The layer-by-layer (LbL) deposition technique is a versatile approach for preparing nanoscale multimaterial films: the fabrication of multicomposite films by the LbL procedure allows the combination of literally hundreds of different materials with nanometer thickness in a single device to obtain novel or superior performance. In the last 15 years the LbL technique has seen considerable developments and has now reached a point where it is beginning to find applications in bioengineering and biomedical engineering.
The book gives a thorough overview of applications of the LbL technique in the context of bioengineering and biomedical engineering where the last years have witnessed tremendous progress. The first part familiarizes the reader with the specifics of cell-film interactions that need to be taken into account for successful application of the LbL method in biological environments. The second part focuses on LbL-derived small drug delivery systems and antibacterial agents, and the third part covers nano- and microcapsules as drug carriers and biosensors. The fourth and last part focuses on larger-scale biomedical applications of the LbL method such as engineered tissues and implant coatings.

The layer-by-layer field has been exponentially growing since its beginning in the early 1990s as judged by the number of publications, communications at international conferences, and groups from around the world who are now contributing to developments in the field.Thanks to the enthusiasm and energy of Gero Decher and Joe Schlenoff, a first book on Multilayer Thin Films: Sequential Assembly of Composite Materials was published in 2006. In view of the great success of this book, the second edition of the book was edited in 2011, with a revision and extension to two volumes. As described in the online version, this book is “a comprehensive summary of layer-by-layer assembled, truly hybrid nanomaterials and thin films, covering organic, inorganic, colloidal, macromolecular, and biological components, as well as the assembly of nanoscale films derived from them on surfaces.” Today, the layer-by-layer field has spread to a large number of subfields, from the fundamental understanding of film growth and properties to applications in specific areas such as energy, functional coatings, and liquid and gas filtration. The idea for a complementary book specifically focused on biomedical applications arose in 2010, after several important developments in films, capsules, and free-standing membranes in relation to bioactive molecules, drug delivery, and tissue engineering. Several successful reviews were published during this period, which highlighted the possibilities of layer-by-layer films for biomedical applications.
In March 2011, a layer-by-layer symposium organized by Gero Decher and colleagues was held in Strasbourg, France, where it was highlighted that the biological applications of layer-by-layer materials were rapidly growing. In June 2014, a new symposium organized by Svetlana Sukhisvili and Mike Rubner gathered the community in Hoboken near New York. This meeting again highlighted the important developments in the biomedical field.
In this book, our aim is to show the wide potential of multilayers in the biomedical field and also to promote the potential of the technology among biomedical students, teachers, and researchers. We believe that this book may become a textbook for biomedical students and attract new groups to work in the field and to develop the field further. Future advancements in this area are to develop multilayers that can be effectively translated into the clinic and ultimately used to treat patients.
We are pleased to have edited this book. We are honored that so many contributors from all over the world have accepted our invitation and took time to write significant contributions.
We look forward to future exciting and fruitful developments of layer-by-layer assembled materials in the biomedical fields. We also believe that layer-by-layer assembly will complement the range of model materials for fundamental studies on cellular processes and will provide new and well-defined systems to contribute to the development of new therapeutic and imaging systems.

Foreword XVII

Preface XIX

About the Editors XXI

List of Contributors XXIII

Part I: Control of Cell/Film Interactions 1

1 Controlling Cell Adhesion Using pH-Modified Polyelectrolyte Multilayer Films 3

Marcus S. Niepel, Kristin Kirchhof, Matthias Menzel, Andreas Heilmann, and Thomas Groth

