Advanced Surfaces for Stem Cell Research

The book outlines first the importance of Extra Cellular Matrix (ECM), which is a natural surface for most of cells. In the following chapters the influence of biological, chemical, mechanical, and physical properties of surfaces in micro and nano-scale on stem cell behavior are discussed including the mechanotransduction. Biomimetic and bioinspired approaches are highlighted for developing microenvironment of several tissues, and surface engineering applications are discussed in tissue engineering, regenerative medicine and different type of biomaterials in various chapters of the book.

This book brings together innovative methodologies and strategies adopted in the research and development of Advanced Surfaces in Stem Cell Research. Well-known worldwide researchers deliberate subjects including:

• Extracellular matrix proteins for stem cell fate
• The superficial mechanical and physical properties of matrix microenvironment as stem cell fate regulator
• Effects of mechanotransduction on stem cell behavior
• Modulation of stem cells behavior through bioactive surfaces
• Influence of controlled micro and nanoengineered surfaces on stem cell fate
• Nanostructured polymeric surfaces for stem cells
• Laser surface modification techniques and stem cells applications
• Plasma polymer deposition: a versatile tool for stem cell research
• Application of bioreactor concept and modeling techniques in bone regeneration and augmentation treatments
• Substrates and surfaces for control of pluripotent stem cell fate and function
• Application of biopolymer-based, surface modified devices in transplant medicine and tissue engineering
• Silk as a natural biopolymer for tissue engineering

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 technology

Bora 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 xv

1 Extracellular Matrix Proteins for Stem Cell Fate 1
Betül Çelebi-Saltik

1.1 Human Stem Cells, Sources, and Niches 2

1.2 Role of Extrinsic and Intrinsic Factors 5

1.2.1 Shape 5

1.2.2 Topography Regulates Cell Fate 6

1.2.3 Stiffness and Stress 6

1.2.4 Integrins 7

1.2.5 Signaling via Integrins 9

1.3 Extracellular Matrix of the Mesenchyme: Human Bone Marrow 11

1.4 Biomimetic Peptides as Extracellular Matrix Proteins 13

References 15

2 The Superficial Mechanical and Physical Properties of Matrix Microenvironment as Stem Cell Fate Regulator 23
Mohsen Shahrousvand, Gity Mir Mohamad Sadeghi and Ali Salimi

2.1 Introduction 24

2.2 Fabrication of the Microenvironments with Different Properties in Surfaces 25

2.3 Effects of Surface Topography on Stem Cell Behaviors 28

2.4 Role of Substrate Stiffness and Elasticity of Matrix on Cell Culture 31

2.5 Stem Cell Fate Induced by Matrix Stiffness and Its Mechanism 32

2.6 Competition/Compliance between Matrix Stiffness and Other Signals and Their Effect on Stem Cells Fate 33

2.7 Effects of Matrix Stiffness on Stem Cells in Two Dimensions versus Three Dimensions 34

2.8 Effects of External Mechanical Cues on Stem Cell Fate from Surface Interactions Perspective 34

2.9 Conclusions 35

Acknowledgments 36

References 36

3 Effects of Mechanotransduction on Stem Cell Behavior 43
Bahar Bilgen and Sedat Odabas

3.1 Introduction 43

3.2 The Concept of Mechanotransduction 45

3.3 The Mechanical Cues of Cell Differentiation and Tissue Formation on the Basis of Mechanotransduction 46

3.4 Mechanotransduction via External Forces 47

3.4.1 Mechanotransduction via Bioreactors 48

3.4.2 Mechanotransduction via Particle-based Systems 51

3.4.3 Mechanotransduction via Other External Forces 53

3.5 Mechanotransduction via Bioinspired Materials 54

3.6 Future Remarks and Conclusion 54

Declaration of Interest 55

References 55

4 Modulation of Stem Cells Behavior Through Bioactive Surfaces 65
Eduardo D. Gomes, Rita C. Assunção-Silva, Nuno Sousax, Nuno A. Silva and António J. Salgado

4.1 Lithography 66

4.2 Micro and Nanopatterning 70

4.3 Microfluidics 71

4.4 Electrospinning 71

4.5 Bottom-up/Top-down  Approaches 74

4.6 Substrates Chemical Modifications 75

4.6.1 Biomolecules Coatings 76

4.6.2 Peptide Grafting 77

4.7 Conclusion 78

References 79

Contents vii

5 Influence of Controlled Micro- and Nanoengineered Environments on Stem Cell Fate 85
Anna Lagunas, David Caballero and Josep Samitier

