification 41614.8.2.4 The Use of Cellulose-based Nanoparticles and Cellulose-based Surface Modification 417References 41815 Stem Cell Behavior on Microenvironment Mimicked Surfaces  423M. Özgen Öztürk Öncel and Bora Garipcan15.1 Introduction 42415.2 Stem Cells 42515.2.1 Definition and Types 42515.2.1.1 Embryonic Stem Cells 42615.2.1.2 Adult Stem Cells 42615.2.1.3 Reprogramming and Induced Pluripotent Stem Cells 42715.2.2 Stem Cell Niche 42715.3 Stem Cells: Microenvironment Interactions 42815.3.1 Extracellular Matrix 42915.3.2 Signaling Factors 42915.3.3 Physicochemical Composition 43015.3.4 Mechanical Properties 43015.3.5 Cell–Cell Interactions 43115.4 Biomaterials as Stem Cell Microenvironments 43115.4.1 Surface Chemistry 43115.4.2 Surface Hydrophilicity and Hydrophobicity 43415.4.3 Substrate Stiffness 43515.4.4 Surface Topography 43515.5 Biomimicked and Bioinspired Approaches 43615.5.1 Bone Tissue Regeneration 43915.5.2 Cartilage Tissue Regeneration 44015.5.3 Cardiac Tissue Regeneration 44115.6 Conclusion 442References 442

Ashutosh Tiwari is Secretary General, International Association of Advanced Materials; Chairman and Managing Director of Tekidag AB (Innotech); Associate Professor and Group Leader, Smart Materials and Biodevices at the world premier Biosensors and Bioelectronics Centre, IFM-Linköping University; Editor-in-Chief, Advanced Materials Letters; a materials chemist and docent in the Applied Physics with the specialization of Biosensors and Bioelectronics from Linköping University, Sweden. He has more than 100 peer-reviewed primary research publications in the field of materials science and nanotechnology and has edited/authored more than 35 books on advanced materials and technologyBora Garipcan teaches at Boðaziçi University, Turkey.Lokman Uzun is an Associate Professor at the Department of Chemistry, Biochemistry Division, Hacettepe University, Ankara, Turkey where he also received his PhD in 2008. He is the author of more than 75 articles in peer-review journals and is the Assistant Editor of Hacettepe’s Journal of Biology and Chemistry. He recently took up a fellowship with the Biosensors and Bioelectronics Centre, Linköping University, Sweden. His research interest is mainly in materials science, surface modification, affinity interaction, polymer science, especially molecularly imprinted polymers and their applications in biosensors, bioseparation, food safety, and the environmental sciences.

• Preface xv1 Extracellular Matrix Proteins for Stem Cell Fate 1Betül Çelebi-Saltik1.1 Human Stem Cells, Sources, and Niches 21.2 Role of Extrinsic and Intrinsic Factors 51.2.1 Shape 51.2.2 Topography Regulates Cell Fate 61.2.3 Stiffness and Stress 61.2.4 Integrins 71.2.5 Signaling via Integrins 91.3 Extracellular Matrix of the Mesenchyme: Human Bone Marrow 111.4 Biomimetic Peptides as Extracellular Matrix Proteins 13References 152 The Superficial Mechanical and Physical Properties of Matrix Microenvironment as Stem Cell Fate Regulator 23Mohsen Shahrousvand, Gity Mir Mohamad Sadeghi and Ali Salimi2.1 Introduction 242.2 Fabrication of the Microenvironments with Different Properties in Surfaces 252.3 Effects of Surface Topography on Stem Cell Behaviors 282.4 Role of Substrate Stiffness and Elasticity of Matrix on Cell Culture 312.5 Stem Cell Fate Induced by Matrix Stiffness and Its Mechanism 322.6 Competition/Compliance between Matrix Stiffness and Other Signals and Their Effect on Stem Cells Fate 332.7 Effects of Matrix Stiffness on Stem Cells in Two Dimensions versus Three Dimensions 342.8 Effects of External Mechanical Cues on Stem Cell Fate from Surface Interactions Perspective 342.9 Conclusions 35Acknowledgments 36References 363 Effects of Mechanotransduction on Stem Cell Behavior 43Bahar Bilgen and Sedat Odabas3.1 Introduction 433.2 The Concept of Mechanotransduction 453.3 