1.1 Introduction 3

1.2 Influence of pH-Modified PEM Films on Cell Adhesion and Growth 5

      1.2.1 HEP/CHI Multilayers 5

      1.2.2 PEI/HEP Multilayers 16

1.3 Summary and Outlook 24

Acknowledgments 25

References 25

2 The Interplay of Surface and Bulk Properties of Polyelectrolyte Multilayers in Determining Cell Adhesion 31

Joseph B. Schlenoff and Thomas C.S. Keller

2.1 Surface Properties 33

2.2 Bulk Modulus 38

References 42

3 Photocrosslinked Polyelectrolyte Films of Controlled Stiffness to Direct Cell Behavior 45

Naresh Saha, Claire Monge, Thomas Boudou, Catherine Picart, and Karine Glinel

3.1 Introduction 45

3.2 Elaboration of Homogeneous Films of Varying Rigidity 48

3.3 Elaboration of Rigidity Patterns 52

3.4 Behavior of Mammalian Cells on Homogeneous and Photopatterned Films 54

3.5 Influence of Film Rigidity on Bacterial Behavior 58

3.6 Conclusion 61

Acknowledgments 61

References 62

4 Nanofilm Biomaterials: Dual Control of Mechanical and Bioactive Properties 65

Emmanuel Pauthe and Paul R. Van Tassel

4.1 Introduction 65

4.2 Surface Cross-Linking 67

4.3 NP Templating 69

4.4 Discussion 73

4.5 Conclusions 75

Acknowledgments 75

References 75

5 Bioactive and Spatially Organized LbL Films 79

Zhengwei Mao, Shan Yu, and Changyou Gao

5.1 Introduction 79

5.2 Role of Chemical Properties 80

      5.2.1 Bulk Composition 80

      5.2.1.1 Introducing Natural Polyelectrolytes as Building Blocks 80

      5.2.1.2 Incorporating Hormones and Growth Factors 81

      5.2.2 Surface Chemistry 83

      5.2.2.1 Role of the Final Layer 83

      5.2.2.2 Surface Modification with Cell Binding Molecules 83

5.3 Role of Physical Properties 85

      5.3.1 Mechanical Property 85

      5.3.1.1 Chemical Cross-linking 86

      5.3.1.2 Incorporating Stiff Building Blocks 86

      5.3.1.3 Control Environmental pH or Salt Concentration 87

      5.3.2 Topography 89

5.4 Spatially Organized PEMs 89

      5.4.1 Patterned PEMs 89

      5.4.2 Gradient PEMs 91

5.5 Conclusions and Future Perspectives 92

Acknowledgments 94

References 94

6 Controlling Stem Cell Adhesion, Proliferation, and Differentiation with Layer-by-Layer Films 103

Stewart Wales, Guak-Kim Tan, and Justin J. Cooper-White

6.1 Introduction 103

      6.1.1 Types of Stem Cells 103

      6.1.2 Stem Cell Fate Choices 104

      6.1.3 The Stem Cell “Niche” 104

      6.1.3.1 Soluble Factors 105

      6.1.3.2 Cell–Cell Interactions 105

      6.1.3.3 Cell–ECM Interactions 106

      6.1.4 Influencing Stem Cell Fate Choice 106

6.2 Mesenchymal Stem Cells and Layer-by-Layer Films 107

      6.2.1 Human MSC Adhesion, Proliferation, and Differentiation 107

      6.2.2 Murine MSC Adhesion, Proliferation, and Differentiation 114

6.3 Pluripotent Stem Cells and Layer-by-Layer Films 116

      6.3.1 Murine ESC Adhesion, Proliferation, and Maintenance of Potency 117

      6.3.2 Murine ESC Differentiation 120

      6.3.3 Human ESC Adhesion, Proliferation, and Differentiation 122

6.4 Future Directions and Trends 123

References 124

Part II: Delivery of Small Drugs, DNA and siRNA 131

7 Engineering Layer-by-Layer Thin Films for Multiscale and Multidrug Delivery Applications 133

Nisarg J. Shah, Bryan B. Hsu, Erik C. Dreaden, and Paula T. Hammond

7.1 Introduction 133

      7.1.1 The Promise of LbL Delivery 133