5.1 Introduction to Engineered Environments for the Control of Stem Cell Differentiation 86

5.1.1 Stem Cells Niche In Vivo: A Highly Dynamic and Complex Environment 86

5.1.2 Mimicking the Stem Cells Niche In Vitro: Engineered Biomaterials 88

5.2 Mechanoregulation of Stem Cell Fate 89

5.2.1 From In Vivo to In Vitro: Influence of the Mechanical Environment on Stem Cell Fate 89

5.2.2 Regulation of Stem Cell Fate by Surface Roughness 90

5.2.3 Control of Stem Cell Differentiation by Micro- and Nanotopographic Surfaces 92

5.2.4 Physical Gradients for Regulating Stem Cell Fate 96

5.3 Controlled Surface Immobilization of Biochemical Stimuli for Stem Cell Differentiation 100

5.3.1 Micro- and Nanopatterned Surfaces: Effect of Geometrical Constraint and Ligand Presentation at the Nanoscale 100

5.3.2 Biochemical Gradients for Stem Cell Differentiation 107

5.4 Three-dimensional Micro- and Nanoengineered Environments for Stem Cell Differentiation 112

5.4.1 Three-dimensional Mechanoregulation of Stem Cell Fate 113

5.4.2 Three-dimensional Biochemical Patterns for Stem Cell Differentiation 119

5.5 Conclusions and Future Perspectives 122

References 122

6 Recent Advances in Nanostructured Polymeric Surface: Challenges and Frontiers in Stem Cells 141
Ilaria Armentano, Samantha Mattioli, Francesco Morena, Chiara Argentati, Sabata Martino, Luigi Torre and Josè Maria Kenny

6.1 Introduction 142

6.2 Nanostructured Surface 144

6.3 Stem Cell 146

6.4 Stem Cell/Surface Interaction 147

6.5 Microscopic Techniques Used in Estimating Stem Cell/Surface 148

6.5.1 Fluorescence Microscopy 148

6.5.2 Electron Microscopy 149

6.5.3 Atomic Force Microscopy 153

6.5.3.1 Instrument 154

6.5.3.2 Cell Nanomechanical Motion 156

6.5.3.3 Mechanical Properties 156

6.6 Conclusions and Future Perspectives 158

References 158

7 Laser Surface Modification Techniques and Stem Cells  Applications 165
Çağrı Kaan Akkan

7.1 Introduction 166

7.2 Fundamental Laser Optics for Surface Structuring 166

7.2.1 Definitive Facts for Laser Surface Structuring 167

7.2.1.1 Absorptivity and Reflectivity of the Laser Beam by the Material Surface 167

7.2.1.2 Effect of the Incoming Laser Light Polarization 168

7.2.1.3 Operation Mode of the Laser 169

7.2.1.4 Beam Quality Factor 170

7.2.1.5 Laser Pulse Energy/Power 171

7.2.2 Ablation by Laser Pulses 172

7.2.2.1 Focusing the Laser Beam 172

7.2.2.2 Ablation Regime 173

7.3 Methods for Laser Surface Structuring 174

7.3.1 Physical Surface Modifications by Lasers 174

7.3.1.1 Direct Structuring 175

7.3.1.2 Beam Shaping Optics 177

7.3.1.3 Direct Laser Interference Patterning 180

7.3.2 Chemical Surface Modification by Lasers 181

7.3.2.1 Pulsed Laser Deposition 181

7.3.2.2 Laser Surface Alloying 184

7.3.2.3 Laser Surface Oxidation and Nitriding 186

7.4 Stem Cells and Laser-Modified Surfaces 187

7.5 Conclusions 191

References 192

8 Plasma Polymer Deposition: A Versatile Tool for Stem Cell Research 197
M. N. Macgregor-Ramiasa and K. Vasilev

8.1 Introduction 197

8.2 The Principle and Physics of Plasma Methods for Surface Modification 199

8.2.1 Plasma Sputtering, Etching an Implantation 200

8.2.2 Plasma Polymer Deposition 201

8.3 Surface Properties Influencing Stem Cell Fate 202

8.3.1 Plasma Methods for Tailored Surface Chemistry 203

8.3.1.1 Oxygen-rich Surfaces 204

8.3.1.2 Nitrogen-rich Surfaces 208

8.3.1.3 Systematic Studies and Copolymers 210

8.3.2 Plasma for Surface Topography 211

8.3.3 Plasma for Surface Stiffness 213

8.3.4 Plasma for Gradient Substrata 215

8.3.5 Plasma and 3D Scaffolds 218

8.4 New Trends and Outlook 219

8.5 Conclusions 219

References 220

9 Three-dimensional Printing Approaches for the Treatment of Critical-sized Bone Defects 231
Sara Salehi, Bilal A. Naved and Warren L. Grayson

