Biomimetic Approaches for Biomaterials Development

Overview

Biomimetics, in general terms, aims at understanding biological principles and applying them for the development of man-made tools and technologies. This approach is particularly important for the purposeful design of passive as well as functional biomaterials that mimic physicochemical, mechanical and biological properties of natural materials, making them suitable, for example, for biomedical devices or as scaffolds for tissue regeneration.

The book comprehensively covers ...

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Overview

Biomimetics, in general terms, aims at understanding biological principles and applying them for the development of man-made tools and technologies. This approach is particularly important for the purposeful design of passive as well as functional biomaterials that mimic physicochemical, mechanical and biological properties of natural materials, making them suitable, for example, for biomedical devices or as scaffolds for tissue regeneration.

The book comprehensively covers biomimetic approaches to the development of biomaterials, including: an overview of naturally occurring or nature inspired biomaterials; an in-depth treatment of the surface aspects pivotal for the functionality; synthesis and self-assembly methods to prepare devices to be used in mineralized tissues such as bone and teeth; and preparation of biomaterials for the controlled/
sustained release of bioactive agents. The last part reviews the applications of bioinspired materials and principles of design in regenerative medicine such as in-situ grown bone or cartilage as well as the biomimetic techniques for soft tissue engineering.

The comprehensive scope of this book makes it a must-have addition to the bookshelf of everyone in the fields of Materials Science/Engineering, Nanotechnologies / Nanosciences, Medical Sciences, Biochemistry, Polymer Chemistry, and Biomedical Engineering.

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Product Details

  • ISBN-13: 9783527329168
  • Publisher: Wiley
  • Publication date: 12/25/2012
  • Edition number: 1
  • Pages: 606
  • Product dimensions: 6.90 (w) x 9.70 (h) x 1.40 (d)

Meet the Author

João F. Mano (CEng, PhD, DSc) is an Associate Professor at the Polymer Engineering Department, University of Minho, Portugal, and principal investigator at the 3B's research group - Biomaterials, Biodegradables and Biomimetics. He is the former director of the Master program in Biomedical Engineering at the University of Minho. His current research interests include the development of new materials and concepts for biomedical applications, especially aimed at being used in tissue engineering and in drug delivery systems. In particular, he has been developing biomaterials and surfaces that can react to external stimuli, or biomimetic and nanotechnology approaches to be used in the biomedical area. J.F. Mano authored more than 330 papers in international journals and three patents. He belongs to the editorial boards of 5 well-established international journals. J.F. Mano awarded the Stimulus to Excellence by the Portuguese Minister for Science and Technology in 2005, the Materials Science and Technology Prize, attributed by the Federation of European Materials Societies in 2007 and the major BES innovation award in 2010.

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Table of Contents

Preface XVII

List of Contributors XXI

Part I Examples of Natural and Nature-Inspired Materials 1

1 Biomaterials from Marine-Origin Biopolymers 3
Tiago H. Silva, Ana R.C. Duarte, Joana Moreira-Silva, Jo˜ao F. Mano, and Rui L. Reis