      7.1.1.1 High Drug Density and Scalability 133

      7.1.1.2 Translatable to 2D and 3D Geometries 133

      7.1.1.3 Facile Encapsulation of Active Biologics 134

      7.1.1.4 Multiple Drug Combinations 134

      7.1.1.5 Controlled Time-Dependent Release and Opportunity for Multisequence Release 134

      7.1.2 Growth in the LbL Delivery Field 135

      7.1.3 Brief Outline of Chapter 135

7.2 Engineering LbL Release Mechanisms – from Fast to Slow Release 136

      7.2.1 Overview 136

      7.2.2 Tuning Hydrolytic Release 137

      7.2.3 Small Molecule Release 139

      7.2.3.1 Direct Adsorption of Charged Molecules 139

      7.2.3.2 Complexation with Charged Polymer 139

      7.2.3.3 Pre-encapsulation in Carrier 141

      7.2.4 H-Bond-Based Release of Molecules 141

      7.2.5 Impact of Assembly Approach and Spray-LbL 142

      7.2.6 Other Mechanisms of Release 143

      7.2.7 Controlling Release Kinetics and Manipulating Sequential Release 144

7.3 LbL Biologic Release for Directing Cell Behavior 145

      7.3.1 Overview 145

      7.3.2 Controlled Growth Factor Delivery for Tissue Engineering 146

      7.3.2.1 Release of Therapeutic Growth Factors from LbL Films 146

      7.3.3 Growth Factor Delivery with Synergistic Impact 148

      7.3.3.1 BMP-2 and VEGF 148

      7.3.3.2 Implant Osseointegration: The Synergistic Effect of BMP-2 and Hydroxyapatite 149

      7.3.4 Staggering Release of Drugs from LbL Films with “Barrier” Layers 151

      7.3.5 Nucleic Acid Delivery as a Modulator of Cell Response 152

      7.3.5.1 Challenges of DNA/siRNA Release for Localized Delivery 152

      7.3.5.2 Multilayer Polymer “Tattoos” for DNA-Based Vaccination 153

      7.3.5.3 Wound Healing Mediated by siRNA for Sustained Localized Knockdown 154

7.4 Moving LbL Release Technologies to the Nanoscale: LbL Nanoparticles 156

      7.4.1 Overview – Nanoparticle Delivery Challenges 156

      7.4.2 Tuning LbL Systems for Systemic Delivery – Stability, Blood Half-life 156

      7.4.3 Adapting LbL Nanoparticles for Targeting 158

      7.4.3.1 Tumor Microenvironment, Hypoxic Response 159

      7.4.3.2 Molecular Targeting 160

      7.4.4 Dual Drug Combinations 160

      7.4.4.1 siRNA Chemotherapy Combination Nanoparticle Systems 161

      7.4.4.2 Future Potential 162

7.5 Conclusions and Perspective on Future Directions 162

      7.5.1 Translation of Technologies 163

Acknowledgments 165

References 165

8 Polyelectrolyte Multilayer Coatings for the Release and Transfer of Plasmid DNA 171

David M. Lynn

8.1 Introduction 171

8.2 Fabrication of Multilayers Using Plasmid DNA and Hydrolytically Degradable Polyamines 173

8.3 Toward Therapeutic Applications In vivo Contact-Mediated Approaches to Vascular Gene Delivery 178

      8.3.1 Transfer of DNA to Arterial Tissue Using Film-Coated Intravascular Stents 178

      8.3.2 Transfer of DNA to Arterial Tissue Using Film-Coated Balloon Catheters 180

      8.3.3 Beyond Reporter Genes: Approaches to the Reduction of Intimal Hyperplasia in Injured Arteries 182

      8.3.4 Other Potential Applications 184

8.4 Exerting Temporal Control over the Release of DNA 184

      8.4.1 New Polymers and Principles: Degradable Polyamines and “Charge Shifting” Cationic Polymers 185

      8.4.2 Multicomponent Multilayers for the Release of Multiple DNA Constructs 187