The Mechanical Cues of Cell Differentiation and Tissue Formation on the Basis of Mechanotransduction 463.4 Mechanotransduction via External Forces 473.4.1 Mechanotransduction via Bioreactors 483.4.2 Mechanotransduction via Particle-based Systems 513.4.3 Mechanotransduction via Other External Forces 533.5 Mechanotransduction via Bioinspired Materials 543.6 Future Remarks and Conclusion 54Declaration of Interest 55References 554 Modulation of Stem Cells Behavior Through Bioactive Surfaces 65Eduardo D. Gomes, Rita C. Assunção-Silva, Nuno Sousax, Nuno A. Silva and António J. Salgado4.1 Lithography 664.2 Micro and Nanopatterning 704.3 Microfluidics 714.4 Electrospinning 714.5 Bottom-up/Top-down  Approaches 744.6 Substrates Chemical Modifications 754.6.1 Biomolecules Coatings 764.6.2 Peptide Grafting 774.7 Conclusion 78References 79Contents vii5 Influence of Controlled Micro- and Nanoengineered Environments on Stem Cell Fate 85Anna Lagunas, David Caballero and Josep Samitier5.1 Introduction to Engineered Environments for the Control of Stem Cell Differentiation 865.1.1 Stem Cells Niche In Vivo: A Highly Dynamic and Complex Environment 865.1.2 Mimicking the Stem Cells Niche In Vitro: Engineered Biomaterials 885.2 Mechanoregulation of Stem Cell Fate 895.2.1 From In Vivo to In Vitro: Influence of the Mechanical Environment on Stem Cell Fate 895.2.2 Regulation of Stem Cell Fate by Surface Roughness 905.2.3 Control of Stem Cell Differentiation by Micro- and Nanotopographic Surfaces 925.2.4 Physical Gradients for Regulating Stem Cell Fate 965.3 Controlled Surface Immobilization of Biochemical Stimuli for Stem Cell Differentiation 1005.3.1 Micro- and Nanopatterned Surfaces: Effect of Geometrical Constraint and Ligand Presentation at the Nanoscale 1005.3.2 Biochemical Gradients for Stem Cell Differentiation 1075.4 Three-dimensional Micro- and Nanoengineered Environments for Stem Cell Differentiation 1125.4.1 Three-dimensional Mechanoregulation of Stem Cell Fate 1135.4.2 Three-dimensional Biochemical Patterns for Stem Cell Differentiation 1195.5 Conclusions and Future Perspectives 122References 1226 Recent Advances in Nanostructured Polymeric Surface: Challenges and Frontiers in Stem Cells 141Ilaria Armentano, Samantha Mattioli, Francesco Morena, Chiara Argentati, Sabata Martino, Luigi Torre and Josè Maria Kenny6.1 Introduction 1426.2 Nanostructured Surface 1446.3 Stem Cell 1466.4 Stem Cell/Surface Interaction 1476.5 Microscopic Techniques Used in Estimating Stem Cell/Surface 1486.5.1 Fluorescence Microscopy 1486.5.2 Electron Microscopy 1496.5.3 Atomic Force Microscopy 1536.5.3.1 Instrument 1546.5.3.2 Cell Nanomechanical Motion 1566.5.3.3 Mechanical Properties 1566.6 Conclusions and Future Perspectives 158References 1587 Laser Surface Modification Techniques and Stem Cells  Applications 165Çağrı Kaan Akkan7.1 Introduction 1667.2 Fundamental Laser Optics for Surface Structuring 1667.2.1 Definitive Facts for Laser Surface Structuring 1677.2.1.1 Absorptivity and Reflectivity of the Laser Beam by the Material Surface 1677.2.1.2 Effect of the Incoming Laser Light Polarization 1687.2.1.3 Operation Mode of the Laser 1697.2.1.4 Beam Quality Factor 1707.2.1.5 Laser Pulse Energy/Power 1717.2.2 Ablation by Laser Pulses 1727.2.2.1 Focusing the Laser Beam 1727.2.2.2 Ablation Regime 1737.3 Methods for Laser Surface Structuring 1747.3.1 Physical Surface Modifications by Lasers 1747.3.1.1 Direct Structuring 1757.3.1.2 Beam Shaping Optics 1777.3.1.3 Direct Laser Interference Patterning 1807.3.2 Chemical Surface Modification by Lasers 1817.3.2.1 Pulsed Laser Deposition 1817.3.2.2 Laser Surface Alloying 1847.3.2.3 Laser Surface Oxidation and Nitriding 1867.4 Stem Cells and Laser-Modified Surfaces 1877.5 Conclusions 191References 1928 Plasma Polymer Deposition: A Versatile Tool for Stem Cell Research 197M. N. Macgregor-Ramiasa