1.1 Taking Inspiration from the Sea 3

1.2 Marine-Origin Biopolymers 6

1.2.1 Chitosan 6

1.2.2 Alginate 8

1.2.3 Carrageenan 9

1.2.4 Collagen 9

1.2.5 Hyaluronic Acid 10

1.2.6 Others 11

1.3 Marine-Based Tissue Engineering Approaches 12

1.3.1 Membranes 12

1.3.2 Hydrogels 13

1.3.3 Tridimensional Porous Structures 15

1.3.4 Particles 17

1.4 Conclusions 18

References 18

2 Hydrogels from Protein Engineering 25
Midori Greenwood-Goodwin and Sarah C. Heilshorn

2.1 Introduction 25

2.2 Principles of Protein Engineering 26

2.2.1 Protein Structure and Folding 26

2.2.2 Design of Protein-Engineered Hydrogels 28

2.2.3 Production of Protein-Engineered Hydrogels 30

2.3 Structural Diversity and Applications of Protein-Engineered Hydrogels 32

2.3.1 Self-Assembled Protein Hydrogels 32

2.3.2 Covalently Cross-Linked Protein Hydrogels 38

2.4 Development of Biomimetic Protein-Engineered Hydrogels for Tissue Engineering Applications 39

2.4.1 Mechanical Properties Mediate Cellular Response 40

2.4.2 Biodegradable Hydrogels for Cell Invasion 41

2.4.3 Diverse Biochemical Cues Regulate Complex Cell Behaviors 43

2.4.3.1 Cell–Extracellular Matrix Binding Domains 43

2.4.3.2 Nanoscale Patterning of Cell–Extracellular Matrix Binding Domains 44

2.4.3.3 Cell–Cell Binding Domains 45

2.4.3.4 Delivery of Soluble Cell Signaling Molecules 46

2.5 Conclusions and Future Perspective 48

References 49

3 Collagen-Based Biomaterials for Regenerative Medicine 55
Christophe Helary and Abhay Pandit

3.1 Introduction 55

3.2 Collagens In Vivo 56

3.2.1 Collagen Structure 56

3.2.2 Collagen Fibrillogenesis 56

3.2.3 Three-Dimensional Networks of Collagen in Connective Tissues 57

3.2.4 Interactions of Cells with Collagen 57

3.3 Collagen In Vitro 59

3.4 Collagen Hydrogels 59

3.4.1 Collagen I Hydrogels 59

3.4.1.1 Classical Hydrogels 59

3.4.1.2 Concentrated Collagen Hydrogels 61

3.4.1.3 Dense Collagen Hydrogels Obtained by Plastic Compression 61

3.4.1.4 Dense Collagen Matrices 61

3.4.2 Cross-Linked Collagen I Hydrogels 62

3.4.2.1 Chemical Cross-Linking 62

3.4.2.2 Enzymatic Cross-Linking 62

3.4.3 Collagen II Hydrogels 63

3.4.4 Aligned Hydrogels and Extruded Fibers 64

3.4.4.1 Aligned Hydrogels 64

3.4.4.2 Extruded Collagen Fibers 65

3.5 Collagen Sponges 65

3.6 Multichannel Collagen Scaffolds 66

3.6.1 Multichannel Collagen Conduits 66

3.6.2 Multi-Channeled Collagen–Calcium Phosphate Scaffolds 66

3.7 What Tissues Do Collagen Biomaterials Mimic? (see Table 3.1) 66

3.7.1 Skin 66

3.7.2 Nerves 68

3.7.3 Tendons 68

3.7.4 Bone 69

3.7.5 Intervertebral Disk 69

3.7.6 Cartilage 70

3.8 Concluding Remarks 70

Acknowledgments 71

References 71

4 Silk-Based Biomaterials 75
Sá?lvia Gomes, Isabel B. Leonor, Jo˜ao F. Mano, Rui L. Reis, and David L. Kaplan

4.1 Introduction 75

4.2 Silk Proteins 76

4.2.1 Bombyx mori Silk 76

4.2.2 Spider Silk 77

4.2.3 Recombinant Silk 79

4.3 Mechanical Properties 82

4.4 Biomedical Applications of Silk 84

4.5 Final Remarks 87

References 88

5 Elastin-like Macromolecules 93