      8.4.2.1 Approaches to Promoting the Rapid Release of DNA 188

8.5 Concluding Remarks 190

Acknowledgments 190

References 191

9 LbL-Based Gene Delivery: Challenges and Promises 195

Joelle Ogier

9.1 LbL-DNA Delivery 195

      9.1.1 Pioneer Designs 196

      9.1.2 DNA Spatial and Temporal Scheduled Delivery 199

      9.1.3 Pending Challenges: From In Vitro Substrate-Mediated Gene Delivery to In Vivo Formulations 201

9.2 LbL-siRNA Delivery 202

9.3 Concluding Remarks 204

References 205

10 Subcompartmentalized Surface-Adhering Polymer Thin Films Toward Drug Delivery Applications 207

Boon M. Teo, Martin E. Lynge, Leticia Hosta-Rigau, and Brigitte Städler

10.1 Introduction 207

10.2 Cyclodextrin (CD)-Containing LbL Films 208

      10.2.1 Assembly 209

      10.2.2 Drug Delivery Applications 209

10.3 Block Copolymer Micelle (BCM)-Containing LbL Films 212

      10.3.1 Assembly 213

      10.3.1.1 Glassy BCMs within LbL Films 213

      10.3.1.2 Temperature and pH Responsive BCMs within LbL Films 213

      10.3.2 Drug Delivery Applications 215

10.4 Liposome-Containing LbL Films 215

      10.4.1 Assembly 216

      10.4.2 Cargo Release Capability from Liposomes within LbL Films 219

      10.4.3 Drug Delivery Applications 219

10.5 LbL Films Containing Miscellaneous Drug Deposits 222

10.6 Conclusion/Outlook 224

References 225

Part III: Nano- and Microcapsules as Drug Carriers 233

11 Multilayer Capsules for In vivo Biomedical Applications 235

Bruno G. De Geest and Stefaan De Koker

11.1 Introduction 235

11.2 A Rationale for Functionally Engineered Multilayer Capsules 236

      11.2.1 General Considerations 236

      11.2.2 Multilayer Capsules Responding to Physicochemical and Physiological Stimuli 238

11.3 In vivo Fate of Multilayer Capsules 241

      11.3.1 Tissue Response 241

      11.3.2 In vivo Uptake and Degradation 243

      11.3.3 Blood Circulation 245

11.4 Vaccine Delivery via Multilayer Capsules 246

11.5 Tumor Targeting via Multilayer Capsules 252

11.6 Concluding Remarks 253

References 254

12 Light-Addressable Microcapsules 257

Markus Ochs, Wolfgang J. Parak, Joanna Rejman, and Susana Carregal-Romero

12.1 Introduction 257

      12.2 Light-Responsive Components 258

      12.2.1 Light-Responsive Polyelectrolytes and Molecules 258

      12.2.2 Light-Responsive Shells 259

      12.2.3 Light-Responsive Nanoparticles 259

12.3 Capsule Synthesis and Loading 261

12.4 Gold-Modified Layer-by-Layer Capsules 264

12.5 Morphological Changes of Capsules and Nanoparticles 267

12.6 Bubble Formation 267

12.7 Cytosolic Release 269

12.8 Triggering Cytosolic Reactions 272

12.9 Conclusions and Perspectives 274

Acknowledgments 275

References 275

13 Nanoparticle Functionalized Surfaces 279

Mihaela Delcea, Helmuth Moehwald, and Andre G. Skirtach

13.1 Introduction 279

13.2 Nanoparticles on Polyelectrolyte Multilayer LbL Capsules 281

      13.2.1 Adsorption of Nanoparticles onto Polyelectrolyte Multilayer Capsules 281

      13.2.2 Light- and Magnetic-Field-Induced Permeability Control 282

      13.2.3 Fluorescence Imaging Using Quantum Dots 284

      13.2.4 Magnetic Nanoparticles: Activation and Targeting 284

      13.2.5 Catalysis Using Nanoparticles 285

      13.2.6 Enhancement of Mechanical Properties of Capsules 285

      13.2.7 Anisotropic Capsules 286

