Comprehensive Biomaterials

Description

c science_2 Editor-in-Chief science_3 Co-Editors science_4 Copyright science_5 Editor-in-Chief Biography science_6 Co-Editor Biographies science_7 Preface science_8 Foreword science_9 Permission Acknowledgments Volume 1 Metallic, Ceramic and Polymeric Biomaterials science Biomaterials science_2 Metals for Use in Medicine Glossary Abbreviations Introduction General Requirements for Long-Term Implantation Key Metallurgy Concepts Chemical Composition and Structure Stainless Steels Cobalt Base Alloys Titanium Base Alloys Other Implantable Metals Mechanical Properties Static Properties Fatigue Processing Effects Metal Processing Overview Process Effect Examples Work hardening and annealing Wrought versus cast alloys Precipitation hardening Surface condition effects Future Developments Summary References science_3 Electrochemical Behavior of Metals in the Biological Milieu Abbreviations Symbols Introduction Metals Currently Used in Medical Devices Titanium Alloys Co-Cr-Mo Alloys Stainless Steel Metallic Biocompatibility Immune Response and Haptens Wound Healing and Biocompatibility The Reduction Half-Cell in Biomaterials Corrosion The Biological Milieu The In Vitro Approximation to the Biological Milieu Basic Electrochemistry Concepts Active Corrosion Theory: Oxidation and Reduction Passivating Metal Surface Behavior Polarization Testing Linear polarization and Rp Cyclic and anodic polarization testing Passive Oxide Films and Semiconducting Electrochemistry Introduction to Passive Oxide Films High Electric Field Oxide Growth Redox Electrochemistry at Oxide-Solution and Oxide-Metal Interfaces Oxide Semiconductor Theory for Thin Oxide Films Between Metals and Solutions Electrical Double Layer Electrochemical Impedance Spectroscopy (EIS) of Metallic Biomaterials The Methods of EIS Time-Based Methods Impedance Behavior of Ti, CoCr, and 316L SS: Effects of Solution, Voltage, and Time Mechanically Assisted Corrosion Modeling the Electrochemical Response to Scratching The Consequences of Mechanically Assisted Corrosion In Vivo Effects of Prior Electrochemical History Oxide Film Structure and Formation Effects of Solution Redox System Biological Consequences: Oxidation and Reduction Summary Appendix: Derivation of Mott-Schottky Equation Acknowledgment References science_4 Shape Memory Alloys for Use in Medicine Glossary Abbreviations Introduction Fundamentals of Shape Memory Systems Practical SMAs Manufacturing, Processing, and Performance of Nitinol Melting Methods and Compositional Effects Production of Semifinished Wrought Products Heat Treatment to Control Performance Characterization Methods and Some Basic Material Properties Transformation temperatures Tensile behavior Minimally Invasive Device Applications for Nitinol Cardiovascular Stents Deployment considerations Manufacturing methods Cardiovascular stents: clinical examples Other Cardiovascular Devices Nonvascular Stents Orthodontic Applications for Nitinol Orthopedic Applications for Nitinol Clinical Imaging of Nitinol Medical Devices Long-Term Durability and Biocompatibility of Nitinol Fatigue Behavior of Nitinol Corrosion Behavior of Nitinol Biocompatibility Aspects of Nitinol Summary and Future Directions References Relevant Websites science_5 Alumina Glossary Abbreviations Introduction Properties of Alumina Physical Properties Mechanical Properties Stability in Wet Environment Wear Behavior of Alumina Simulator tests on alumina-on-PE bearings Simulator tests on alumina-on-alumina bearings Microseparation tests on alumina-on-alumina bearings Biocompatibility In vitro tests In vivo tests Carcinogenecity Reaction to Ceramic Wear Debris Clinical Application of Alumina Ceramics Technology of Alumina for THR Bearings Design of Ceramic THR Bearings Clinical Results Complications Failures in THR bearings Noises in THR bearings Tips and Tricks in Alumina Bearings Revision Strategies Alumina in Knee Replacements Alumina in Other Medical Devices References science_6 Zirconia as a Biomaterial Abbreviations Introduction The Discovery of Phase Transformation in the 1970s: A Revolution in the Ceramic Field The Logical Development as a Structural Bioceramic Phase Transformation and Aging: The Two Sides of Zirconia Crystallography and Phase Transformation of Zirconia Crystallography and Phases Stability Stress-Induced Phase Transformation and Toughening Surface Transformation in the Presence of Water and LTD Different Types of Zirconia and Zirconia-Based Composites Alloy Additives for Zirconia Partially Stabilized Zirconia Ceramics Tetragonal Zirconia Polycrystals Zirconia-Dispersed Ceramics The Use of Zirconia as a Biomaterial: Current State of the Art The Use of Zirconia in Orthopedics: From Yttria-Doped Zirconia to Zirconia-Toughened Alumina The Use of Zirconia in the Dental Field: From Dental Restoration to Implants Future Directions Tough, Strong, and Stable Zirconia Ceramics and Composites: The Necessary Challenge Conclusion Further Reading References science_7 Carbon and Diamond Glossary Abbreviations Introduction Pyrolytic Carbon Introduction Production of Pyrolytic Carbon Fluidized-bed production of pyrolytic carbon Tumbling and stationary bed production of pyrolytic carbon Mechanical Properties of Pyrolytic Carbon Biological Properties and Biomedical Applications of Pyrolytic Carbon Cardiovascular applications of pyrolytic carbon Orthopedic applications of pyrolytic carbon Shortcomings of pyrolytic carbon Diamond-Like Carbon Introduction to DLC Production and Characterization of DLC Raman spectroscopic characterization of DLC Nuclear magnetic resonance and electron energy loss spectroscopy of DLC Properties of DLC Electronic properties of DLC Mechanical properties of DLC Applications and Biological Properties of DLC Orthopedic applications of DLC Cardiovascular applications of DLC Additional applications of DLC Microcrystalline, Nanocrystalline, and Ultrananocrystalline Diamond Introduction to MCD, NCD, and UNCD Production of MCD, NCD, and UNCD CVD and film growth Hot-filament CVD of diamond films Microwave PECVD of diamond films Additional diamond film production methods Mechanical and Biological Properties of MCD, NCD, and UNCD Biomedical Applications of MCD, NCD, and UNCD Biosensor applications Orthopedic applications Further biomedical applications Summary of Carbon and Diamond References science_8 Wear-Resistant Ceramic Films and Coatings Abbreviations Introduction State of the Art - Processing, Microstructure, Biocompatibility, and Mechanical Properties of Ceramic Coatings... Surface Modification Processes Ion implantation Physical vapor deposition Diffusion surface modification Specific Wear-Resistant Surface Modification Processes Oxidized zirconium Titanium nitride (TiN) coatings PVD TiN coatings Diffusional TiN coatings Duplex TiN coatings Diamond-like carbon coatings Multicomponent hard coatings Simulation and Testing of Wear-Resistant Surface Modifications Durability comparisons Wear simulation tests Oxidized zirconium Titanium nitride coating DLC coating DLC-coated metal against UHMWPE DLC coating in hard-on-hard bearings Chromium nitride based coatings In Vivo Performance of Wear-Resistant Ceramic Coatings Animal studies Clinical performance Future Trends References science_9 Bioactive Ceramics Glossary Abbreviations Bioactivity Bone Formation at the Interface with Bioactive Materials Testing Bioactivity In Vitro Methods of Analysis of the Dissolution-Precipitation Reaction Bioactive Glasses Composition of Bioactive Glasses Structure of Bioactive Glass Description of In Vitro Bioactivity Ion exchange and dissolution-precipitation reaction Protein adsorption Bone cell interaction with bioactive glass in vitro Effect of Preparation Methods of Glass on Its Bioactivity Melting method Sol-gel method Bioactive Glass Ceramics Calcium Phosphate Ceramics Composition of Hydroxyapatite Structure of Hydroxyapatite Calcium Deficient Hydroxyapatite Preparation of Hydroxyapatite Composition and Structure of beta-TCP Synthesis of beta-TCP Effect of Composition, Dissolution, Protein Adsorption, and HA Crystal Size on Bioactivity Apatite Formation and Bone Bioactivity of beta-TCP Silica-Calcium Phosphate Nanocomposite Composition Crystalline Structure Structure and Bioactivity Relationship Effect of structure and composition on protein adsorption Effect of structure and composition on bone cell function and tissue formation Silica-Xerogel Conclusion References science_10 Bioactive Glass-Ceramics Abbreviations Symbols AW Glass-Ceramic Apatite-Mica Glass-Ceramics Apatite-Mullite Glass-Ceramics References science_11 Bioactive Ceramics: Physical Chemistry Glossary Abbreviations Introduction Calcium Orthophosphates Used as Biomaterials: Composition, Occurrence, and Brief Synthesis Description... Calcium Phosphates Obtained by Wet Synthesis Methods Monocalcium phosphates Dicalcium phosphates Tricalcium phosphate, whitlockite, and amorphous tricalcium phosphate Octacalcium phosphate Calcium Phosphate Obtained by Dry Synthesis Methods Crystalline tricalcium phosphates: α- and beta-TCP Tetracalcium phosphate Apatites Well-crystallized apatites Nanocrystalline apatites Synthesis and formation of apatites Wet preparations Dry preparation Other Phosphate Compounds Characterization Methods of Calcium Phosphates Chemical Analysis Major ions Calcium Phosphorus Carbonate Hydroxide ions Minor and trace elements Meaning of the Ca/P ratio Diffraction Methods Electron Microscopy Techniques Vibrational Spectroscopies Solid-State Nuclear Magnetic Resonance Properties of Calcium Phosphates Thermal Properties of Calcium Phosphates Reversible decomposition of stoichiometric apatites Irreversible decomposition of nonstoichiometric apatites Solubility Hydrolysis and Aqueous Conversion Surface Charge and Surface Energy Surface charge Interfacial energy Chemical Alterations of the Surface Ion exchange Adsorption Nucleation Properties Biological Response and Physical-Chemical Characteristics Active and Passive Biomaterials with Regard to Ca-P Nucleation Simulated Body Fluid Testing Biodegradation Examples of Applications and Processing Porous Ceramics Coatings, Example of HA-Plasma Spraying Cements Examples of Composite Materials with Collagen Other Bioactive Ceramic Materials Oxide- and Hydroxide-Based Bioactive Ceramics CaCO3-Based Bioactive Ceramics CaSO4-Based Bioactive Ceramics Conclusion and Future Perspectives References Relevant Websites science_12 Calcium Phosphate Coatings Glossary Introduction Calcium Phosphates Titanium Implants Plasma Spraying of CaP Coatings Electrochemical Deposition of CaP Coatings Biomimetic CaP Coatings Conclusion and Perspectives References science_13 Bioactive Layer Formation on Metals and Polymers Abbreviations