Layer-by-Layer Films for Biomedical Applications -- Contents -- Foreword -- Preface -- About the Editors -- List of Contributors -- Part I: Control of Cell/Film Interactions -- Chapter 1 Controlling Cell Adhesion Using pH-Modified Polyelectrolyte Multilayer Films -- 1.1 Introduction -- 1.2 Influence of pH-Modified PEM Films on Cell Adhesion and Growth -- 1.2.1 HEP/CHI Multilayers -- 1.2.2 PEI/HEP Multilayers -- 1.3 Summary and Outlook -- Acknowledgments -- References -- Chapter 2 The Interplay of Surface and Bulk Properties of Polyelectrolyte Multilayers in Determining Cell Adhesion -- 2.1 Surface Properties -- 2.2 Bulk Modulus -- References -- Chapter 3 Photocrosslinked Polyelectrolyte Films of Controlled Stiffness to Direct Cell Behavior -- 3.1 Introduction -- 3.2 Elaboration of Homogeneous Films of Varying Rigidity -- 3.3 Elaboration of Rigidity Patterns -- 3.4 Behavior of Mammalian Cells on Homogeneous and Photopatterned Films -- 3.5 Influence of Film Rigidity on Bacterial Behavior -- 3.6 Conclusion -- Acknowledgments -- References -- Chapter 4 Nanofilm Biomaterials: Dual Control of Mechanical and Bioactive Properties -- 4.1 Introduction -- 4.2 Surface Cross-Linking -- 4.3 NP Templating -- 4.4 Discussion -- 4.5 Conclusions -- Acknowledgments -- References -- Chapter 5 Bioactive and Spatially Organized LbL Films -- 5.1 Introduction -- 5.2 Role of Chemical Properties -- 5.2.1 Bulk Composition -- 5.2.1.1 Introducing Natural Polyelectrolytes as Building Blocks -- 5.2.1.2 Incorporating Hormones and Growth Factors -- 5.2.2 Surface Chemistry -- 5.2.2.1 Role of the Final Layer -- 5.2.2.2 Surface Modification with Cell Binding Molecules -- 5.3 Role of Physical Properties -- 5.3.1 Mechanical Property -- 5.3.1.1 Chemical Cross-linking -- 5.3.1.2 Incorporating Stiff Building Blocks.

5.3.1.3 Control Environmental pH or Salt Concentration -- 5.3.2 Topography -- 5.4 Spatially Organized PEMs -- 5.4.1 Patterned PEMs -- 5.4.2 Gradient PEMs -- 5.5 Conclusions and Future Perspectives -- Acknowledgments -- References -- Chapter 6 Controlling Stem Cell Adhesion, Proliferation, and Differentiation with Layer-by-Layer Films -- 6.1 Introduction -- 6.1.1 Types of Stem Cells -- 6.1.2 Stem Cell Fate Choices -- 6.1.3 The Stem Cell ``Niche'' -- 6.1.3.1 Soluble Factors -- 6.1.3.2 Cell-Cell Interactions -- 6.1.3.3 Cell-ECM Interactions -- 6.1.4 Influencing Stem Cell Fate Choice -- 6.2 Mesenchymal Stem Cells and Layer-by-Layer Films -- 6.2.1 Human MSC Adhesion, Proliferation, and Differentiation -- 6.2.2 Murine MSC Adhesion, Proliferation, and Differentiation -- 6.3 Pluripotent Stem Cells and Layer-by-Layer Films -- 6.3.1 Murine ESC Adhesion, Proliferation, and Maintenance of Potency -- 6.3.2 Murine ESC Differentiation -- 6.3.3 Human ESC Adhesion, Proliferation, and Differentiation -- 6.4 Future Directions and Trends -- References -- Part II: Delivery of Small Drugs, DNA and siRNA -- Chapter 7 Engineering Layer-by-Layer Thin Films for Multiscale and Multidrug Delivery Applications -- 7.1 Introduction -- 7.1.1 The Promise of LbL Delivery -- 7.1.1.1 High Drug Density and Scalability -- 7.1.1.2 Translatable to 2D and 3D Geometries -- 7.1.1.3 Facile Encapsulation of Active Biologics -- 7.1.1.4 Multiple Drug Combinations -- 7.1.1.5 Controlled Time-Dependent Release and Opportunity for Multisequence Release -- 7.1.2 Growth in the LbL Delivery Field -- 7.1.3 Brief Outline of Chapter -- 7.2 Engineering LbL Release Mechanisms - from Fast to Slow Release -- 7.2.1 Overview -- 7.2.2 Tuning Hydrolytic Release -- 7.2.3 Small Molecule Release -- 7.2.3.1 Direct Adsorption of Charged Molecules.