13.3 Nanoparticles on Polyelectrolyte LbL Films 287

      13.3.1 LbL Films and Adsorption of Nanoparticles onto Films 287

      13.3.2 Laser Activation 287

      13.3.3 Fluorescent Labeling of Films 289

      13.3.4 Increasing the Stiffness of Films for Cell Adhesion and Control over Asymmetric Particle Fabrication 289

      13.3.5 Additional Functionalities through Addition of Nanoparticles 290

13.4 Conclusions 290

References 292

14 Layer-by-Layer Microcapsules Based on Functional Polysaccharides 295

Anna Szarpak-Jankowska, Jing Jing, and Rachel Auzély-Velty

14.1 Introduction 295

14.2 Fabrication of Polysaccharide Capsules by the LbL Technique 296

      14.2.1 Natural Charged Polysaccharides Used in LbL Capsules 296

      14.2.2 General Methods for the Assembly of Polysaccharides into LbL Capsules 297

      14.2.3 Cross-Linking of the Polysaccharide Shells 298

      14.2.4 Functional Multilayer Shells Based on Chemically Modified Polysaccharides 300

      14.2.4.1 Multilayer Shells Made of Alkylated Hyaluronic Acid 300

      14.2.4.2 Multilayer Shells Made of Hyaluronic Acid and Dextran Bearing Pendant Cyclodextrins Along the Chain 300

      14.2.4.3 Multilayer Shells Made of Quaternized Chitosan 301

14.3 Biomedical Applications 302

14.4 Interactions with Living Cells 305

14.5 Conclusion 306

References 307

15 Nanoengineered Polymer Capsules: Moving into the Biological Realm 309

Katelyn T. Gause, Yan Yan, and Frank Caruso

15.1 Introduction 309

15.2 Capsule Design and Assembly 310

      15.2.1 Templates 310

      15.2.2 Materials and Assembly Interactions 312

      15.2.2.1 Electrostatic Assembly 312

      15.2.2.2 Hydrogen Bonding-Facilitated Assembly 312

      15.2.2.3 DNA Base Pairing 313

      15.2.2.4 “Click” Assembly and Cross-linking 314

      15.2.3 Cargo Encapsulation 315

      15.2.3.1 Preloading 316

      15.2.3.2 Postloading 317

      15.2.3.3 Cargo within Capsule Shells 317

      15.2.4 Biological Stimuli-Responsive Cargo Release 318

      15.2.4.1 Enzymatically Responsive Cargo Release 318

      15.2.4.2 pH-Responsive Cargo Release 319

      15.2.4.3 Redox-Responsive Cargo Release 320

15.3 Capsules at the Biological Interface 321

      15.3.1 Circulation and Biodistribution 322

      15.3.2 Cellular Interactions 323

      15.3.3 Intracellular Trafficking 324

15.4 Biological Applications 326

      15.4.1 Anticancer Drug Delivery 326

      15.4.1.1 Targeting 326

      15.4.2 Vaccine Delivery 329

      15.4.3 Biosensors and Bioreactors 331

15.5 Conclusion and Outlook 335

References 336

16 Biocompatible and Biogenic Microcapsules 343

Jie Zhao, Jinbo Fei, and Junbai Li

16.1 Introduction 343

16.2 LbL Assembly of Biocompatible and Biogenic Microcapsules 344

      16.2.1 Lipid-Based Microcapsules 344

      16.2.2 Polysaccharide-Based Microcapsules 346

      16.2.3 Protein-Based Microcapsules 348

16.3 Applications 349

      16.3.1 Drug Carriers for Cancer Treatment 350

      16.3.1.1 Methods for Drug Loading 350

      16.3.1.2 Thermotherapy 352

      16.3.1.3 Photodynamic Therapy 354

      16.3.2 Blood Substitutes 356

16.4 Conclusions and Perspectives 358

Acknowledgments 358

References 358

17 Three-Dimensional Multilayered Devices for Biomedical Applications 363

Rui R. Costa and João F. Mano