Introduction Bioactive Layers Bioactive Layers on Metals Bioactive layers on titanium metal and its alloys Sodium titanate layer Calcium titanate layer Titanium oxide layer Bioactive layers on Zr metal Bioactive layers on Nb metal Bioactive layers on Ta metal Bioactive Layers on Organic Polymers Future Perspectives Additional Reading References science_14 Bioactivity: Mechanisms Abbreviations Introduction Mechanisms of Bioactive Behavior Surface Transformation and Protein Adsorption Events of Bioactive Ceramics and Glasses The Effect of Bioactive Ceramics on the Expression of the Osteoblastic Phenotype In Vitro Solution-Mediated Effects of Bioactive Behavior Intracellular Signaling Events Regulating the Stimulatory Effect of Bioactive Ceramics on Cell Function... Correlation of In Vitro and In Vivo Events: The Effect of Bioactive Ceramics on the Osteoblastic Phenotype In Vivo Mechanisms of Biodegradation of Bioactive Ceramics Summary Acknowledgment References science_15 Calcium Phosphates for Cell Transfection Abbreviations Introduction Applications of Bioceramic Cell Transfection The Role of Bioceramic Characteristics for their Applications Bioactivity Degradability Physicochemical Properties Traditional Use of Calcium Phosphate for Cell Transfection Hydroxylapatite Ceramics for Cell Transfection Physicochemistry Transfection of Isolated Cells Transfection of Tissue Culture In Vivo Transfection Perspectives and Material Evolution References science_16 Bioactive Ceramics: Cements Glossary Abbreviations Introduction Bioactive Cement History of Bioactive Cement Advantages of Bioactive Cement Drawbacks of Bioactive Cement Calcium Sulfate History of Calcium Sulfate Setting Reaction of Calcium Sulfate Tissue Response to Calcium Sulfate Clinical Application of Calcium Sulfate Portland Cement and MTA History of Portland Cement and MTA Composition of Portland Cement and MTA Setting Reaction of Portland Cement and MTA Tissue Response to Portland Cement and MTA Apatite Cement Setting Reaction of TTCP-DCPA Type Apatite Cement Fast-Setting Apatite Cement Antiwashout Apatite Cement Injectability of Apatite Cement Mechanical Strength of Apatite Cement Porous Apatite Cement Premixed Apatite Cement Brushite Cement Setting Reaction of Brushite Cement Effect of Additive on Brushite Cement Tissue Response to Brushite Cement Future Direction References science_17 Phosphate-Based Glasses Abbreviations Phosphate Glasses: Physical Properties and Processing Introduction Glass Synthesis Melt-derived glasses Sol-gel derived methods Phosphate Glass Structure and Q Speciation Ternary Glass Systems Phosphate Glass Degradation: General Concepts Ternary glass degradation Phosphate glass dopants: Control of dissolution rate Phosphate glass dopants: Additives for antibacterial use Processing of Phosphate Glass Fibers Biological Properties of Phosphate Glasses In Vitro Biological Properties Introduction In vitro properties of ternary glass systems In vitro properties of quaternary glass systems Phosphate glass fibers In Vivo Biological Properties Introduction Phosphate glasses as bone substitutes In vivo response to phosphate glasses Human clinical trials on phosphate glasses Therapeutic Actions of Phosphate Glasses Introduction Therapeutic Phosphate Glasses Other Potential Therapeutic Phosphate Glasses References science_18 Calcium Phosphate Ceramics with Inorganic Additives Glossary Abbreviations Introduction Bone Current Methods in Bone Regeneration Natural Bone Grafts Synthetic Bone Graft Substitutes Calcium phosphate ceramics Tissue Engineering Improvement of Synthetic Bone Graft Substitutes Trace Elements in Bone Metabolism and Processes Related to Bone Formation Zinc Copper Strontium Fluoride Carbonate Inorganic Additives in Calcium Phosphate Ceramics Methods of Preparation Effect of Inorganic Additives on Ceramic Properties Biological Performance of Ceramics Containing Inorganic Additives Future Perspectives References science_19 Synthetic Bone Grafts: Clinical Use Abbreviations Introduction A Brief History of Bone Grafts Synthetic Bone Graft Substitutes Calcium Sulfate (Plaster of Paris) (Table1) Calcium Phosphate Ceramics (Table1) Calcium Phosphate Cements Bioactive Glasses and Ceramics Glass Ionomer Cements Biomimetic Nanocomposites and Nanopolymers Conclusion References science_20 Polymer Fundamentals: Polymer Synthesis Glossary Introduction to Polymer Science Classification of Polymers Polymer classification according to: Polymerization Systems Polycondensation Characteristics of Condensation Polymerization Kinetics of Linear Polycondensation Molecular weight control in linear polycondensation Nonlinear Polycondensation and Its Kinetics Prediction of the gel point Mechanisms of Polycondensation Carbonyl addition-elimination mechanism Other mechanisms Typical Condensation Polymers and Their Biomedical Applications Addition Polymerization Free Radical Polymerization Initiation Propagation Termination Kinetics of radical polymerization Degree of polymerization Thermodynamics of polymerization Ionic Polymerization Cationic polymerization Anionic polymerization Coordination Polymerization Typical Addition Polymers and Their Biomedical Applications Comparison of Addition and Condensation Polymerization New Polymerization Mechanisms Atom transfer radical polymerization Nitroxide-mediated polymerization Reversible addition-fragmentation chain transfer polymerization Polymer Reactions Copolymerization Types of copolymerization Effects of copolymerization on properties Kinetics of copolymerization Kinetics of addition copolymerization Kinetics of condensation copolymerization: Cross-Linking Reactions Effect of cross-linking on properties Cross-linking of biological polymers Cross-linking of proteins Cross-linking of polysaccharides Cross-linking agents Conclusion References science_21 Structural Biomedical Polymers (Nondegradable) Glossary Historical Overview Classifications of Medical Polymers and Their Applications Polyethylene Acrylates Fluorocarbon Polymers Polypropylene Polyester Polyamide Polyurethane Polyetheretherketone Silicone Designing Structural Implants with Polymers Summary References science_22 Degradable Polymers Glossary Abbreviation Introduction Overview of PLGA Copolymers PLGA History and Uses Common Manufacturing Techniques Parameters Affecting Degradation Rate of PLGA Copolymer Ratio Molecular Weight Crystallinity and Glass Transition Temperature Heterogeneous Degradation Degradation and Length Scale Environmental Factors Affecting Degradation Biocompatibility of PLGA In Vivo Biocompatibility of Implants In Vivo Biocompatibility of Microspheres In Vivo Biocompatibility of Nanoparticles Bioavailability: Damage to Encapsulated Payload Applications of PLGA Across Length Scales Nanoscale Particles Drug delivery Gene delivery Nanoscale Fibers Microscale Particles Vaccines Contrast agent for ultrasound Tissue engineering Macroscale Hydrogel Macroscale Foams Rationale for Development of PPEs Structure-Function Relationships of PPEs Material Properties of PPE Films Degradation Structure-Degradation and Length Scale-Degradation Relationship Toxicity and Biocompatibility of PPEs Design of PPE Drug Carriers Amphiphilic PPE Copolymers as Drug Carriers Drug-Loading Index Effect of Molecular Structure on Critical Micelle Concentration Drug Release Kinetics Design of Thermoresponsive PPEs Molecular Structures of Thermoresponsive PPEs Effects of Solution Properties on Thermal Transition Thermoresponsive PPEs Conjugated to PEG, Gold Nanoparticles, and Enzyme-Cleavable Side Chains Design of PPE and PPA Gene Carriers Molecular Structures of PPE and PPAs Gene Carriers Effect of Polymer Backbone on Gene Delivery Applications PPE/DNA Gene Delivery System PPA-DNA Gene Delivery System: DNA Compaction Capacity of PPAs Effect of N/P Ratio and Cell Culture Conditions on Transfection Efficiency of PPA-DNA Particles Effect of Charged Groups on Transfection Efficiency of PPA-DNA Particles Effect of PPA Side-Chain Structure on Transfection Efficiency Combinatorial Approach Nanoparticle Formulated with PPAs Bearing Different Charge Groups PPA with Imidazole Moiety: Improving Buffering Capacity Effect of on Transfection Efficiency by Ligand-Modified and PEG-Modified PPA Conclusion References science_23 Polymer Films Using LbL Self-Assembly Abbreviations Symbols Introduction: Strategies for Surface Modification with Polymers Fundamentals of Multilayer Formation: LbL Thin Films Electrostatic Self-Assembly of Polymers from Aqueous Solutions Equilibrium and dynamics in PEMs: lessons from PECs Internal structure of electrostatically assembled multilayers Hydrogen-Bonded Self-Assembly of Polymers from Aqueous Solutions Assembly, internal structure, and properties of HB films Effect of polymer solution pH Ionic strength of polymer solutions Temperature of polymer solutions Concentration of polymer solutions Temperature-controlled HB release films LbL-Derived Hydrogels Hydrogels derived from electrostatically assembled multilayers Hydrogels derived from HB multilayers LbL-derived hydrogels via click chemistry Mechanical properties of the LbL-derived hydrogel films Applications of LbL hydrogels to controlled release of bioactive molecules Nanoparticle-containing layered hydrogel films Conclusions References science_24 Polyurethanes and Silicone Polyurethane Copolymers Abbreviations Introduction The Polyurethanes and Polyurethane-Ureas World's Largest Class of Polymers Chemistry and synthetic methods The urethane and urea bonds Commercially important PUs and PUUs Range of Chemical Compositions and Structure Possibilities Lab and Commercial Synthetic Methods Thermoplastic pellets for extrusion and molding Solution synthesis for coating and dipping 100% solids curable prepolymer systems for potting and encapsulation Water-borne dispersions for coatings Utility of PUs and PUUs as Biomaterials Biostable PUs and PUUs Structure and composition: soft-segment chemistry Importance of block and segmented PUs in long-term implants Composition of Important biostable PU and PUUs Chain Extenders Diols Diamines Soft Segments Polyester Adipate esters Lactones Polyethers Other polyalkylene oxides (also known as polyethers) Aliphatic polycarbonates Potential importance of purity/lack of ether contaminants General Properties of Polymers with a Single Soft Segment Chemistry Effect of alkylene chain length Mixed Soft Segments Hydrophobic and Hydrophilic Polyethers Silicone and Polyether and Silicone and Polycarbonate Silicone and Aliphatic Polycarbonate Polydimethylsiloxane (silicone) History of silicone-urethane development Benefits of silicone modification of PU and PUU Improvements in biocompatibility Improved processing of softer elastomers Additives Effect on surface chemistry