and K. Vasilev8.1 Introduction 1978.2 The Principle and Physics of Plasma Methods for Surface Modification 1998.2.1 Plasma Sputtering, Etching an Implantation 2008.2.2 Plasma Polymer Deposition 2018.3 Surface Properties Influencing Stem Cell Fate 2028.3.1 Plasma Methods for Tailored Surface Chemistry 2038.3.1.1 Oxygen-rich Surfaces 2048.3.1.2 Nitrogen-rich Surfaces 2088.3.1.3 Systematic Studies and Copolymers 2108.3.2 Plasma for Surface Topography 2118.3.3 Plasma for Surface Stiffness 2138.3.4 Plasma for Gradient Substrata 2158.3.5 Plasma and 3D Scaffolds 2188.4 New Trends and Outlook 2198.5 Conclusions 219References 2209 Three-dimensional Printing Approaches for the Treatment of Critical-sized Bone Defects 231Sara Salehi, Bilal A. Naved and Warren L. Grayson9.1 Background 2329.1.1 Treatment Approaches for Critical-sized Bone Defects 2329.1.2 History of the Application of 3D Printing to Medicine and Biology 2339.2 Overview of 3D Printing Technologies 2349.2.1 Laser-based Technologies 2359.2.1.1 Stereolithography 2359.2.1.2 Selective Laser Sintering 2369.2.1.3 Selective Laser Melting 2369.2.1.4 Electron Beam Melting 2379.2.1.5 Two-photon Polymerization 2379.2.2 Extrusion-based Technologies 2389.2.2.1 Fused Deposition Modeling 2389.2.2.2 Material Jetting 2389.2.3 Ink-based Technologies 2399.2.3.1 Inkjet 3D Printing 2399.2.3.2 Aerosol Jet Printing 2399.3 Surgical Guides and Models for Bone Reconstruction 2409.3.1 Laser-based Surgical Guides 2409.3.2 Extrusion-based Surgical Guides 2409.3.3 Ink-based Surgical Guides 2419.4 Three-dimensionally Printed Implants for Bone Substitution 2429.4.1 Laser-based Technologies for Metallic Bone Implants 2449.4.2 Extrusion-based Technologies for Bone Implants 2459.4.3 Ink-based Technologies for Bone Implants 2469.5 Scaffolds for Bone Regeneration 2469.5.1 Laser-based Printing for Regenerative Scaffolds 2479.5.2 Extrusion-based Printing for Regenerative Scaffolds 2479.5.3 Ink-based Printing for Regenerative Scaffolds 2499.5.4 Pre- and Postprocessing Techniques 2509.5.4.1 Preprocessing 2509.5.4.2 Postprocessing: Sintering 2569.5.4.3 Postprocessing: Functionalization 2569.6 Bioprinting 2579.7 Conclusion 262List of Abbreviation 263References 26410 Application of Bioreactor Concept and Modeling Techniques to Bone Regeneration and Augmentation Treatments 277Oscar A. Deccó and Jésica I. Zuchuat10.1 Bone Tissue Regeneration 27810.1.1 Proinflammatory Cytokines 27910.1.2 Transforming Growth Factor Beta 27910.1.3 Angiogenesis in Regeneration 28010.2 Actual Therapeutic Strategies and Concepts toObtain an Optimal Bone Quality and Quantity 28110.2.1 Guided Bone Regeneration Based on Cells 28210.2.1.1 Embryonic Stem Cells 28210.2.1.2 Adult Stem Cells 28210.2.1.3 Mesenchymal Stem Cells 28310.2.2 Guided Bone Regeneration Based on PRP and Growth Factors 28410.2.2.1 Bone Morphogenetic Proteins 28710.2.3 Guided Bone Regeneration Based on Barrier Membranes 28810.2.4 Guided Bone Regeneration Based on Scaffolds 29010.3 Bioreactors Employed for Tissue Engineering in Guided Bone Regeneration 29110.4 Bioreactor Concept in Guided Bone Regeneration and Tissue Engineering: In Vivo Application 29410.5 New Multidisciplinary Approaches Intended to Improve and Accelerate the Treatment of Injured and/or Diseased Bone 30310.5.1 Application of Bioreactor in Dentistry: Therapies for the Treatment of Maxillary Bone Defects 30410.5.2 Application of Bioreactor in Cases of Osteoporosis 30710.6 Computational Modeling: An Effective Tool to Predict Bone Ingrowth 310References 31111 Stem Cell-based Medicinal Products: Regulatory Perspectives 321DenizOzdil and Halil Murat Aydin11.1 Introduction 32111.2 Defining Stem Cell-based Medicinal Products 32311.3 Regional Regulatory Issues for Stem Cell Products 32611.4 Regulatory Systems for Stem Cell-based Technologies 32711.4.1 The US Regulatory System 