17.1 Introduction 363

17.2 Freestanding Multilayer Films 364

      17.2.1 Pure Freestanding Membranes 364

      17.2.2 Hybrid LbL-Assisted Techniques 366

17.3 Tubular Structures 366

17.4 Spherical Coated Shapes 368

      17.4.1 Drug Carriers 369

      17.4.2 Biosensors 371

17.5 Complex LbL Devices with Compartmentalization and Hierarchical Components 372

      17.5.1 Confined Chemical Reactions 373

      17.5.2 Customized Multifunctional Reactors 374

17.6 Porous Structures 376

17.7 Conclusions 377

Acknowledgments 378

References 378

Part IV: Engineered Tissues and Coatings of Implants 385

18 Polyelectrolyte Multilayer Film – A Smart Polymer for Vascular Tissue Engineering 387

Patrick Menu and Halima Kerdjoudj

18.1 Layer by Layer Coating 388

18.2 Anti-Adhesive Properties of PEMs 388

18.3 Adhesion Properties of PEMs and Their Use in Vascular Tissue Engineering 389

18.4 Polyelectrolyte Multilayer Films and Stem Cell Behavior 390

18.5 PEM Coating of Vascular Prosthesis 391

18.6 Functional PEMs Mimicking Endothelial Cell Function 391

18.7 Conclusion 392

References 392

19 Polyelectrolyte Multilayers as Robust Coating for Cardiovascular Biomaterials 399

Kefeng Ren and Jian Ji

19.1 Introduction 399

19.2 The Basement Membrane: The Bioinspired Cue for Cardiovascular Regeneration 400

19.3 PEMs as a Feasible Method for Immobilization: From Antithrombosis to the Synergistic Interaction 401

19.4 Controlled Delivery from PEMs: From Small Molecule Drugs and Bioactive Molecules to Genes 403

19.5 Effects of Mechanical Properties of PEMs on Cellular Events 406

19.6 PEM as a Coating for Cardiovascular Device: From In vitro to In vivo 407

19.7 Conclusion and Perspectives 412

References 412

20 LbL Nanofilms Through Biological Recognition for 3D Tissue Engineering 419

Michiya Matsusaki and Mitsuru Akashi

20.1 Introduction 419

20.2 A Bottom-Up Approach for 3D Tissue Construction 421

      20.2.1 Hierarchical Cell Manipulation Technique 422

      20.2.1.1 Fabrication of Multilayered Structure by Nano-ECM Coating 423

      20.2.1.2 Effect of Nanofilms on Cellular Function 426

      20.2.1.3 Control of Cellular Function and Activity in 3D Environments 426

      20.2.1.4 Permeability Assay of Multilayered Fibrous Tissues 431

      20.2.2 Blood Vessel Wall Model 432

      20.2.2.1 Construction of Blood Vessel Wall Model 433

      20.2.2.2 Quantitative 3D Analysis of Nitric Oxide Using Blood Vessel Wall Model 433

      20.2.3 Blood Capillary Model 436

      20.2.3.1 Fabrication of Blood Capillary Model by Cell-Accumulation Technique 436

      20.2.3.2 Application for the Evaluation of the Interaction with Tissues 438

      20.2.4 Perfusable Blood Vessel Channel Model 439

      20.2.4.1 Construction of Blood Vessel Channel Model in Hydrogel 441

      20.2.4.2 In vitro Permeability Assay 442

      20.2.5 Engineering 3D Tissue Chips by Inkjet Cell Printing 442

      20.2.5.1 Cell and ECM Printing 445

      20.2.5.2 Human Liver Tissue Chips and Liver Function Assay 445

20.3 Conclusions 447

Acknowledgments 447

References 447

21 Matrix-Bound Presentation of Bone Morphogenetic Protein 2 by Multilayer Films: Fundamental Studies and Applications to Orthopedics 453

Flora Gilde, Raphael Guillot, Laure Fourel, Jorge Almodovar, Thomas Crouzier, Thomas Boudou, and Catherine Picart