and biological interactions Composition of Some Bioresorbable Polyurethanes Comparison to Biostable Analogues Degradable soft segments Degradable hard segments Basic Structure-Property Relationships in Block and Segmented PUs and PUUs Effect of Hard-Segment Chemistry and Content Importance of hydrogen bonding Effect of soft-segment chemistry and content Single soft segment Mixed soft segments Effect of end groups on surface chemistry Optimizing polyurethanes for specific biomedical applications Satisfying bulk and surface property requirements Fabrication of Medical Device Components from PUs and PUUs Solution Processing: Dipping, Spraying, Solvent Bonding, and Web Coating Thermoplastic Processing Other Fabrication Methods Sterilization of Segmented and Block Copolymer PUs and PUUs Ethylene Oxide Radiation Gamma irradiation Electron beam Autoclaving Other Methods The Issue of MDA Formation in Aromatic Polyurethanes Extreme Conditions Required to Produce MDA The Need for Aromatic Hard Segments in Biostable PUs and PUUs History of the Issue The Epping Bakery Incident Future of Biomedical Polyurethanes and Silicone Polyurethanes References science_25 Shape-Memory Polymers Glossary Abbreviations Fundamental Principles of Shape-Memory Polymers and of the Quantification of Shape-Memory Properties... Synthesis and Properties of Selected Examples of SMP Intended for Biomedical Applications Multifunctional SMPs by Integrating Hydrolytic Degradability or Controlled Drug Release Capability Biomedical Applications of SMPs References science_26 Electrospinning and Polymer Nanofibers: Process Fundamentals Glossary Abbreviations Symbols Introduction Process Description Mechanics: Electrostatics and Hydrodynamics The Leaky Dielectric Model Governing Equations and Major Results Electrospinning Zones The conical meniscus The thinning jet The whipping jet Discussion on Current Carried by Electrospinning Jet Products of Electrospinning Electrospun Fibers: Diameter and Morphology Properties of the Electrospun Mat Summary and Conclusion References science_27 Fluorinated Biomaterials Glossary Abbreviations Introduction Fluorinated Polymer Chemical and Physical Properties Fluoropolymer Properties Derived from Chemistry, Molecular Structure, and Bonding Perfluorinated Surfaces Fluoropolymers Polytetrafluoroethylene ePTFE (Gore-Tex) Fluorinated Ethylene Propylene Other Fluoropolymers Fluoropolymer Processing Fluorinated Coatings35 Biomedical Applications of Fluorinated Biomaterials PTFE (Teflon) and ePTFE (Gore-Tex) Vascular Implants ePTFE and Teflon Tissue Meshes Arteteriovenous ePTFE Grafts for Dialysis Access Multilumen Catheters Guiding Catheters PTFE Introducer Perfluorocarbon Liquids, Surfactants, and Emulsions as Oxygen-Carrying Blood Substitutes Other Fluorinated Material Biomedical Applications Fluorinated (meth)acrylates and (meth)acrylated perfluoroalkylated silicones as cross-linked polymer cores for s Fluorinated coatings as antifouling coatings for IOLs PTFE paste injectable bulking agent Ligament replacement Sutures Conclusion and Perspectives Acknowledgment References science_28 Engineering the Biophysical Properties of Basement Membranes into Biomaterials: Fabrication and Effects on Cell Behavior... Glossary Abbreviations Introduction Basement Membrane Biochemical Composition of BMs Cellular Adhesion via Macromolecules of BMs Diseases Associated with BMs Biophysical Cues of BMs: Elastic Modulus Biophysical Cues of BMs: Topography Nanostructure Fabrication Design Parameters Classical Lithography Electron-beam lithography Photolithography Next Generation Lithography Nanoimprint lithography Soft lithography Colloidal lithography Electrospun fibers Molecular self-assembly Phase separation Other Methods Cellular Response to Topographic Cues with Dimensions from Nano- to Micron-Scales Micron Range (>1000nm Widths) Submicron (400-1000nm Widths) Upper BM Range (100-400nm Widths) Lower BM Range (10-100nm Widths) Importance of Depth Overview Acknowledgment References science_29 Electroactive Polymeric Biomaterials Abbreviations Introduction Conjugated Polymer Electrode Coatings Polypyrrole Poly(3,4-ethylenedioxythiophene) PPy and PEDOT Derivatives and Copolymers Melanin Conjugated Polymers on Devices Conjugated Polymers for Living Tissue Interfaces Neural Electrodes for Recording and Stimulating Nerve Regeneration Guidance Channels and Bionic Interfaces Neural Communication Through Ionic Stimulation Implantable Modification of Conjugated Polymers Conjugated Polymer/Hydrogel Composites Conjugated Polymer-Based Drug Delivery Synthesis of Conducting Polymers In Vivo Summary and Future Outlook Acknowledgment References science_30 Superporous Hydrogels for Drug Delivery Systems Abbreviations Introduction Hydrogels in Drug Delivery Superporous Hydrogels SPH Synthesis SPH Properties Swelling Capacity Swelling Rate Mechanical Strength SPH Generations The First SPH Generation The Second SPH Generation The Third SPH Generation Research on SPHs SPH Scale Up SPH Stability SPH Identity SPH Purity SPH Potency SPH Safety SPH Platform Design for Drug Delivery SPH in Drug Delivery and Other Areas Gastric Retention Peroral Intestinal Delivery SPHs as Diet Aid SPHs as Superdisintegrant Other Applications Conclusions References science_31 Dynamic Hydrogels Glossary Abbreviations Introduction Motivation: Utility of Dynamic Hydrogels Historical Context: Development of Dynamic Hydrogels Functional Modes/General Dynamic Mechanisms Hydrogen Bonding and Hydrophobic Interactions Electrostatic Interactions and Donnan Equilibrium Competitive Binding Covalent Bonding and Bond Cleavage Specific Stimuli and Response Mechanisms Physical Stimulus Temperature Electrical, magnetic, and electromagnetic fields Electric field Magnetic field Electromagnetic field Pressure Chemical Stimulus pH Ionic strength Ligand binding and ion-specific interactions Biochemical Stimulus Competitive ligand binding Enzyme catalysis Conformational shifts Biomedical Applications Controlled Release of Soluble Factors Step function release Rate modification Switchable surface Sensing and Detection Mechanical Actuation: Artificial Muscles, Robotics, and Microfluidics Artificial muscles and robotics Microfluidics Future Directions References Volume 2 Biologically Inspired and Biomolecular Materials science Bio-inspired Silica Nanomaterials for Biomedical Applications Abbreviations Introduction Biosilicification Introduction Natural Biomolecules Directing Silicification in Sponges and Diatoms Sponge-derived biomolecules: silicateins Diatom-derived molecules: silaffins and long-chain polyamines Bio-inspired Silica Synthesis Bio-inspired Silica Synthesis for Biomedical Applications Introduction Silica Nanoparticles for Medical Imaging Silica-Based Nanomaterials for Biosensors Silica Nanoparticles for Drug Encapsulation and Delivery Silica-Based Nanomaterials for Implants and Tissue Engineering Perspectives and Challenges Silica Biocompatibility Novel Bio-inspired Silica Synthesis Genetically Engineering Silica Biomaterials Hierarchical Design of Silica-Based Next Generation Implants Conclusion Acknowledgment References science_2 Engineering Viruses For Gene Therapy Glossary Abbreviations Introduction Defining Gene Therapy Prospects and Challenges of Gene Therapy Design Requirements for Therapeutic Gene Vectors Techniques for Evaluating Gene Delivery Vectors Reporter genes Gene expression assays In vitro assays In vivo assays Viral Engineering Viruses as Gene Delivery Vectors Rational Approaches to Vector Design Retargeting Immune evasion Library Approaches to Vector Design Library selection Directed evolution Design of Artificial Viruses Materials for Gene Delivery Functionalization of Synthetic Gene Delivery Vectors Ligands for cell binding and internalization Endosomal escape ligands Ligands for cytosolic trafficking Nuclear entry ligands Conclusions and Future Work Future Directions Engineering control systems for gene expression Integration of gene delivery systems with biomaterials Alternative gene delivery systems Safety Considerations Summary References science_3 Protein-Engineered Biomaterials: Synthesis and Characterization Glossary Abbreviations Introduction Rational Design and Modular Building Blocks Structural Domains Bioinstructive Domains Bioresponsive Domains Synthesis and Purification Recombinant DNA Technology and Protein Synthesis Purification of Recombinant Proteins Column chromatography Batch phase separation Lipopolysaccharide removal Postsynthesis Materials Processing Characterization Molecular Structure Details Protein sequence and composition Molecular mass and purity Protein conformation Domain association Material Bulk Properties Mechanical properties Morphological features Biological Interactions and Immunogenicity Future Directions and Conclusions References science_4 Peptoids: Synthesis, Characterization, and Nanostructures Glossary Abbreviation Introduction Bioinspired Polymers Properties of Peptoids as Useful Biomaterials Synthesis Solid-Phase Synthesis Solution-Phase Synthesis Other Methods for Peptoid Synthesis Peptoid Structure and Characterization Peptoid Secondary Structures: Helices and Turns Noncovalent Local Interactions in Peptoids Cyclic Peptoids Computational Modeling Protein-Like Structures and Functions Peptoid Self-Assembly: Nanostructures Combinatorial Discovery of Peptoid Ligands Synthesis Technologies Automated synthesis Parallel synthesis SPOT synthesis Split/mix synthesis Analytical Methods Separations Characterization Screening Methods Drug Discovery Protein Receptor Ligands Protein-protein interaction inhibitors Receptor ligands Nucleic Acid Binders Antimicrobial Agents Lung Surfactants Peptoid Pharmacology Cellular Delivery/Uptake Vectors Cell-Penetrating Peptoids Lipitoids for Cellular Delivery of Nucleic Acids Biomimetic Materials Collagen Mimicry Antifouling Agents Glycopeptoids Other Applications Enantioselective catalysts Summary and Future Directions References science_5 Self-Assembling Biomaterials Abbreviations Introduction Planar Self-Assembling Systems Self-Assembled Monolayers Functionalized SAMs for Modulating Cell Attachment Patterning and SAMs Responsive Elements and Dynamic SAMs 3D Self-Assembling Systems Self-Assembling Peptides Coiled Coils Biomaterials from Coiled Coils Self-Assembling Peptides Based on beta-Sheet Fibrils Self-Assembling Peptides Based on Collagens Self-Assembling Peptide Amphiphiles Self-Assembling Peptides with Aromatic Groups beta-Hairpins Proteins Modulating the Mechanics of Self-Assembling Systems Advantages Provided by Self-Assembled Systems for Biomaterials Applications Immune and Inflammatory Responses to Self-Assembling Materials In vivo Applications of Self-Assembled Biomaterials Concluding