7.2.3.2 Complexation with Charged Polymer -- 7.2.3.3 Pre-encapsulation in Carrier -- 7.2.4 H-Bond-Based Release of Molecules -- 7.2.5 Impact of Assembly Approach and Spray-LbL -- 7.2.6 Other Mechanisms of Release -- 7.2.7 Controlling Release Kinetics and Manipulating Sequential Release -- 7.3 LbL Biologic Release for Directing Cell Behavior -- 7.3.1 Overview -- 7.3.2 Controlled Growth Factor Delivery for Tissue Engineering -- 7.3.2.1 Release of Therapeutic Growth Factors from LbL Films -- 7.3.3 Growth Factor Delivery with Synergistic Impact -- 7.3.3.1 BMP-2 and VEGF -- 7.3.3.2 Implant Osseointegration: The Synergistic Effect of BMP-2 and Hydroxyapatite -- 7.3.4 Staggering Release of Drugs from LbL Films with ``Barrier'' Layers -- 7.3.5 Nucleic Acid Delivery as a Modulator of Cell Response -- 7.3.5.1 Challenges of DNA/siRNA Release for Localized Delivery -- 7.3.5.2 Multilayer Polymer ``Tattoos'' for DNA-Based Vaccination -- 7.3.5.3 Wound Healing Mediated by siRNA for Sustained Localized Knockdown -- 7.4 Moving LbL Release Technologies to the Nanoscale: LbL Nanoparticles -- 7.4.1 Overview - Nanoparticle Delivery Challenges -- 7.4.2 Tuning LbL Systems for Systemic Delivery - Stability, Blood Half-life -- 7.4.3 Adapting LbL Nanoparticles for Targeting -- 7.4.3.1 Tumor Microenvironment, Hypoxic Response -- 7.4.3.2 Molecular Targeting -- 7.4.4 Dual Drug Combinations -- 7.4.4.1 siRNA Chemotherapy Combination Nanoparticle Systems -- 7.4.4.2 Future Potential -- 7.5 Conclusions and Perspective on Future Directions -- 7.5.1 Translation of Technologies -- Acknowledgments -- References -- Chapter 8 Polyelectrolyte Multilayer Coatings for the Release and Transfer of Plasmid DNA -- 8.1 Introduction.