Rui R. Costa, Laura Martá?n, Jo˜ao F. Mano, and José C. Rodrá?guez-Cabello

5.1 General Introduction 93

5.2 Materials Engineering – an Overview on Synthetic and Natural Biomaterials 94

5.3 Elastin as a Source of Inspiration for Nature-Inspired Polymers 94

5.3.1 Genetic Coding 94

5.3.2 Characteristics of Elastin 95

5.3.3 Elastin Disorders 97

5.3.4 Current Applications of Elastin as Biomaterials 97

5.3.4.1 Skin 97

5.3.4.2 Vascular Constructs 98

5.4 Nature-Inspired Biosynthetic Elastins 99

5.4.1 General Properties of Elastin-like Recombinamers 99

5.4.2 The Principle of Genetic Engineering – a Powerful Tool for Engineering Materials 100

5.4.3 From Genetic Construction to Molecules with Tailored Biofunctionality 102

5.4.4 Biocompatibility of ELRs 103

5.5 ELRs as Advanced Materials for Biomedical Applications 103

5.5.1 Tissue Engineering 104

5.5.2 Drug and Gene Delivery 106

5.5.3 Surface Engineering 108

5.6 Conclusions 110

Acknowledgements 110

References 111

6 Biomimetic Molecular Recognition Elements for Chemical Sensing 117
Justyn Jaworski

6.1 Introduction 117

6.1.1 Overview 117

6.1.2 Biological Chemoreception 118

6.1.3 Host–Guest Interactions 119

6.1.3.1 Lock and Key 119

6.1.3.2 Induced Fit 120

6.1.3.3 Preexisting Equilibrium Model 121

6.1.4 Biomimetic Surfaces for Molecular Recognition 121

6.2 Theory of Molecular Recognition 123

6.2.1 Foundation of Molecular Recognition 123

6.2.2 Noncovalent Interactions 123

6.2.3 Thermodynamics of the Molecular Recognition Event 125

6.2.4 Putting a Figure of Merit on Molecular Recognition 127

6.2.5 Multiple Interactions: Avidity and Cooperativity 128

6.3 Molecularly Imprinted Polymers 129

6.3.1 A Brief History of Molecular Imprinting 129

6.3.2 Strategies for the Formation of Molecularly Imprinted Polymers 129

6.3.3 Polymer Matrix Design 130

6.3.4 Cross-Linking and Polymerization Approaches 131

6.3.5 Template Extraction 132

6.3.6 Limitations and Areas for Improvement 133

6.4 Supramolecular Chemistry 134

6.4.1 Introduction 134

6.4.2 Macrocyclic Effect 134

6.4.3 Chelate Effect 135

6.4.4 Preorganization, Rational Design, and Modeling 135

6.4.5 Templating Effect 136

6.4.6 Effective Supramolecular Receptors for Biomimetic Sensing 137

6.4.6.1 Calixarenes 137

6.4.6.2 Metalloporphyrins 138

6.4.7 Recent Improvement 139

6.5 Biomolecular Materials 140

6.5.1 Introduction 140

6.5.2 Native Biomolecules 141

6.5.2.1 Polypeptides 141

6.5.2.2 Carbohydrates 142

6.5.2.3 Oligonucleotides 143

6.5.3 Engineered Biomolecules 144

6.5.3.1 In vitro Selection of RNA/DNA Aptamers 144

6.5.3.2 Evolutionary Screened Peptides 146

6.5.3.3 Computational and Rational Design of Biomimetic Receptors 150

6.6 Summary and Future of Biomimetic-Sensor-Coating Materials 151

References 152

Part II Surface Aspects 157

7 Biology Lessons for Engineering Surfaces for Controlling Cell–Material Adhesion 159
Ted T. Lee and Andrés J. Garcá?a

7.1 Introduction 159

7.2 The Extracellular Matrix 159

7.3 Protein Structure 160

7.4 Basics of Protein Adsorption 161