Remarks References science_6 Phages as Tools for Functional Nanomaterials Development Glossary Abbreviations Introduction Introduction of Bacteriophage Structure of M13 Phage Directed Evolution of Phage Phages for Inorganic-Organic Hybrid Materials Self-Assembly of Inorganic Materials using Phage Phage for Energy Materials Phage for Energy Storage Materials Phage for Energy Producing Materials Phage for Sensing Materials Phage-Based Molecular Recognition Phage for a Sensing Platform Micro- and Nanomechanical Sensing Electrochemical Sensing Optical Sensing Phage for Biomedical Application Phage Therapy Phage for Drug and Gene Delivery Phage for Tissue-Engineering Materials Summary and Future Perspectives References science_7 Extracellular Matrix: Inspired Biomaterials Glossary Abbreviations Introduction Overview of ECM Structure and Function Types of ECM Mimicry Mimicking ECM Functions by Using ECM Components Full/direct copy Case study: hydroxyapatite/collagen nanocomposite based material for bone regeneration Case study: use of ECM scaffolds to repair ligaments Partial copy Case study: multiple ligand-integrin interactions alter intracellular signaling Case study: enhancement of chrondrogenic differentiation by MMP-13 degradable hydrogels Mimicking ECM Function Through ECM Architecture and Topography Hierarchical microstructure and porosity Case study: anisotropic honeycomb structure for ventricular myocardium repair Topographical features and patterning Case study: electrospun nanofibers for repair of peripheral nerves Mimicking ECM Protein Design and Assembly Future Directions References science_8 Artificial Extracellular Matrices to Functionalize Biomaterial Surfaces Abbreviations Introduction Components to Be Used for aECM Collagens Noncollagenous Glycoproteins Elastin Fibronectin Laminin Vitronectin Tenascin, osteopontin, and thrombospondin Proteoglycans Small leucine-rich proteoglycans HyA-binding PGs (hyalectans) Non-HyA-binding PGs Glycosaminoglycans Hyaluronan Heparin/HS Chondroitin sulfate, dermatan sulfate, and keratan sulfate Biological Interaction Profiles of aECM and Their Components Direct Cell-surface receptors Collagen Glycoproteins Fibronectin Laminin Vitronectin Tenascin, osteopontin, and thrombospondin Proteoglycans Glycosaminoglycans Indirect Collagens and glycoproteins Proteoglycans Glycosaminoglycans Mechanism of GAG-protein binding Physiological significance Inflammation and injury Preparation and Structure of aECM Heterotypic Fibrils Collagen Fibrils with Glycoproteins Collagen Fibrils with PGs Collagen Fibrils with Modified Proteins and/or Peptides Collagen Fibrils with GAGs Biochemical Characterization of aECM Glycoproteins and PGs Glycosaminoglycans Growth Factor Interactions Immobilization of aECM Cell Biological Effects of aECM Collagens Glycoproteins and PGs Glycosaminoglycans Results from Animal Experiments Collagens Glycoproteins and PGs Glycosaminoglycans Conclusions and Outlook References science_9 Materials as Artificial Stem Cell Microenvironments Glossary Abbreviations Introduction The Adult Stem Cell and Its Niche Naturally Derived ECM Components for In Vitro Stem Cell Manipulation Engineered Substrates as Artificial Stem Cell Niches Control of Stem Cell Fate by Biomolecule-Functionalized Substrates Instructing Stem Cells via Engineered Substrates with Tailor-Made Biophysical Properties Instructing Stem Cells via Engineered Substrates with Controlled Spatial Properties High-Throughput Approaches to Identify Complex Artificial Niche Substrates Topographically Patterned Substrates as Versatile Stem Cell Microenvironments Biomaterials Approaches to Emulate Stem Cell Niches in 3D Building a Molecular Toolbox for 3D Artificial Niches Toward High-Throughput Screening of 3D Microenvironments 3D-Micropatterning of Artificial Stem Cell Niches and Cells Toward Constructing Tissue Models Conclusions References science_10 Bone as a Material Glossary Abbreviations Introduction Bone Composition Collagen Mineral Noncollagenous Proteins Bone Cells Mesenchymal stem cells and osteoprogenitors Osteoblasts and bone-lining cells Osteocytes Osteoclasts Bone Formation Endochondral Ossification Intramembranous Ossification Bone Structure and Hierarchical Organization Bone Tissue Structure and Organization Organ Level Bone Mechanical Behavior Structural Mechanical Behavior of Trabecular Bone Tissue Mechanical Behavior of Bone Fracture Behavior Bone as a Dynamic Adaptive Material Bone Modeling Bone Remodeling Fracture Healing Mechanosensation Bone as a Material During Disease and Drug Treatment Osteoporosis Bone cell biology during osteoporosis Mechanical behavior and structure during osteoporosis Approaches for treatment of osteoporosis Conclusion References science_11 Polymers of Biological Origin Introduction Natural-Based Polymeric Systems Materials Inspired from the ECM Collagen Fibronectin Glycosaminoglycans Fibrin Other Peptide-Based Systems Hydrogels enabling enzymatically mediated cell migration Self-assembling materials Other protein-derived biomaterials Polysaccharides Plant polysaccharides Exudate gums Algal polysaccharides Animal polysaccharides Microbial polysaccharides Natural-Derived Polyesters Processing of TE Scaffolds Microspheres and Microparticles and Their Aggregation Fiber Meshes and Fiber Bonding Rapid Prototyping Cell Encapsulation in Injectable Biodegradable Hydrogels for TE Applications General Principles Selected Examples Final Remarks References science_12 Silk Biomaterials Glossary Overview Silk Film Biomaterials Water Annealed and Slow Drying Silk Films Electric Field Aligned Silk Films Ultrathin Silk Films Silk Sponge Scaffold Biomaterials Silk Nanofiber Biomaterials Silk Nanofibers from Organic Solvent Silk Nanofibers from Aqueous Solvent Silk Nanofiber Composites Silk Hydrogel Biomaterials Natural Silk Hydrogel Ultrasound-Induced Silk Hydrogel Semi-interpenetrating Silk Hydrogels Injectable Silk Hydrogels Silk Microsphere and Nanoparticle Biomaterials Spray-Drying Silk Microspheres Silk Particles from Lipid-Aqueous Separation Silk Particles from Rapid Laminar Jet Silk Particles from Polymer Phase Separation Silk Particles from Organic-Aqueous Phase Separation Silk Particles from pH Variation Silk-Coated Polymer Particles Silk Optical Biomaterials Silk Nano- and Micropatterned Optical Materials Silk Optical Waveguides Color-Controllable Silk Materials Silk-Based Cornea Tissue Engineering Other Silk Materials Silk Microfluidic Devices Secondary Structure Micropatterned Silk Materials Direct-Write Silk Scaffolds Chemically Modified Silk Materials Conclusions Acknowledgment References science_13 Chitosan Glossary Abbreviations Sources, Analysis, and Properties Chemical Structure Solution Properties Chitosan Preparation: Chitin Isolation and N-deacetylation Chitosan Characterization Degree of acetylation Molecular weight General Aspects of Biological Behavior Biocompatibility Cytocompatibility Bacteriostatic and fungostatic properties Enzymatic degradation Immunoadjuvancy Hemostatic and blood clotting properties Cell-binding properties Wound-healing properties Bone-healing properties Chitosan Functionalization Processing Films and Porous Scaffolds (Freeze-Drying and Freeze-Gelling) Nanofibers Polyelectrolyte Complexes Micro- and Nanoparticles Cross-linking Biomedical Applications Wound Management Tissue Repair and Regeneration Delivery of Therapeutic Agents Other Applications Future Prospects References Relevant Websites science_14 Hyaluronic Acid Abbreviations Introduction Biological Origin and Primary Structure of Hyaluronic Acid HA Structure of Higher Orders Biophysical Function of HA Influence of HA on Cell Behavior Production of HA Isolation of HA from Cock Combs Bacterial Fermentation with Streptococci Bacterial Fermentation with Recombinant Bacillus subtilis Chemoenzymatic Synthesis Analysis and Industry Standards Qualitative Analysis Quantitative Analysis Absolute Viscosity Pseudoplasticity IV and Molecular Weight Elasticity Purity and Biocompatibility Chemical Modification of HA Rationale for HA Derivatization Monolithic HA Derivatives Carbodiimide-mediated reaction products N-acylureas Carbodiimide-mediated hydrazide chemistry Carbodiimide-mediated aminooxy chemistry Divinylsulfone cross-linking Esterification Hydrophobic esters Autocrosslinked HA Melt-processable esters Physically and chemically cross-linked HA esters Bis-epoxide cross-linked HA and epoxide-modified HA Ionic cross-linking and polyelectrolyte complexes Monolithic photocrosslinked hydrogels Living HA Derivatives Thiol-modified HA Haloacetate-modified HA Methacrylated HA Tyramine-modified HA Alkynylated and azidoalkylated HA Medical Applications of HA Ophthalmic Surgeries Viscosity and lubricity Thickness of coating and easiness of the removal of HA Cohesiveness and dispersiveness Injections for Osteoarthritic Joints Effectiveness of HA injected in the knee Clinical performance of native and chemically cross-linked HA Mechanism of action for exogenous HA in the knee Cosmetic Tissue Augmentation Residence time Elasticity Safety and reversibility Acute and Chronic Wound Healing Acute cutaneous wounds Acute surgical wounds Seprafilm Autocrosslinked HA products Ionically cross-linked HA Thiol-modified HA Chronic wounds Esterified HA Thiol-modified GAGs and growth factors Selected Uses in Tissue Engineering and 3D Cell Culture 3D cell culture Modular sECMs170 Human embryonic stem cells (hESCs) Cartilage and bone repair models Osteochondral defect repair with esterified HA Defect repair with living HA Future Perspectives and Conclusions The Future of HA Science Concluding Remarks Acknowledgment References science_15 Collagen: Materials Analysis and Implant Uses Glossary Abbreviations Origins of Collagen and Role in Animal Physiology Collagen: A Component of the Extracellular Matrix General Characteristics of Collagen The Collagen Family: Types and Forms The Biochemical Fingerprint of Collagen Primary Structure Secondary to Quaternary Structure of Collagen Supramolecular Assembly of Collagen Natural Cross-Links of Collagen Aggregates Classical collagen cross-links Sugar-based collagen cross-links Other enzymatic cross-links Sources of Collagen Collagen: Purification and Analysis Biomedical Applications of Collagen Outlook and Future for Collagen Materials Acknowledgment References science_16 Collagen-GAG Materials Abbreviations Symbols Introduction Collagen Glycosaminoglycans Collagen-GAG Material Development Antigenicity and Immunogenicity of Collagen-GAG Materials Fabrication of Collagen-GAG Materials CG Scaffold Fabrication: Lyophilization Modifications to CG Scaffold During Fabrication Relative density Pore size and shape Crosslinking CGCaP Scaffold Fabrication Multicompartment CG