8.2 Fabrication of Multilayers Using Plasmid DNA and Hydrolytically Degradable Polyamines -- 8.3 Toward Therapeutic Applications In vivo Contact-Mediated Approaches to Vascular Gene Delivery -- 8.3.1 Transfer of DNA to Arterial Tissue Using Film-Coated Intravascular Stents -- 8.3.2 Transfer of DNA to Arterial Tissue Using Film-Coated Balloon Catheters -- 8.3.3 Beyond Reporter Genes: Approaches to the Reduction of Intimal Hyperplasia in Injured Arteries -- 8.3.4 Other Potential Applications -- 8.4 Exerting Temporal Control over the Release of DNA -- 8.4.1 New Polymers and Principles: Degradable Polyamines and ``Charge Shifting'' Cationic Polymers -- 8.4.2 Multicomponent Multilayers for the Release of Multiple DNA Constructs -- 8.4.2.1 Approaches to Promoting the Rapid Release of DNA -- 8.5 Concluding Remarks -- Acknowledgments -- References -- Chapter 9 LbL-Based Gene Delivery: Challenges and Promises -- 9.1 LbL-DNA Delivery -- 9.1.1 Pioneer Designs -- 9.1.2 DNA Spatial and Temporal Scheduled Delivery -- 9.1.3 Pending Challenges: From In Vitro Substrate-Mediated Gene Delivery to In Vivo Formulations -- 9.2 LbL-siRNA Delivery -- 9.3 Concluding Remarks -- References -- Chapter 10 Subcompartmentalized Surface-Adhering Polymer Thin Films Toward Drug Delivery Applications -- 10.1 Introduction -- 10.2 Cyclodextrin (CD)-Containing LbL Films -- 10.2.1 Assembly -- 10.2.2 Drug Delivery Applications -- 10.3 Block Copolymer Micelle (BCM)-Containing LbL Films -- 10.3.1 Assembly -- 10.3.1.1 Glassy BCMs within LbL Films -- 10.3.1.2 Temperature and pH Responsive BCMs within LbL Films -- 10.3.2 Drug Delivery Applications -- 10.4 Liposome-Containing LbL Films -- 10.4.1 Assembly -- 10.4.2 Cargo Release Capability from Liposomes within LbL Films -- 10.4.3 Drug Delivery Applications.

10.5 LbL Films Containing Miscellaneous Drug Deposits -- 10.6 Conclusion/Outlook -- References -- Part III: Nano- and Microcapsules as Drug Carriers -- Chapter 11 Multilayer Capsules for In vivo Biomedical Applications -- 11.1 Introduction -- 11.2 A Rationale for Functionally Engineered Multilayer Capsules -- 11.2.1 General Considerations -- 11.2.2 Multilayer Capsules Responding to Physicochemical and Physiological Stimuli -- 11.3 In vivo Fate of Multilayer Capsules -- 11.3.1 Tissue Response -- 11.3.2 In vivo Uptake and Degradation -- 11.3.3 Blood Circulation -- 11.4 Vaccine Delivery via Multilayer Capsules -- 11.5 Tumor Targeting via Multilayer Capsules -- 11.6 Concluding Remarks -- References -- Chapter 12 Light-Addressable Microcapsules -- 12.1 Introduction -- 12.2 Light-Responsive Components -- 12.2.1 Light-Responsive Polyelectrolytes and Molecules -- 12.2.2 Light-Responsive Shells -- 12.2.3 Light-Responsive Nanoparticles -- 12.3 Capsule Synthesis and Loading -- 12.4 Gold-Modified Layer-by-Layer Capsules -- 12.5 Morphological Changes of Capsules and Nanoparticles -- 12.6 Bubble Formation -- 12.7 Cytosolic Release -- 12.8 Triggering Cytosolic Reactions -- 12.9 Conclusions and Perspectives -- Acknowledgments -- References -- Chapter 13 Nanoparticle Functionalized Surfaces -- 13.1 Introduction -- 13.2 Nanoparticles on Polyelectrolyte Multilayer LbL Capsules -- 13.2.1 Adsorption of Nanoparticles onto Polyelectrolyte Multilayer Capsules -- 13.2.2 Light- and Magnetic-Field-Induced Permeability Control -- 13.2.3 Fluorescence Imaging Using Quantum Dots -- 13.2.4 Magnetic Nanoparticles: Activation and Targeting -- 13.2.5 Catalysis Using Nanoparticles -- 13.2.6 Enhancement of Mechanical Properties of Capsules -- 13.2.7 Anisotropic Capsules -- 13.3 Nanoparticles on Polyelectrolyte LbL Films.

13.3.1 LbL Films and Adsorption of Nanoparticles onto Films.