21.1 Introduction 453

21.2 BMP-2 Loading: Physico-Chemistry and Secondary Structure 455

      21.2.1 Tunable Parameters for BMP-2 Loading 455

      21.2.2 Secondary Structure of BMP-2 in Hydrated and Dry Films 458

      21.2.2.1 Secondary Structure of BMP-2 in Solution 458

      21.2.2.2 Structure of BMP-2 Trapped in Hydrated or Dry (PLL/HA) Films 459

21.3 Osteoinductive Properties of Matrix-Bound BMP-2 In vitro 461

21.4 Early Cytoskeletal Effects of BMP-2 463

21.5 Toward In vivo Applications for Bone Repair 467

      21.5.1 Characterization of PEM Film Deposition on TCP/HAP Granules and on Porous Titanium 467

      21.5.2 Sterilization by γ-Irradiation 469

      21.5.3 Osteoinduction In vivo 471

21.6 Toward Spatial Control of Differentiation 475

21.7 Conclusions 477

Acknowledgments 478

List of Abbreviations 478

References 479

22 Polyelectrolyte Multilayers for Applications in Hepatic Tissue Engineering 487

Margaret E. Cassin and Padmavathy Rajagopalan

22.1 Introduction 487

      22.1.1 The Liver 489

      22.1.2 Hepatic Tissue Engineering 491

      22.1.3 PEMs and Hepatic Tissue Engineering 491

22.2 PEMs for 2D Hepatic Cell Cultures 492

      22.2.1 Tuning Mechanical and Chemical Properties of PEMs 492

22.3 PEMs for 3D Hepatic Cell Cultures 495

      22.3.1 PEMs that Mimic the Space of Disse 495

      22.3.2 Porous Scaffolds for Hepatic Cell Cultures 496

      22.3.3 3D PEM Stamping for Primary Hepatocyte Co-cultures 498

22.4 Conclusions 498

Acknowledgments 498

References 499

23 Polyelectrolyte Multilayer Film for the Regulation of Stem Cells in Orthopedic Field 507

Yan Hu and Kaiyong Cai

23.1 Introduction 507

23.2 Layer-by-Layer Assembly and Classification 508

23.3 Classic Polyelectrolyte Multilayer Films (Intermediate Layer) 509

      23.3.1 Bioactive Multilayer Films 509

      23.3.1.1 Compositions of Polyelectrolyte Multilayer Films 510

      23.3.1.2 Stiffness of Polyelectrolyte Multilayer Films 511

      23.3.1.3 Cell Specific Recognition of Polyelectrolyte Multilayer Films 511

      23.3.2 Gene-Activating Multilayer Film 512

23.4 Hybrid Polyelectrolyte Multilayer Film 514

      23.4.1 Growth Factors or Cytokines Embedding Hybrid Layer 515

      23.4.2 Drug Embedding Hybrid Layer 516

      23.4.3 Nanoparticles Embedding Hybrid Layer 518

23.5 “Protecting” Polyelectrolyte Multilayer Film (Cover Layer) 518

23.6 Conclusion and Perspective 521

References 521

24 Axonal Regeneration and Myelination: Applicability of the Layer-by-Layer Technology 525

Chun Liu, Ryan Pyne, Seungik Baek, Jeffrey Sakamoto, Mark H. Tuszynski, and Christina Chan

24.1 Current Challenges of Spinal Cord Injury: Inflammation, Axonal Regeneration, and Remyelination 525

      24.1.1 Spinal Cord Injury 525

      24.1.2 Potential of Tissue Engineering for Treating SCI 527

24.2 PEM Film–Cell Interactions and Adhesion 530

      24.2.1 Polyelectrolyte Multilayers in Tissue Engineering 531

      24.2.2 Components of the Multilayers 532

      24.2.3 LbL as an Adhesive Coating for Neural Cell Attachment 533

      24.2.4 Patterned Co-cultures Using LbL Technique 534

24.3 Controlled Drug Delivery for Nerve Regeneration 536

      24.3.1 Drug Release from LbL Films 536

      24.3.2 Local Drug Release for Neural Regeneration 537

24.4 Future Perspective 538

Acknowledgments 539

References 539

Index 547

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