Main description:

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.

Contents:

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 Stadler 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 Auzely-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 Joao 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 -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