Scaffold Fabrication CG Hydrogels CG Membranes Characterization of Collagen-GAG Materials Microstructure: Experimental Measurement and Modeling Permeability: Experimental Measurement and Modeling Mechanical Properties: Experimental Measurement and Modeling CG Scaffold Degradation Kinetics and Byproducts In Vitro Applications Cell Attachment and Viability Cell Contraction Cell Motility Growth Factor and Gene Delivery Modifying Gene Expression Mechanical Stimulation Stem Cell Differentiation In Vivo Applications Dermal Regeneration Applications Peripheral Nerve Regeneration Applications Conjunctiva and Corneal Regeneration Applications Cartilage and Fibrocartilage Disk Tissue Engineering Applications Bone, Osteochondral Regeneration Applications Brain Tissue Engineering Applications Lung Tissue Engineering Applications Conclusions References science_17 Fibrin Glossary Abbreviations Historical Perspective Composition, Structure, and Properties Composition and Polymerization Structure and Mechanical Properties Degradation Process: Fibrinolytic Properties Inherent Biological Properties Fibrin Use as a Delivery System Cell Delivery System Drug and Growth Factor Delivery System Drug delivery system Growth factor delivery system Gene Delivery System Viral delivery Nonviral delivery Fibrin in Tissue Engineering Applications Vascular Tissue Engineering Vascular grafts Engineered cardiovascular tissues Bone Tissue Engineering Cartilage Tissue Engineering Nervous Tissue Engineering Other Tissue Engineering Applications Skin Liver Skeletal muscles Tendons and ligaments Fibrin in Clinical Practice Commercially Available Fibrin Sealants Examples of Fibrin Uses in Clinical Practice Cardiovascular and thoracic surgeries Applications as a hemostatic agent in cardiac surgeries Applications in synthetic vascular grafts Applications in cardio patches Plastic and reconstructive surgeries Graft adherence Hemostasis Face-lift surgeries and seroma prevention Other clinical applications Gastrointestinal Neurosurgery Ophthalmology Urology Conclusion References Relevant Websites science_18 Elastin Biopolymers Abbreviations Recombinant Human Tropoelastin-Based Constructs Introduction Synthetic Human Elastin Hydrogels Chemically cross-linked SHE hydrogels Enzymatically cross-linked SHE hydrogels SHE hydrogels formed under alkaline conditions in the absence of a cross-linker Electrospun rhTE Fibers Electrospun rhTE and vascular tissue engineering Electrospun rhTE and skin tissue engineering Functionalized Surfaces The Elastin-Like Recombinamers Introduction The Extraordinary Properties of ELRs Genetic Engineering of ELRs The Stimuli-Responsive Behavior and Self-Assembly Properties of ELRs Biomedical and Biotechnological Applications Tissue engineering Functionalized surfaces Fibers Drug delivery ELR-fusion constructions Outlook Animal-Derived Solubilized Elastin Introduction Types of Solubilized Elastin α- and beta-elastin kappa-elastin Enzymatically solubilized elastin Biomaterials Containing Animal-Derived Solubilized Elastin In Vitro Experiments Blends with natural materials Blends with polymers In Vivo Experiments Clinical Applications Future Directions References science_19 Biophysical Analysis of Amyloid Formation Glossary Abbreviations Symbols Introduction Monomer Folding α-Synuclein Structural Heterogeneity Antiparallel Arrangement of α-Synuclein Helices Aggregation Intermediates Aggregation Kinetics Morphology of Aggregation Intermediates Secondary Structure of Aggregation Intermediates Protein Interactions Mature Amyloid Fibrils Structural Polymorphism of Amyloid Fibrils Mechanical Deformation of Fibrils Conclusion Acknowledgment References science_20 Extracellular Matrix as Biomimetic Biomaterial: Biological Matrices for Tissue Regeneration Glossary Abbreviations Extracellular Matrix Materials Applied in TE Synthetic Materials Biological Materials Synthetic biological materials Decellularized biological materials Induction of Graft Vascularization Indirect Revascularization Induction of Angiogenesis In Vitro Biological Vascularized Scaffold Generation Application as In Vitro Test System Application as Transplant Summary and Future Directions References science_21 Decellularized Scaffolds Abbreviations Introduction What is Decellularization Benefits and Challenges of Decellularization Decellularization Methodology Physical Methods Chemical Methods Solvent extraction Alkaline and acid treatments Detergent extraction Nonionic detergents Ionic detergents Cationic detergents Zwitterionic detergents Hypotonic and hypertonic treatment Enzymatic treatment Additional Reagents Additional Processing Important Considerations Characterization of decellularization Host response to decellularized scaffolds Origin of Decellularized Scaffolds and their Applications Small Intestine Dermis Urinary Bladder Vascular and Cardiac Tissue Embryoid Body Matrix Concluding Remarks References science_22 Xenogenic Tissues and Biomaterials for the Skeletal System Glossary Abbreviations Introduction ECM Composition Collagen and Elastin Proteoglycans and Glycosaminoglycans Fibronectin and Laminin Growth Factors Xenogenic Tissues, ECM Biopolymers, or Cells in Tissue Engineering Bone Reconstruction Intervertebral Disc Reconstruction Tendon Reconstruction Limitations Future Perspectives Acknowledgment References science_23 Bacterial Cellulose as Biomaterial Abbreviations Introduction Bacterial Cellulose: Growth Modification of Nanostructure Engineering of Morphology Shaping in 3D Structure Biocompatibility Biomechanics Cell Interactions and Migration Biomedical Applications Future Outlook References Relevant Websites Volume 3 Methods of Analysis science Surface Analysis and Biointerfaces: Vacuum and Ambient In Situ Techniques Glossary Abbreviations Introduction Needs Assessment for Surface Analysis Defining the Surface of Interest Sample Preparation and Handling for Surface Analysis Sample Analysis Strategy Surface Analysis Methods Ambient Analytical Methods Contact Angle and Surface Energy Measurements Ambient Surface Spectroscopy and Optical Waveguide Methods Surface-Sensitive Infrared Spectroscopy Ellipsometry Surface Plasmon Resonance and Other Total Internal Reflection Optical Sensing Tools Scanning Probe Surface Imaging Techniques Surface Analytical Detection Using Shear-Mode and Surface Acoustic Wave Oscillator Devices TSM oscillator QCM with dissipation monitoring Ultrahigh Vacuum Surface Analytical Techniques Electron Spectroscopy for Chemical Analysis Secondary Ion Mass Spectrometry Auger Electron Spectroscopy Next Challenges: Nanomaterial Surfaces Conclusions Acknowledgment References science_2 Atomic Force Microscopy Abbreviations Symbols Introduction Fundamentals of the AFM Principles of AFM Contact Mode Imaging Dynamic Imaging Modes Intermittent-contact imaging Force modulation and phase imaging Force modulation Phase imaging Noncontact imaging modes Force-Distance Measurement and Force Mapping Force-Distance Curve Force Mapping Nanoindentation and Measurement of Near-Surface Nanomechanical Properties of Polymeric Biomaterials Probing Molecular Interaction and Recognition Sites on Biosurfaces Modification of AFM Probes Measuring Adhesion Forces of Protein to Biomaterial Surfaces Molecular Recognition of Proteins in Dual Component Protein Film Measuring the Functional Activity of Adsorbed Proteins Limitations and Perspectives References science_3 Proteomic and Advanced Biochemical Techniques to Study Protein Adsorption Abbreviations Introduction Unbiased Analysis of Adsorbed Proteins by Polyacrylamide Gel Electrophoresis Analysis of Adsorbed Proteins by 2DPAGE Identification of Proteins by Mass Spectrometry Quantification of Protein Amounts by Mass Spectrometry Proteomics to Study Protein Denaturation on Surfaces Challenges of the Proteomics Approach Conclusions References science_4 Developments in High-Resolution CT: Studying Bioregeneration by Hard X-ray Synchrotron-Based Microtomography Glossary Abbreviations Hard X-ray Microimaging Laboratory Approach Synchrotron Light Sources Quantitative Volume Image Analysis Microtomography: Life Sciences, Biomaterials and Bone Research Comparative Animal Study of Bioceramic-Supported Bone Regeneration Surgery and Specimen Retrieval Microtomography and Volume Image Processing Results Bone Regeneration After Sinus Floor Augmentation in Humans Surgery and Biopsy Microtomography and Volume Image Analysis Results Summary science_5 Biomedical Thin Films: Mechanical Properties Abbreviations Introduction Why Surface Engineering? Coating Techniques Plasma Coating of Calcium Phosphates Nanocrystalline Coatings Physical vapor deposition Chemical vapor deposition Sol-gel nanocoating method Diamond-like Carbon Thin Film Mechanical Testing: Methods Instrumented Nanoindentation Adhesion and Wear Test Methods Pull-off testing Scratch testing Pin on disk Microtensile Testing Bending Tests Bulge and Blister Testing Stress Measurements Concluding Remarks Acknowledgment References science_6 Microindentation Abbreviations Introduction Overview of Nanoindentation Technique Measurement of Elastic Modulus and Hardness Instrument Calibration Basic calibration of force and depth measurement systems The determination of the load frame compliance, Cf Indenter tip shape calibration Indentation Stress-Strain Relationship Measurement of Fracture Toughness and Residual Stress Fracture toughness Residual stresses Indentation Creep Other Factors that Influence the Accuracy of the Results Application of Nanoindentation to Biomaterials Elastic Modulus and Hardness of Enamel Stress-strain Relationship of Enamel Creep Behavior of Enamel Nanoindentation of Caries Lesions Summary References science_7 Finite Element Analysis in Bone Research: A Computational Method Relating Structure to Mechanical Function Glossary Abbreviations Introduction The Finite Element Analysis Macroscale: Whole Bone Continuum-Level FE Microstructural FE Femur Continuum FE models muFE models Radius muFE models Vertebra Continuum FE models muFE models Mesoscale: Trabecular Bone Conceptual Cellular Solids Modeling Role of architectural disorder and defects Trabecular thinning versus trabecular loss Towards patient-specific stiffness and strength predictions muFE Modeling Homogeneous versus heterogeneous tissue at the trabecular level Failure properties Structural and mechanical anisotropy The role of structural indices Mechanical behavior of single rods and plates Microscale: Ultrastructural Features Osteocyte Lacunae Canal Network Nanoscale: Mineral and Collagen Mechanics of the Mineral-Collagen Nanocomposite Conclusions and Future Directions References Relevant Websites science_8 The Mechanics of Native and Engineered Cardiac Soft Tissues Glossary Abbreviations Introduction