9.1 Background 232

9.1.1 Treatment Approaches for Critical-sized Bone Defects 232

9.1.2 History of the Application of 3D Printing to Medicine and Biology 233

9.2 Overview of 3D Printing Technologies 234

9.2.1 Laser-based Technologies 235

9.2.1.1 Stereolithography 235

9.2.1.2 Selective Laser Sintering 236

9.2.1.3 Selective Laser Melting 236

9.2.1.4 Electron Beam Melting 237

9.2.1.5 Two-photon Polymerization 237

9.2.2 Extrusion-based Technologies 238

9.2.2.1 Fused Deposition Modeling 238

9.2.2.2 Material Jetting 238

9.2.3 Ink-based Technologies 239

9.2.3.1 Inkjet 3D Printing 239

9.2.3.2 Aerosol Jet Printing 239

9.3 Surgical Guides and Models for Bone Reconstruction 240

9.3.1 Laser-based Surgical Guides 240

9.3.2 Extrusion-based Surgical Guides 240

9.3.3 Ink-based Surgical Guides 241

9.4 Three-dimensionally Printed Implants for Bone Substitution 242

9.4.1 Laser-based Technologies for Metallic Bone Implants 244

9.4.2 Extrusion-based Technologies for Bone Implants 245

9.4.3 Ink-based Technologies for Bone Implants 246

9.5 Scaffolds for Bone Regeneration 246

9.5.1 Laser-based Printing for Regenerative Scaffolds 247

9.5.2 Extrusion-based Printing for Regenerative Scaffolds 247

9.5.3 Ink-based Printing for Regenerative Scaffolds 249

9.5.4 Pre- and Postprocessing Techniques 250

9.5.4.1 Preprocessing 250

9.5.4.2 Postprocessing: Sintering 256

9.5.4.3 Postprocessing: Functionalization 256

9.6 Bioprinting 257

9.7 Conclusion 262

List of Abbreviation 263

References 264

10 Application of Bioreactor Concept and Modeling Techniques to Bone Regeneration and Augmentation Treatments 277
Oscar A. Deccó and Jésica I. Zuchuat

10.1 Bone Tissue Regeneration 278

10.1.1 Proinflammatory Cytokines 279

10.1.2 Transforming Growth Factor Beta 279

10.1.3 Angiogenesis in Regeneration 280

10.2 Actual Therapeutic Strategies and Concepts to

Obtain an Optimal Bone Quality and Quantity 281

10.2.1 Guided Bone Regeneration Based on Cells 282

10.2.1.1 Embryonic Stem Cells 282

10.2.1.2 Adult Stem Cells 282

10.2.1.3 Mesenchymal Stem Cells 283

10.2.2 Guided Bone Regeneration Based on PRP and Growth Factors 284

10.2.2.1 Bone Morphogenetic Proteins 287

10.2.3 Guided Bone Regeneration Based on Barrier Membranes 288

10.2.4 Guided Bone Regeneration Based on Scaffolds 290

10.3 Bioreactors Employed for Tissue Engineering in Guided Bone Regeneration 291

10.4 Bioreactor Concept in Guided Bone Regeneration and Tissue Engineering: In Vivo Application 294

10.5 New Multidisciplinary Approaches Intended to Improve and Accelerate the Treatment of Injured and/or Diseased Bone 303

10.5.1 Application of Bioreactor in Dentistry: Therapies for the Treatment of Maxillary Bone Defects 304

10.5.2 Application of Bioreactor in Cases of Osteoporosis 307

10.6 Computational Modeling: An Effective Tool to Predict Bone Ingrowth 310

References 311

11 Stem Cell-based Medicinal Products: Regulatory Perspectives 321
DenizOzdil and Halil Murat Aydin

11.1 Introduction 321

11.2 Defining Stem Cell-based Medicinal Products 323

11.3 Regional Regulatory Issues for Stem Cell Products 326

11.4 Regulatory Systems for Stem Cell-based Technologies 327

11.4.1 The US Regulatory System 328

11.5 Stem Cell Technologies: The European

Regulatory System 336

References 340

12 Substrates and Surfaces for Control of Pluripotent Stem Cell Fate and Function 341
Akshaya Srinivasan, Yi-Chin Toh, Xian Jun Loh and Wei Seong Toh