7.5 Kinetics of Protein Adsorption 162

7.6 Cell Communication 164

7.6.1 Intracellular Communication 164

7.6.2 Intercellular Communication 165

7.7 Cell Adhesion Background 166

7.8 Integrins and Adhesive Force Generation Overview 167

7.9 Adhesive Interactions in Cell, and Host Responses to Biomaterials 170

7.10 Model Systems for Controlling Integrin-Mediated Cell Adhesion 170

7.11 Self-Assembling Monolayers (SAMs) 171

7.12 Real-World Materials for Medical Applications 172

7.12.1 Polymer Brush Systems 172

7.12.2 Hydrogels 173

7.13 Bio-Inspired, Adhesive Materials: New Routes to Promote Tissue Repair and Regeneration 174

7.14 Dynamic Biomaterials 176

7.14.1 Nonspecific ‘‘On’’ Switches 176

7.14.1.1 Electrochemical Desorption 176

7.14.1.2 Oxidative Release 177

7.14.2 Photobased Desorption 178

7.14.3 Integrin Specific ‘‘On’’ Switching 178

7.14.3.1 Photoactivation 178

7.14.4 Adhesion ‘‘Off’’ Switching 179

7.14.4.1 Electrochemical Off Switching 179

7.14.5 Reversible Adhesion Switches 181

7.14.5.1 Reversible Photoactive Switching 181

7.14.5.2 Reversible Temperature-Based Switching 182

7.14.6 Conclusions and Future Prospects 184

References 185

8 Fibronectin Fibrillogenesis at the Cell–Material Interface 189
Marco Cantini, Patricia Rico, and Manuel Salmerón-Sánchez

8.1 Introduction 189

8.2 Cell-Driven Fibronectin Fibrillogenesis 189

8.2.1 Fibronectin Structure 190

8.2.2 Essential Domains for FN Assembly 192

8.2.3 FN Fibrillogenesis and Regulation of Matrix Assembly 194

8.3 Cell-Free Assembly of Fibronectin Fibrils 195

8.4 Material-Driven Fibronectin Fibrillogenesis 202

8.4.1 Physiological Organization of Fibronectin at the Material Interface 203

8.4.2 Biological Activity of the Material-Driven Fibronectin Fibrillogenesis 206

References 210

9 Nanoscale Control of Cell Behavior on Biointerfaces 213
E. Ada Cavalcanti-Adam and Dimitris Missirlis

9.1 Nanoscale Cues in Cell Environment 213

9.2 Biomimetics of Cell Environment Using Interfaces 216

9.2.1 Surface Patterning Techniques at the Nanoscale 216

9.2.1.1 Surface Patterning by Nonconventional Nanolithography 216

9.2.1.2 Block Copolymer Micelle Lithography 217

9.2.2 Variation of Surface Physical Parameters at the Nanoscale 219

9.2.2.1 Surface Nanotopography 220

9.2.2.2 Interligand Spacing 221

9.2.2.3 Ligand Density 222

9.2.2.4 Substrate Mechanical Properties 223

9.2.2.5 Dimensionality 223

9.2.3 Surface Functionalization for Controlled Presentation of ECM Molecules to Cells 224

9.2.3.1 Proteins, Protein Fragments, and Peptides 224

9.2.3.2 Linking Systems 226

9.2.3.3 Modulation of Substrate Background 227

9.3 Cell Responses to Nanostructured Materials 227

9.3.1 Cell Adhesion and Migration 228

9.3.2 Cell–Cell Interactions 230

9.3.3 Cell Membrane Receptor Signaling 231

9.3.4 Applications of Nanostructures in Stem Cell Biology 232

9.4 The Road Ahead 233

References 234

10 Surfaces with Extreme Wettability Ranges for Biomedical Applications 237
Wenlong Song, Natália M. Alves, and Jo˜ao F. Mano