Background Structure-Function Relationships in Cardiovascular Tissues Nonlinearity of Soft Tissues Heart Valve Tissues Heart Valve Tissue Biomechanics Planar Biaxial Tensile Biomechanical Behavior of the Aortic Valve Leaflet Flexural Response of Native Valvular Tissues Micromechanics of Heart Valve Cells Myocardium Constitutive Models of Soft Tissues Introduction Stress and Strain Definitions Phenomenological Hyperelastic Constitutive Models Fung and Coworkers Structural Constitutive Models for Multiphase Soft Tissues Emulating Native Tissue Mechanical Behavior in Engineered Tissues Introduction Electrospun Scaffolds Modeling Scaffold Structure-Function Relationships Acknowledgment References science_9 Fluid Mechanics: Transport and Diffusion Analyses as Applied in Biomaterials Studies Abbreviations Symbols Introduction Transport Phenomena: Diffusive, Convective, and Reactive Transport Mechanisms Analysis of Transport Models in Porous Media Flow Field Evaluation Direct numerical simulations: mathematical formulation Initial and boundary conditions Numerical methods Finite difference method Finite element method Finite volume method Lattice-Boltzmann method Pore-scale geometry description Macroscopic averaged equations Volume averaging technique: mathematical formulation Mathematical formulation Numerical solution procedure Darcy's law model Darcy-Brinkman model Darcy-Brinkman-Forchheimer model Correlations for estimating porous scaffold permeability Direct methods for the estimation of permeabilities Comparison of direct estimations with correlations Mass Transfer Equations Direct numerical simulations Macroscopic averaged equations Cell growth kinetics Cell growth and modification of flow field equations Evaluation of effective diffusivities Conclusion References science_10 Computational Methods Related to Reaction Chemistry Abbreviations Introduction Computational Methods Molecular Dynamics Homology Modeling Free Energy Free-energy perturbation Umbrella sampling Electronic Structure Methods Electronic structure methods in force-field development QM/MM simulations Methods for Determining Reaction Paths Transition path sampling142,143 BOLAS sampling for calculating free energies Effect of Force on Biomolecules Limitations and Caveats Applications Ab Initio Simulations of Material Properties Surfaces with Tailored Functionality Through Self-Assembly Techniques Slow Dynamical Modes in Adhesion, Catalysis, and Force Computational modeling of the attachment function of fibronectin Future Directions Acknowledgment References Relevant Websites science_11 Molecular Simulation Methods to Investigate Protein Adsorption Behavior at the Atomic Level Abbreviations Symbols Introduction Fundamental Aspects of Protein Adsorption Behavior Molecular Simulation Methods and Their Relevance to Protein Adsorption Overview QM Methods Classical Mechanics Methods Overview Empirical force field equations Representation of solvation effects Set up, control, and calculation of properties in a CM simulation MC and MD methods Accelerated sampling methods Application of All-Atom Modeling Methods to Simulate Protein-Surface Interactions Early Efforts Beginning in the Late 1980s Simulations with limited conformational sampling and treatment of solvation effects due to computational limitat Early MD simulations of protein-surface interactions with increased conformational sampling and explicit solvati Early matched experimental and simulation efforts to support force field parameterization for protein-surface in Early MD simulations of protein-surface interactions with minimal constraints Advancements in Protein-Surface Simulations in the First Decade of the Twenty-First Century Protein interactions with surfaces presenting organic functional groups Protein interactions focused on surfaces presenting inorganic functional groups Current Limitations and Directions for Further Development Force Field Transferability for Protein-Surface Interactions Representation of Solvation Effects for Protein-Surface Interactions Phase-Space Sampling for Protein-Surface Interactions Coarse-Grained Molecular Modeling Methods Concluding Remarks Acknowledgment References Relevant Websites science_12 Cell Culture Systems for Studying Biomaterial Interactions with Biological Barriers Abbreviations Introduction Major Epithelial and Endothelial Barriers in Drug Transport Epithelial barriers of the gastrointestinal tract Inhalation barriers: airway epithelium Skin Blood-Brain Barrier Other Routes for Drug Delivery Tissue Targeting The Upper Respiratory Tract: Barrier Functions of the Bronchial Epithelium Introduction Mucociliary Clearance Integrity of the Bronchial Epithelium Cell Culture Models of Bronchial Epithelial Cells Human Primary Cell Bronchial Coculture Models Specific Applications Transport through barriers Ciliary beat frequency Potential and Limitations of the Bronchial Models The Lower Respiratory Tract: Cell Culture Models Mimicking the Biological Barriers of the Distal Lung... The Biological Barriers of the Distal Lung Cell culture models of alveolar epithelial cells Characterization of alveolar epithelial cells Primary Isolated Human Alveolar Type II Epithelial Cells Human Cell Lines with Alveolar Epithelial Cell Characteristics Cell Culture Models of the Alveolar-Capillary Barrier Characterization of Human Pulmonary Capillary Endothelial Cells Primary Alveolar Epithelial Cells and Microvascular Endothelial Cells in Coculture Coculture of NCI H441 with ISO-HAS-1 Specific Applications Transport studies Uptake of micro- and nanoparticles Influence of cytokines on barrier properties Potential and Limitations of Available Cell Culture Models In Vitro Studies with Endothelial Cells from the BBB Introduction Characteristics of the BBB Characterization of Brain Endothelial Cells Primary Isolated Human Brain Endothelial Cells Primary Porcine Brain Endothelial Cells and Pericytes Isolation Characterization In vitro coculture model with PBECs and pericytes Analysis of Novel Biomaterials with Cells from the BBB Conclusion and Future Perspectives Acknowledgment References science_13 Histological Analysis Abbreviations Introduction Preservation of Tissue Resolution Level Storage Fixation Perfusion Fixation Preserving the Immunoreactivity Fixation for Bone Biopsy Samples (1x5mm) up to Bone Slices (8-10mm thickness) with Implants In Situ... Dehydration Infiltration Embedding of Bone Biopsies in Technovit 9100 NEW Resin Cutting the Small Bone Biopsies (see additional information below) Artifacts Undecalcified Versus Decalcified Clarifications of the Intended Purpose Solutions/Chemicals for Decalcification of Bone Tissue Advantages and Disadvantages Artifacts Embedding Techniques Undecalcified Versus Decalcified Embedding Materials Resin Paraffin Tissue Tech, OCT Compounds (Optimal Cutting Temperature) Artifacts Artifacts related to paraffin Artifacts related to frozen sectioning Sectioning Techniques Ground Sections: Cutting and Grinding Technique Add Modum Donath Artifacts Microdissection Staining Methods Staining for Histological Observations Immunohistochemistry In Situ Hybridization Quantification Methods Level of Quantification What and How to Quantify? Methods and Equipment/Software Reference Sections and Reference Quantifier: In-house Standard Rules X-rays Microcomputed Tomography and Synchrotron Radiation-Based muCT Histological Versus Biomechanical Quantification Combination of Techniques for Quantification of Bone Remodeling Confocal laser scanning microscope Gene expression Summary and Future Directions References Recommended Handbooks science_14 Materials to Control and Measure Cell Function Abbreviations Introduction Influence of Surface Features on Cell Function Cell Adhesion Cell Migration/Contact Guidance Cell Proliferation and Differentiation Influence of Surface Features on Bacteria Function Initial Adhesion Biofilm Formation Applications in BioMEMs/Microsystems Fields Cell Culture Control of adhesion, migration, proliferation, and differentiation Cocultures 3D cultures Cell Docking Cell Separation and Enrichment Cell Transfection Contact Guidance/Cell Migration Cell Mechanobiology Use of Cell Properties Conclusions References science_15 Biological Microelectromechanical Systems (BioMEMS) Devices Glossary Abbreviations Introduction Cell Adhesions to the Microenvironment BioMEMS Devices to Measure Traction Forces Membrane Wrinkling Traction Force Microscopy MEMS Adapted Tools Microposts BioMEMS Devices to Apply Forces to Cells Micromanipulation Magnetic Bead Forces Optical Traps/Tweezers Magnetic Microposts Cytoskeletal Force Response Nanoscissors Microfluidic Systems Fluid Shear Stress BioMEMS Reactors Bioreactor Pumping Bioreactor Configuration Interstitial Shear Single Cell Analysis Cell Sorting Organ on Chip Microfluidic Devices Analysis of Mechanotransduction or Morphogenesis Biomarkers Future Directions Acknowledgment References science_16 Immunohistochemistry Abbreviations Introduction to Immunohistochemistry Factors Contributing to Antibody-Antigen Interaction Affinity Avidity Specificity Stability Visualization of Antibody by Enzymatic or Fluorescent Labeling and The Advantages and Disadvantages Enzymatic Labeling and Common Chromogens Fluorescence Labeling and Fluorophores Basic Immunohistochemistry Protocols and Their Advantages and Disadvantages for Biomaterial Science Tissue Preparation Paraffin-embedded tissues Fixation Formalin Paraformaldehyde Ethanol, methanol, and acetone Antigen retrieval Tissue processing Protocol for paraffin embedding Outline placeholder Outline placeholder Specimen orientation Embedding Frozen tissues Protocol for dry ice/isopentane freezing Immunohistochemical Staining Protocols Immunohistochemical (indirect, three-step) staining protocol for formalin-fixed, paraffin-embedded sections Immunohistochemical staining protocol for frozen sections Immunofluorescence protocol for frozen sections (single and double labeling) Counterstaining and Mounting Counterstaining following immunohistochemical staining Mounting following immunohistochemical staining Data Interpretation Detection of Pathobiological Processes and Associated Cellular Events in an Implanted Site Wound-Healing Response Inflammatory phase Neutrophils Macrophages Lymphocytes Proliferative phase Epithelialization Fibroblasts Myofibroblasts Smooth muscle cells Differentiation of fibroblast, myofibroblasts, and smooth muscle cells using immunohistochemistry... Maturation/remodeling phase Collagen Proteolytic enzymes Cytokines Angiogenesis Immune Response Encapsulation Calcification Implant Evaluation Using Immunohistochemical Methods Heart Valve Prostheses Polymer-Based Engineered Tissues Vascular Grafts Intravascular Stents Cardiac Assist Devices