Layer-by-Layer Films for Biomedical Applications
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More About This Title Layer-by-Layer Films for Biomedical Applications

English

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.

English

Catherine Picart is full Professor of Bioengineering and Biomaterials at the Grenoble Institute of Technology, France, and former junior member of the Institut Universitaire de France (2006-2011). She obtained her PhD in Biomedical Engineering from the University Joseph Fourier, Grenoble, and did post-doctoral research at the University of Pennsylvania, USA. Afterwards she joined the University Louis Pasteur, Strasbourg, as Assistant Professor and later the Department of Biology and Health at the University of Montpellier 2 as Associate Professor. Catherine Picart's research focuses on the assembly of biopolymers, protein/lipid interactions, and musculo-skeletal tissue engineering. She has authored more than 90 original articles and 6 reviews in international peer-reviewed journals. She received two ERC Grants from the European Research Council: a starting grant at the consolidator stage in 2010 and a Proof of Concept in 2012 to further develop osteoinductive layer-by-layer films for orthopedic and dental clinical applications. In 2013, she was nominated "Chevalier de l'ordre National du Merite" by the French Ministry of Research

Frank Caruso is a Professor in the Department of Chemical and Biomolecular Engineering at the University of Melbourne, Australia. He was awarded an Australian Research Council Laureate Fellowship 2012 for recognition of his significant leadership and mentoring role in building Australia's internationally competitive research capacity. He has published over 350 peer-reviewed papers and is on ISI's most highly cited list, ranking in the top 20 worldwide in materials science in 2011. Frank Caruso is also included in Thomson Reuters' 2014 World's Most influential scientific minds. He was elected a Fellow of the Australian Academy of Science in 2009. Prof. Caruso is also the recipient of the inaugural 2012 ACS Nano Lectureship Award (Asia/Pacific) from the American Chemical Society for global impact in nanoscience and nanotechnology, the 2013 Australian Museum CSIRO Eureka Prize for Scientific Leadership, and the 2014 Victoria Prize for Science and Innovation. His research interests focus on developing advanced nano- and biomaterials for biotechnology and medicine.

Jean-Claude Voegel was until end of 2012 head of the INSERM (French National Institute for Health and Medical Research) research unit "Biomaterials and Tissue Engineering" at the University of Strasbourg, France. His scientific activities were based on a research project going from fundamental developments to clinical applications, the preparation of materials and modification of biomaterial surfaces using functionalized architectures mainly prepared with the aid of polyelectrolyte multilayers obtained by the LbL technology. Jean-Claude Voegel published more than 130 papers in high-impact factor journals in the last decade around these projects and belongs to the top scientists in chemistry and materials science in terms of citations in this field.

English

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

5.2.2 Surface Chemistry 83

5.3 Role of Physical Properties 85

5.3.1 Mechanical Property 85

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 StemCell 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

6.1.4 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

7.1.2 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

7.2.4 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

7.3.3 Growth Factor Delivery with Synergistic Impact 148

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

7.4 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

7.4.4 Dual Drug Combinations 160

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

8.5 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

10.3.2 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-AddressableMicrocapsules 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

14.3 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

15.2.3 Cargo Encapsulation 315

15.2.4 Biological Stimuli-Responsive Cargo Release 318

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

15.4.2 Vaccine Delivery 329

15.4.3 Biosensors and Bioreactors 331

15.5 Conclusion and Outlook 335

References 336

16 Biocompatible and BiogenicMicrocapsules 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

16.3.2 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 andMitsuru Akashi

20.1 Introduction 419

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

20.2.1 Hierarchical Cell Manipulation Technique 422

20.2.2 Blood VesselWall Model 432

Model 433

20.2.3 Blood Capillary Model 436

20.2.4 Perfusable Blood Vessel Channel Model 439

20.2.5 Engineering 3D Tissue Chips by Inkjet Cell Printing 442

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

21.3 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

23.3.2 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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