12.1 Introduction 342

12.2 Pluripotent Stem Cells 342

12.3 Substrates for Maintenance of Self-renewal and Pluripotency of PSCs 344

12.3.1 Cellular Substrates 344

12.3.2 Acellular Substrates 345

12.3.2.1 Biological Matrices 345

12.3.2.2 ECM Components 348

12.3.2.3 Decellularized Matrices 350

12.3.2.4 Cell Adhesion Molecules 351

12.3.2.5 Synthetic Substrates 352

12.4 Substrates for Promoting Differentiation of PSCs 355

12.4.1 Cellular Substrates 355

12.4.2 Acellular Substrates 356

12.4.2.1 Biological Matrices 356

12.4.2.2 ECM Components 358

12.4.2.3 Decellularized Matrices 362

12.4.2.4 Cell Adhesion Molecules 363

12.4.2.5 Synthetic Substrates 363

12.5 Conclusions 366

Acknowledgments 367

References 367

13 Silk as a Natural Biopolymer for Tissue Engineering 379
Ayşe Ak Can and Gamze Bölükbaşi Ateş

13.1 Introduction 380

13.2 SF as a Biomaterial 383

13.2.1 Fibroin Hydrogels and Sponges 384

13.2.2 Fibroin Films and Membranes 386

13.2.3 Nonwoven and Woven Silk Scaffolds 386

13.2.4 Silk Fibroin as a Bioactive Molecule Delivery 386

13.3 Biomedical Applications of Silk-based Biomaterials 387

13.3.1 Bone Tissue Engineering 387

13.3.2 Cartilage Tissue Engineering 389

13.3.3 Ligament and Tendon Tissue Engineering 391

13.3.4 Cardiovascular Tissue Engineering 391

13.3.5 Skin Tissue Engineering 393

13.3.6 Other Applications of Silk Fibroin 393

13.4 Conclusion and Future Directions 393

References 394

14 Applications of Biopolymer-based, Surface-modified Devices in Transplant Medicine and Tissue Engineering 399
Ashim Malhotra, Gulnaz Javan and Shivani Soni

14.1 Introduction to Cardiovascular Disease 400

14.2 Need Assessment for Biopolymer-based Devices in Cardiovascular Therapeutics 400

14.3 Emergence of Surface Modification Applications in Cardiovascular Sciences: A Historical Perspective 401

14.4 Nitric Oxide Producing Biosurface Modification 403

14.5 Surface Modification by Extracellular Matrix Protein Adherence 404

14.6 The Role of Surface Modification in the Construction of Cardiac Prostheses 405

14.7 Biopolymer-based Surface Modification of Materials Used in Bone Reconstruction 406

14.8 The Use of Biopolymers in Nanotechnology 409

14.8.1 Protein Nanoparticles 410

14.8.1.1 Albumin-based Nanoparticles and Surface Modification 411

14.8.1.2 Collagen-based Nanoparticles and Surface Modification 412

14.8.1.3 Gelatin-based Nanoparticle Systems 413

14.8.2 Polysaccharide-based Nanoparticle Systems 413

14.8.2.1 The Use of Alginate for Surface Modifications 413

14.8.2.2 The Use of Chitosan-based Nanoparticles and Chitosan-based Surface Modification 414

14.8.2.3 The Use of Chitin-based Nanoparticles and Chitin-based Surface Modification 416

14.8.2.4 The Use of Cellulose-based Nanoparticles and Cellulose-based Surface Modification 417

References 418

15 Stem Cell Behavior on Microenvironment Mimicked Surfaces  423
M. Özgen Öztürk Öncel and Bora Garipcan

15.1 Introduction 424

15.2 Stem Cells 425

15.2.1 Definition and Types 425

15.2.1.1 Embryonic Stem Cells 426

15.2.1.2 Adult Stem Cells 426

15.2.1.3 Reprogramming and Induced Pluripotent Stem Cells 427

15.2.2 Stem Cell Niche 427

15.3 Stem Cells: Microenvironment Interactions 428

15.3.1 Extracellular Matrix 429

15.3.2 Signaling Factors 429

15.3.3 Physicochemical Composition 430

15.3.4 Mechanical Properties 430

15.3.5 Cell–Cell Interactions 431

15.4 Biomaterials as Stem Cell Microenvironments 431

15.4.1 Surface Chemistry 431

15.4.2 Surface Hydrophilicity and Hydrophobicity 434

15.4.3 Substrate Stiffness 435

15.4.4 Surface Topography 435

15.5 Biomimicked and Bioinspired Approaches 436

15.5.1 Bone Tissue Regeneration 439

15.5.2 Cartilage Tissue Regeneration 440

15.5.3 Cardiac Tissue Regeneration 441

15.6 Conclusion 442

References 442

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