and Artificial Hearts References Relevant Websites science_17 Fluorescence Imaging of Cell-Biomaterial Interactions Abbreviations Introduction Principles, Instrumentation, and Methodology for Cell Imaging Epifluorescence Microscopy and Deconvolution Microscopy Confocal Microscopy Multiphoton Microscopy Other Advanced Fluorescence Imaging Techniques Probing Cell-Biomaterial Interactions Introduction to Fluorescence-Based Probes Fluorophore-tagged antibodies Quantum dot-based probes GFP and variants Case Studies of Imaging Cell-Biomaterial Interactions Case study 1: Fluororeporter imaging of cell cytoskeletal remodeling and apoptosis on biomaterials... Case study 2: Multiphoton fluorescence imaging of 3D polymer scaffolds and cellular organization... Case study 3: Confocal microscopy of cell-based fluororeporters for high-content imaging of cell-biomaterial int Case study 4: Combination of high-content and high-throughput fluorescence imaging for cell-biomaterial interact Looking to the Future Acknowledgment References Relevant Websites science_18 Molecular Imaging Glossary Abbreviations Introduction Nanomaterials Quantum Dots Structure and properties Synthesis Biological interaction Applications Cellular imaging In vivo imaging Perspectives and challenges Gold Nanomaterials Structure and properties Synthesis Biological interactions Applications Cellular imaging In vivo imaging Superparamagnetic Nanoparticles Structure and properties Synthesis Biological interactions Applications Cancer imaging Apoptosis imaging Cardiovascular imaging Perspective and challenges Nanovesicles Liposomes Structure and properties Synthesis Applications Optical contrast agents MR-contrast agents CT contrast agents Ultrasound contrast agents Perspective and challenges Polymersomes Structure and properties Synthesis Biological interactions Applications Optical contrast agents MR-contrast agents Polymeric Assemblies Dendrimers Structure and properties Synthesis Biological interactions Applications Optical contrast agents MR-contrast agents CT contrast agents Future Outlook References Relevant Websites science_19 Characterization of Nanoparticles in Biological Environments Abbreviations Introduction Definition of Nanoparticles Interactions of Nanoparticles Characterization of Nanoparticles in or from Solution Scattering Methods Microscopy-Based Methods Field-Flow Fractionation Examples of Nanoparticles in Biological Environments The Fate of Nanoparticles in Living, Biological Environments Influence of the Nano-Bio Interface on Nanomaterial-Mediated Biological Effects Conclusions and Outlook Acknowledgment References science_20 Nanostructured Polymeric Films for Cell Biology Abbreviations Introduction Controlled Protein Adsorption on BCP and Polymer Blend Surfaces Protein Adsorption on Homopolymer Blend Surfaces Protein Adsorption on BCP Thin Film Templates Protein and Cell Binding via Affinity Interactions Templated by Polymer Surfaces Protein Immobilization and Patterning on Polymer Affinity Templates BCP Nanolithography and Its Application in Cell Biology Other BCP Platforms for Cell Culture Studies Coassembly of BCPS with Peptides and Proteins in Thin Films BCP Surfaces for Biocompatibility and Antifouling Applications Biocompatibility of Poly(2-hydroxyethyl methacrylate)-Based Copolymers Structural Implications for PU Biocompatibility BCP Surfaces for Marine Antifouling Applications BCP Micelle Surfaces for Controlled Release Applications Conclusion References science_21 Microarrays in Biomaterials Research Abbreviations Introduction Principle of Microarray Microarray Technology Method Biological question Sample preparation and microarray reaction Microarray detection, data analysis and modeling Application of Microarray Various Approaches to Biomaterial Research Functional Application of Microarray Essential stem cells study for biomaterial research Pathway dissection analysis Clustering analysis Future Prospects of Microarray References science_23 Magnetic Resonance of Bone Microstructure and Chemistry Glossary Abbreviations Introduction Fundamentals of Magnetic Resonance Quantitative MRI of Trabecular and Cortical Bone Microstructure Role of Architecture: Structural Studies in Specimens In Vivo Spatial Resolution Regime Characterization of Trabecular Bone Architecture in Terms of Scale, Topology, and Orientation Trabecular bone volume fraction and thickness Topology of trabecular networks Structural orientation Bone Water and Porosity NMR Spectroscopy and MRI of Bone Matrix and Mineral Summary and Conclusions References science_24 Fluorescent Nanoparticles for Biological Imaging Abbreviations Introduction Fluorescent Nanoparticles: Synthesis and Surface Modification Quantum Dots Fluorescent Silica Nanoparticles Metallic Fluorescent Nanoparticles Polymer Fluorescent Nanoparticles Fluorescent Nanoparticles: In Vitro Applications Replacing Fluorescent Dye in Cell Labeling and Imaging Imaging and Tracking Endocytosis Analyzing Biomolecular Interactions Fluorescent Nanoparticles as a Biosensor Fluorescent Nanoparticles: In Vivo Applications In Vivo Tumor Imaging In Vivo Tracking of Cell Migration in Living Animal In Vivo Imaging of Cardiovascular and Lymphatic Systems Future Perspective Acknowledgment References science_26 Imaging and Diagnosis of Biological Markers Glossary Abbreviations Symbols Introduction Principles of MR and the Implications for Imaging and Diagnosis The MR Interactions The Zeeman interaction Quadrupole interaction Interaction with an applied RF field Direct dipole-dipole interaction Magnetic shielding interaction Indirect spin-spin coupling Basics of MR Pulse Sequences Creating and detecting the MR response Relaxation in MR Longitudinal and transverse relaxation Rotating frame relaxation Diffusion in MR Magnetic Resonance Imaging Magnetic field gradients NMR signal and k-space Image contrast Example of MRI sequence Application to Imaging and Diagnosis of Biological Markers Summary Viable Molecules, Nuclei, and Experiments for MR Studies 1H Magnetic Resonance Water Fats Direct detection of small molecule metabolites 31P MR 23Na Magnetic Resonance Na+ concentration for diagnosis 23Na NMR parameters as biological markers for diagnosis 13C Magnetic Resonance Other Nuclei Summary Case Study: Biological Markers for the Diagnosis of DDD Molecular Changes During DDD 2H Double Quantum Filtered NMR Studies 1H T1rho Studies of Water to Assess DDD Na+ Concentration Studies to Assess DDD 23Na Multiple Quantum Filtered NMR Studies Conclusions Case Study: MR for Diagnosing Bone Disease and Treatment Bone Structure and Markers of Disease Diagnosis of Bone Disease Using MR Techniques Collagen imaging Studies of HAp MRS of marrow fat Diffusion imaging of water in marrow Developing and Assessing Biomaterial Treatments Bioinert and resorbable bone materials Bioactive bone implants Hybrid bone biomaterials Conclusions Summary and Future of Imaging and Diagnosis of Biological Markers References science_22 Infrared and Raman Microscopy and Imaging of Biomaterials Glossary Abbreviations Introduction Principles of Vibrational Spectroscopy Mid-IR spectroscopy Raman scattering IR spectroscopy versus Raman scattering Mapping and Imaging Instrumentation, Sampling, and Data Processing IR Microscopy Instrumentation IR Imaging Instrumentation FTIR Microscopy and Imaging Sampling Raman Microscopy Instrumentation Confocal Raman Microscopy FT-Raman Microscopy Raman Mapping and Imaging Mapping Raman Microscopy and Imaging Sample Preparation Spectral Data Processing Applications to Biomaterials IR Microscopy Applications IR Imaging Applications Raman Microscopy and Imaging Applications Raman microscopy Raman imaging Conclusions References Relevant Websites science_28 Biosensors Based on Sol-Gel-Derived Materials Abbreviations Introduction Sol-Gel Bioencapsulation Sol-Gel Immobilized Biorecognition Elements Enzymes Antibodies Whole cells Stability of Biorecognition Elements in Sol-Gel Matrix Interactions Between Sol-Gel Matrix and Analytes Applications of Sol-Gel Biosensors Electrochemical Biosensors Optical Biosensors Biosensors Based on Other Transducing Principles Conclusions and Future Trends References science_25 Imaging Mineralized Tissues in Vertebrates Abbreviations Introduction Structure of Mineralized Tissues Bone Hierarchical structure of bone Lamellar bone Woven and plexiform bone Tooth Calcified Cartilage Calcified Tendon Heterogeneity of Mineral Content and the Need for Imaging Techniques Estimates of Total Bone Mineral Content Ash Weight Analysis Density Fractionation Neutron Activation Bone Mineral Density Imaging of Mineralized Tissues Light Microscopy and Morphometry X-Ray Microradiography Phase-Contrast and Dark Field X-Ray Imaging Microcomputed X-Ray Tomography and Synchrotron Radiation Microtomography X-ray tomography for structural analysis X-ray tomography for quantitative analysis of the mineral content Magnetic Resonance Imaging Transmission Electron Microscopy Property Mapping in Mineralized Tissues Vibrational Spectroscopy Fourier transform infrared imaging Raman spectroscopy Secondary Electron and Back-Scattered Electron Imaging Scanning Small Angle X-Ray Scattering and Diffraction Mapping of Elastic Properties Scanning acoustic microscopy Nanoindentation Mapping of Elemental Composition X-ray fluorescence Secondary ion mass spectrometry Scanning Surface Topography with AFM Conclusions References science_27 Intracellular Probes Abbreviations Introduction Fluorescence-Based Intracellular Probes Introduction Physical Principles Fluorescent Molecules for Intracellular Probing Design criteria Fluorescent dyes FRET-Based Sensing Introduction Principle of FRET Detection Applications of FRET Problems associated with FRET Nanoplatforms-Based Fluorescent Probes Introduction Probe embedded by biologically localized encapsulation Design and synthesis Biological applications Ion sensors Dissolved oxygen sensors Reactive oxygen species sensors Electric field sensors Chemiluminescence sensors Sensors with encapsulated proteins Molecular beacons Structure and principle of operation Biomedical application Optical-Label-Free Intracellular Probes Surface Plasmon Resonance-Based Probes Working principle SERS nanosensor Intracellular chemical probing Quantum Dots as Intracellular Probes Introduction Synthesis of QDs Functionalization of QDs: Solubilization and bioconjugation Solubilization Biomolecule conjugation Toxicity/biocompatibility Biological applications Immunolabeling: In vitro Within living cells In vivo applications Conclusion References science_29 Hydrogels in Biosensing Applications Glossary Introduction Sensors: General Definition and Classification Biosensors Hydrogels: Definitions and Theoretical Aspects Hydrogels for