32811.5 Stem Cell Technologies: The EuropeanRegulatory System 336References 34012 Substrates and Surfaces for Control of Pluripotent Stem Cell Fate and Function 341Akshaya Srinivasan, Yi-Chin Toh, Xian Jun Loh and Wei Seong Toh12.1 Introduction 34212.2 Pluripotent Stem Cells 34212.3 Substrates for Maintenance of Self-renewal and Pluripotency of PSCs 34412.3.1 Cellular Substrates 34412.3.2 Acellular Substrates 34512.3.2.1 Biological Matrices 34512.3.2.2 ECM Components 34812.3.2.3 Decellularized Matrices 35012.3.2.4 Cell Adhesion Molecules 35112.3.2.5 Synthetic Substrates 35212.4 Substrates for Promoting Differentiation of PSCs 35512.4.1 Cellular Substrates 35512.4.2 Acellular Substrates 35612.4.2.1 Biological Matrices 35612.4.2.2 ECM Components 35812.4.2.3 Decellularized Matrices 36212.4.2.4 Cell Adhesion Molecules 36312.4.2.5 Synthetic Substrates 36312.5 Conclusions 366Acknowledgments 367References 36713 Silk as a Natural Biopolymer for Tissue Engineering 379Ayşe Ak Can and Gamze Bölükbaşi Ateş13.1 Introduction 38013.2 SF as a Biomaterial 38313.2.1 Fibroin Hydrogels and Sponges 38413.2.2 Fibroin Films and Membranes 38613.2.3 Nonwoven and Woven Silk Scaffolds 38613.2.4 Silk Fibroin as a Bioactive Molecule Delivery 38613.3 Biomedical Applications of Silk-based Biomaterials 38713.3.1 Bone Tissue Engineering 38713.3.2 Cartilage Tissue Engineering 38913.3.3 Ligament and Tendon Tissue Engineering 39113.3.4 Cardiovascular Tissue Engineering 39113.3.5 Skin Tissue Engineering 39313.3.6 Other Applications of Silk Fibroin 39313.4 Conclusion and Future Directions 393References 39414 Applications of Biopolymer-based, Surface-modified Devices in Transplant Medicine and Tissue Engineering 399Ashim Malhotra, Gulnaz Javan and Shivani Soni14.1 Introduction to Cardiovascular Disease 40014.2 Need Assessment for Biopolymer-based Devices in Cardiovascular Therapeutics 40014.3 Emergence of Surface Modification Applications in Cardiovascular Sciences: A Historical Perspective 40114.4 Nitric Oxide Producing Biosurface Modification 40314.5 Surface Modification by Extracellular Matrix Protein Adherence 40414.6 The Role of Surface Modification in the Construction of Cardiac Prostheses 40514.7 Biopolymer-based Surface Modification of Materials Used in Bone Reconstruction 40614.8 The Use of Biopolymers in Nanotechnology 40914.8.1 Protein Nanoparticles 41014.8.1.1 Albumin-based Nanoparticles and Surface Modification 41114.8.1.2 Collagen-based Nanoparticles and Surface Modification 41214.8.1.3 Gelatin-based Nanoparticle Systems 41314.8.2 Polysaccharide-based Nanoparticle Systems 41314.8.2.1 The Use of Alginate for Surface Modifications 41314.8.2.2 The Use of Chitosan-based Nanoparticles and Chitosan-based Surface Modification 41414.8.2.3 The Use of Chitin-based Nanoparticles and Chitin-based Surface Modification 41614.8.2.4 The Use of Cellulose-based Nanoparticles and Cellulose-based Surface Modification 417References 41815 Stem Cell Behavior on Microenvironment Mimicked Surfaces  423M. Özgen Öztürk Öncel and Bora Garipcan15.1 Introduction 42415.2 Stem Cells 42515.2.1 Definition and Types 42515.2.1.1 Embryonic Stem Cells 42615.2.1.2 Adult Stem Cells 42615.2.1.3 Reprogramming and Induced Pluripotent Stem Cells 42715.2.2 Stem Cell Niche 42715.3 Stem Cells: Microenvironment Interactions 42815.3.1 Extracellular Matrix 42915.3.2 Signaling Factors 42915.3.3 Physicochemical Composition 43015.3.4 Mechanical Properties 43015.3.5 Cell–Cell Interactions 43115.4 Biomaterials as Stem Cell Microenvironments 43115.4.1 Surface Chemistry 43115.4.2 Surface Hydrophilicity and Hydrophobicity 43415.4.3 Substrate Stiffness 43515.4.4 Surface Topography 43515.5 Biomimicked and Bioinspired Approaches 43615.5.1 Bone Tissue Regeneration 43915.5.2 Cartilage Tissue Regeneration 44015.5.3 Cardiac Tissue Regeneration 44115.6 Conclusion 442References 442