10.1 Superhydrophobic Surfaces in Nature 237

10.2 Theory of Surface Wettability 239

10.2.1 Young’s Model 239

10.2.2 Wenzel’s Model 240

10.2.3 The Cassie–Baxter Model 240

10.2.4 Transition between the Cassie–Baxter and Wenzel Models 240

10.3 Fabrication of Extreme Water-Repellent Surfaces Inspired by Nature 241

10.3.1 Superhydrophobic Surfaces Inspired by the Lotus Leaf 241

10.3.2 Superhydrophobic Surfaces Inspired by the Legs of the Water Strider 243

10.3.3 Superhydrophobic Surfaces Inspired by the Anisotropic Superhydrophobic Surfaces in Nature 244

10.3.4 Other Superhydrophobic Surfaces 245

10.4 Applications of Surfaces with Extreme Wettability Ranges in the Biomedical Field 245

10.4.1 Cell Interactions with Surfaces with Extreme Wettability Ranges 246

10.4.2 Protein Interactions with Surfaces with Extreme Wettability Ranges 249

10.4.3 Blood Interactions with Surfaces with Extreme Wettability Ranges 251

10.4.4 High-Throughput Chips Based on Surfaces with Extreme Wettability Ranges 252

10.4.5 Substrates for Preparing Hydrogel and Polymeric Particles 254

10.5 Conclusions 254

References 255

11 Bio-Inspired Reversible Adhesives for Dry and Wet Conditions 259
Aránzazu del Campo and Juan Pedro Fernández-Blázquez

11.1 Introduction 259

11.2 Gecko-Like Dry Adhesives 260

11.2.1 Fibrils with 3D Contact Shapes 262

11.2.2 Tilted Structures 263

11.2.3 Hierarchical Structures 265

11.2.4 Responsive Adhesion Patterns 265

11.3 Bioinspired Adhesives for Wet Conditions 268

11.4 The Future of Bio-Inspired Reversible Adhesives 270

Acknowledgments 270

References 270

12 Lessons from Sea Organisms to Produce New Biomedical Adhesives 273
Elise Hennebert, Pierre Becker, and Patrick Flammang

12.1 Introduction 273

12.2 Composition of Natural Adhesives 274

12.2.1 Mussels 274

12.2.2 Tube Worms 278

12.2.3 Barnacles 279

12.2.4 Brown Algae 280

12.3 Recombinant Adhesive Proteins 281

12.3.1 Production 281

12.3.2 Applications 283

12.4 Production of Bio-Inspired Synthetic Adhesive Polymers 284

12.4.1 Adhesives Based on Synthetic Peptides 285

12.4.2 Adhesives Based on Polysaccharides 285

12.4.3 Adhesives Based on Other Polymers 286

12.5 Perspectives 288

Acknowledgments 288

References 288

Part III Hard and Mineralized Systems 293

13 Interfacial Forces and Interfaces in Hard Biomaterial Mechanics 295
Devendra K. Dubey and Vikas Tomar

13.1 Introduction 295

13.2 Hard Biological Materials 298

13.2.1 Role of Interfaces in Hard Biomaterial Mechanics 299

13.2.2 Modeling of TC–HAP and Generic Polymer–Ceramic-Type Nanocomposites at Fundamental Length Scales 301

13.2.2.1 Analytical Modeling 302

13.2.2.2 Atomistic Modeling 304

13.3 Bioengineering and Biomimetics 306

13.4 Summary 308

References 309

14 Nacre-Inspired Biomaterials 313
Gisela M. Luz and Jo˜ao F. Mano

14.1 Introduction 313

14.2 Structure of Nacre 316

14.3 Why Is Nacre So Strong? 318

14.4 Strategies to Produce Nacre-Inspired Biomaterials 320

14.4.1 Covalent Self-Assembly or Bottom-Up Approach 320

14.4.2 Electrophoretic Deposition 322

14.4.3 Layer-by-Layer and Spin-Coating Methodologies 323

14.4.4 Template Inhibition 325

14.4.5 Freeze-Casting 326

14.4.6 Other Methodologies 326

14.5 Conclusions 328

Acknowledgements 329

References 329

15 Surfaces Inducing Biomineralization 333
Natália M. Alves, Isabel B. Leonor, Helena S. Azevedo, Rui. L. Reis, and Jo˜ao. F. Mano

15.1 Mineralized Structures in Nature: the Example of Bone 333

15.2 Learning from Nature to the Research Laboratory 336

15.2.1 Bioactive Ceramics and Their Bone-Bonding Mechanism 337

15.2.2 Is a Functional Group Enough to Render Biomaterials Self-Mineralizable? 338

15.2.2.1 How the Surface Charge of Functional Group Can Be Correlated to Apatite Formation? 338

15.2.2.2 Designing a Properly Functionalized Surface 339

15.3 Smart Mineralizing Surfaces 343

15.4 In Situ Self-Assembly on Implant Surfaces to Direct Mineralization 345

15.5 Conclusions 348

Acknowledgments 348

References 348

16 Bioactive Nanocomposites Containing Silicate Phases for Bone Replacement and Regeneration 353
Melek Erol, Jasmin Hum, and Aldo R. Boccaccini

16.1 Introduction 353

16.2 Nanostructure and Nanofeatures of the Bone 354

16.2.1 The Structure of Bone as a Nanocomposite 354

16.2.2 Cell Behavior at the Nanoscale 356

16.3 Nanocomposites-Containing Silicate Nanophases 356

16.3.1 Nanoscale Bioactive Glasses 356

16.3.1.1 Synthetic Polymer/Nanoparticulate Bioactive Glass Composites 357

16.3.1.2 Natural Polymer/Bioactive Glass Nanocomposites 360

16.3.2 Nanoscaled Silica 363

16.3.2.1 Composites Containing Silica Nanoparticles 364

16.3.3 Nanoclays 365

16.3.3.1 Composites Containing Clay Nanoparticles 366

16.4 Final Considerations 372

References 375

Part IV Systems for the Delivery of Bioactive Agents 381

17 Biomimetic Nanostructured Apatitic Matrices for Drug Delivery 383
Norberto Roveri and Michele Iafisco

17.1 Introduction 383

17.2 Biomimetic Apatite Nanocrystals 384

17.2.1 Properties 384

17.2.2 Synthesis 386

17.3 Biomedical Applications of Biomimetic Nanostructured Apatites 390

17.4 Biomimetic Nanostructured Apatite as Drug Delivery System 394

17.4.1 Adsorption and Release of Drugs 397

17.5 Adsorption and Release of Proteins 402

17.5.1 Adsorption and Release of Bisphosphonates 406

17.6 Conclusions and Perspectives 409

Acknowledgments 411

References 411

18 Nanostructures and Nanostructured Networks for Smart Drug Delivery 417
Carmen Alvarez-Lorenzo, Ana M. Puga, and Angel Concheiro

18.1 Introduction 417

18.2 Stimuli-Sensitive Materials 419

18.2.1 pH 419

18.2.2 Glutathione 420

18.2.3 Molecule-Responsive and Imprinted Systems 420

18.2.4 Temperature 422

18.2.5 Light 423

18.2.6 Electrical Field 425

18.2.7 Magnetic Field 426

18.2.8 Ultrasounds 427

18.2.9 Autonomous Responsiveness 428

18.3 Stimuli-Responsive Nanostructures and Nanostructured Networks 428

18.3.1 Self-Assembled Polymers: Micelles and Polymersomes 429

18.3.2 Treelike Polymers: Dendrimers 433

18.3.3 Layer-by-Layer Assembly of Preformed Polymers 436

18.3.4 Polymeric Particles from Preformed Polymers 438

18.3.5 Polymeric Particles from Monomers 439

18.3.6 Chemically Cross-Linked Hydrogels 444

18.3.7 Grafting onto Medical Devices 447

18.4 Concluding Remarks 449

Acknowledgments 449

References 450

19 Progress in Dendrimer-Based Nanocarriers 459
Joaquim M. Oliveira, Jo˜ao F. Mano, and Rui L. Reis

19.1 Fundamentals 459

19.2 Applications of Dendrimer-Based Polymers 460

19.2.1 Biomimetic/Bioinspired Materials 460

19.2.2 Drug Delivery Systems 461

19.2.3 Gene Delivery Systems 463

19.2.4 Biosensors 465

19.2.5 Theranostics 466

19.3 Final Remarks 467

References 467

Part V Lessons from Nature in Regenerative Medicine 471

20 Tissue Analogs by the Assembly of Engineered Hydrogel Blocks 473
Shilpa Sant, Daniela F. Coutinho, Nasser Sadr, Rui L. Reis, and Ali Khademhosseini

20.1 Introduction 473

20.2 Tissue/Organ Heterogeneity In Vivo 474

20.3 Hydrogel Engineering for Obtaining Biologically Inspired Structures 477

20.3.1 Structural Cues 477

20.3.2 Mechanical Cues 478

20.3.3 Biochemical Cues 480

20.3.4 Cell–Cell Contact 482

20.3.5 Combination of Multiple Cues 483

20.4 Assembly of Engineered Hydrogel Blocks 485

20.5 Conclusions 488

Acknowledgments 489

References 489

21 Injectable In-Situ-Forming Scaffolds for Tissue Engineering 495
Da Yeon Kim, Jae Ho Kim, Byoung Hyun Min, and Moon Suk Kim

21.1 Introduction 495

21.2 Injectable In-Situ-Forming Scaffolds Formed by Electrostatic Interactions 496

21.3 Injectable In-Situ-Forming Scaffolds Formed by Hydrophobic Interactions 497

21.4 Immune Response of Injectable In-Situ-Forming Scaffolds 500

21.5 Injectable In-Situ-Forming Scaffolds for Preclinical Regenerative Medicine 500

21.6 Conclusions and Outlook 501

References 502

22 Biomimetic Hydrogels for Regenerative Medicine 503
Iris Mironi-Harpaz, Olga Kossover, Eran Ivanir, and Dror Seliktar

22.1 Introduction 503

22.2 Natural and Synthetic Hydrogels 503

22.3 Hydrogel Properties 505

22.4 Engineering Strategies for Hydrogel Development 506

22.5 Applications in Biomedicine 508

References 511

23 Bio-inspired 3D Environments for Cartilage Engineering 515
José Luis Gómez Ribelles

23.1 Articular Cartilage Histology 515

23.2 Spontaneous and Forced Regeneration in Articular Cartilage 517

23.3 What Can Tissue Engineering Do for Articular Cartilage Regeneration? 517

23.4 Cell Sources for Cartilage Engineering 519

23.4.1 Bone Marrow Mesenchymal Cells Reaching the Cartilage Defect from Subchondral Bone 519

23.4.2 Autologous Mesenchymal Stem Cells from Different Sources 520

23.4.3 Mature Autologous Chondrocytes 521

23.5 The Role and Requirements of the Scaffolding Material 524

23.5.1 Gels Encapsulating Cells as Vehicles for Cell Transplant 524

23.5.2 Macroporous Scaffolds: Pore Architecture 524

23.5.3 Cell Adhesion Properties of the Scaffold Surfaces 525

23.5.4 Mechanical Properties 525

23.5.5 Can Scaffold Architecture Direct Tissue Organization? 526

23.5.6 Scaffold Biodegradation Rate 527

23.6 Growth Factor Delivery In Vivo 528

23.7 Conclusions 528

Acknowledgment 529

References 529

24 Soft Constructs for Skin Tissue Engineering 537
Simone S. Silva, Jo˜ao F. Mano, and Rui L. Reis

24.1 Introduction 537

24.2 Structure of Skin 537

24.2.1 Wound Healing 538

24.3 Current Biomaterials in Wound Healing 539

24.3.1 Alginate 539

24.3.2 Cellulose 540

24.3.3 Chitin/Chitosan 541

24.3.4 Hyaluronic Acid 543

24.3.5 Collagen and Other Proteins 544

24.3.6 Synthetic Polymers 545

24.4 Wound Dressings and Their Properties 545

24.5 Biomimetic Approaches in Skin Tissue Engineering 546

24.5.1 Commercially Available Skin Products 549

24.6 Final Remarks 549

Acknowledgments 552

List of Abbreviations 552

References 553

Index 559

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