Biosensors Structure of the Chapter Physicochemical Sensing Mechanisms Temperature Sensitivity Ion Strength and pH Gas and Humidity Gas Humidity Biochemical Sensing Mechanisms Molecular Interactions Enzyme-substrate interaction Alcohol Amino acids Ammonia Glucose Hydrogen peroxide Antibody-antigen DNA and oligonucleotides Other binding mechanisms Biotin-streptavidin Calmodulin-based sensing Carbohydrate recognition by boronic acids Fluorescence-based glucose sensing Peptide-modified hydrogels for toxin screening Living Sensors Bacteria Cells Hydrogel coatings and influence of the third dimension Cell preservation in 3D hydrogels Pathogen Nitric oxide/glutamate Summary References science_30 Carbon Nanotube-Based Sensors: Overview Glossary Introduction CNTs and Related Carbon-Based Nanostructures Brief Perspective Fabrication Properties Manufacturing Devices from Carbon Nanostructures Devices with Randomly Oriented CNTs Devices from Vertically Aligned CNTs and CNFs Carbon Nanostructure-Tipped Devices Enhancement and Selectivity Sensing Applications of Carbon Nanostructures Electrochemical Sensors Detection of Gases and Vapors Detection of Biomolecules Single-Cell Probes and Sensors Future Opportunities References science_31 Conjugated Polymers for Biosensor Devices Abbreviation Conjugated Polymers (CPs): History and Perspectives Introduction Synthetic Strategies and Processability of CPs Doping Reactions to Facilitate Conductivity and Specific Tasks Properties of CPs Electric conductivity UV/VIS absorption and fluorescence Signal amplifying properties Electrochemical Biosensors Amperometric biosensors Potentiometric biosensors Conductometric biosensor Optical Biosensors and Bioassays Colorimetric, fluorescence, and superquenching-based biosensors Using CPs for Electrochemical Biosensor Devices Introduction Immobilization Strategies for Biological Sensing Elements (BSEs) onto CP-Coated Electrodes Physical entrapment Ion exchange/physical adsorption Covalent attachments Affinity interactions BSE-functionalized CP monomer Choice of Entrapment Approach Current Research Directions of Electrochemical CP-based Biosensors Using CPs for Optical Biosensor Devices Introduction BSE-Functionalized Liposome CPs BSE/CP Complexes DNA biosensing using DNA probe/CP complexes Protein biosensing using BSE/CP complexes CP Covalently Modified with BSE References Volume 4 Biocompatibility, Surface Engineering, and Delivery of Drugs, Genes and Other Molecules science The Concept of Biocompatibility Glossary Introduction Criteria for Assessing Biocompatibility Factors Affecting Biocompatibility Examples of Biocompatible and Adverse Tissue Responses Wound-Healing Responses Underlying Biocompatibility Fundamental Stages of the Wound-Healing Response to Implantation Surgery: Acute Phase Repair Versus Regeneration The Chronic Response: Macrophages and Fibroblasts - Synovium Historical Perspective on Observations on the Tissue Response to Implants Characteristic Features of Tissue Around Implants: Emerging Insights Fibroblasts: Expression of α-Smooth Muscle Actin Presence of Lubricin in the Tissue Around Loose Orthopedic Prostheses Summary and Considerations for the Future Acknowledgment References Relevant Websites science_2 Biocompatibility and the Relationship to Standards: Meaning and Scope of Biomaterials Testing Abbreviations Introduction Biocompatibility Materials for Medical Devices In Vitro Tests for Biocompatibility In Vivo Tests for Biocompatibility Sensitization, Irritation, and Intracutaneous (Intradermal) Reactivity Systemic Toxicity (Acute Toxicity) and Subacute and Subchronic Toxicity Genotoxicity Implantation Chronic Toxicity Carcinogenicity Reproductive and Developmental Toxicity Biodegradation Inflammation, Wound Healing, and the Foreign-Body Response Overview Acute Inflammation Chronic Inflammation Granulation Tissue Foreign-Body Reaction Fibrosis/Fibrous Encapsulation Hemocompatibility Immune Responses Summary and Conclusion References science_3 The Innate Response to Biomaterials Glossary Abbreviations Introduction Biomaterial Changes Inflammation and Biomaterials Infection Persistent and Chronic Inflammatory Responses Nondegradable materials Biodegradable materials Evasion Innate Immune System Activation Enhancement of Innate Immune System Activation Concluding Remarks References science_4 Adaptive Immune Responses to Biomaterials Glossary Introduction Cells and Structures of Adaptive Immunity Organization of the immune system Mononuclear phagocytes Lymphocytes Cellular identification Recognition of Biomaterials by the Adaptive Immune System Indirect Effects on Lymphocytes Attraction of leukocytes to the implant site Activation of adaptive cells by innate cells activated through biomaterial contact Paracrine/juxtacrine mechanisms Physical macrophage-lymphocyte interactions Direct Effects of Lymphocytes Consequences of the Adaptive Response Spectrum of Adaptive Responses to Biomaterials Inflammatory responses Range of T cell responses (Th1, 2, 17 rejection, tolerance, effect of duration, and magnitude) Effects on Biomaterial-Only Devices (e.g., Probes, Implants, Biological Scaffold Materials) Inflammation Foreign body response Fibrosis Angiogenesis Autoimmunity Infection Effects on Combination Products (i.e., Vaccine or Tissue-Engineering Construct) Magnitude of response Altered responses Tolerance responses Approaches to Engineer Adaptive Responses with Biomaterials Biomaterials as Vaccine Adjuvants and Antigen Carriers Surface Modification Anti-inflammatory Drug Release Conclusions References science_5 Leukocyte-Biomaterial Interaction In Vitro Abbreviations Introduction Characterizing the Inflammatory Response Protein Adsorption Characterizing protein adsorption in vitro Cellular Indicators in the Inflammatory Response Neutrophil material interactions in vitro ROS production and measurements in vitro Cytokine production by neutrophils In vitro monocyte material interactions Monocyte isolation from human whole blood Characterizing monocyte adhesion in vitro, indicators of FBGC formation Inflammatory cell recruitment: Chemokines and cytokine production Monocyte/lymphocyte coculture models Foreign body giant cell formation in vitro Leukocyte Interactions with Wear Particles The role of in vitro leukocyte models: Controlling the inflammatory response References science_6 Protein Interactions with Biomaterials Glossary Introduction Proteins of the Human Body and Relevance for Biomaterials Nonspecific and Specific Surface-Protein Interactions Phenomena Related to Protein Adsorption Nonspecific and Specific Biomaterial Surface-Protein Interactions Surface Wettability, Topography, and Protein Adsorption General Hydrophobic Surfaces Negatively/Positively Charged Surfaces Surface Nano-Roughness and Protein Adsorption Protein Displacement Phenomena Protein-Resistant Surfaces Surface-Activated Coagulation Intrinsic Pathway Tissue Pathway Immune Complement at Biomaterials Prevailing Model of Activator/Inhibitor Surfaces Spontaneous, Classical, and Alternative Complement Activation Consequences of Protein Adsorption Blood Compatibility Inflammation and Wound Healing Adsorbed Proteins and Biomaterials-Related Infection Summary and Future Directions References science_7 Bacterial Adhesion and Biomaterial Surfaces Glossary Abbreviations Introduction Laboratory Methods for the Study of Bacterial Adhesion Static Adhesion Assay Bioreactors Flow Chambers Modified Robbins device Parallel plate flow chamber Measuring Bacterial Adhesion Forces Bacterial Characterization Methods Structural Characteristics Physicochemical Characteristics Bacterial adhesion to hydrocarbons: The BATH test Contact angles on bacterial lawns Zeta potentials Theory and Mechanisms of Bacterial Adhesion Physicochemical Models of Bacterial Adhesion The thermodynamic theory The DLVO theory The XDLVO theory Forces of Colloidal Adhesion Lifshitz-van der Waals: Apolar molecular forces Electrostatic forces Lewis acid-base: Polar forces Interpreting the Theories Mechanisms of Bacterial Adhesion Nonspecific Adhesion Specific Adhesion The Influence of Biomaterial Surface Properties on Bacterial Adhesion The Influence of Surface Chemistry on Bacterial Adhesion The Influence of Surface Topography on Bacterial Adhesion Strategies to Reduce Bacterial Adhesion Highly Charged Surfaces Low Surface Energy Materials Polymeric Coatings Including Polymer Brushes Bifunctional Polymer Brush-Like Coatings Plasma Activation and Coatings Summary and Perspectives References science_8 Integrin-Activated Reactions to Metallic Implant Surfaces Abbreviations Introduction Integrins Integrins Subunits and Adhesion Integrin Structure Integrin Function Cells Adhesion, Survival, Growth, and Differentiation Bone Cells Integrins and Growth Factor Receptors Integrin-Signaling Pathways Intracellular-Signaling Pathways Integrin Binding to Biomaterials Initial Binding of Serum Proteins to Implant Materials Integrin-Mediated Cellular Responses to Implant Materials Inflammatory Responses Functionalizing Implant Surfaces Using Adhesion Molecules General Description of Functionalizing Implant Surfaces In Vitro Studies Using Adhesion Molecules on Implant Surfaces In Vivo Studies Using Adhesion Molecules on Implant Surfaces Functionalizing Biomaterials with Short Versus Long Peptides Functionalizing Biomaterials with Multiple Peptides Conclusions References science_9 Surfaces and Cell Behavior Glossary Abbreviations Introduction Manufacturing Surface Topography Photolithography Laser Holography (LH) Electron-Beam Lithography Colloidal Lithography Polymer Demixing History of Differentiated Cell Guidance by Nanostructures Grooves Pits Pillars The History of Stem Cells and Nanotopography Embryonic Stem Cells Skeletal Stem Cells Neural Stem Cells Low Adhesion Materials Nanotopography as a Noninvasive Tool for Cell Biology Responding to the Cellular Environment Mechanotransduction in the Nucleus Transcriptomic and Proteomic Effects Conclusions and Future Perspectives Orthopedics Stem Cells and Regenerative Medicine Nanotopography for Cell Biology Acknowledgment References science_10 Sterilization of Biomaterials of Synthetic and Biological Origin Glossary Abbreviations Introduction Sterilization Methods Heat and Pressure Ionization Irradiation Chemical Sterilant Ethylene oxide Sterilant solutions New Methods Supercritical carbon dioxide Gas plasma (ionized gas) Other Selection Criteria of Sterilization Method for Biomaterials Sterilization Validation Sterilization of Biomaterials of Synthetic and Biological Origin Synthetic Biomaterials Metals Polymers Ceramics/bioactive glasses Materials of Biological Origin Soft tissues Hard/dense tissues Demineralized bone matrix Evaluation of Effect of Sterilization on Biomaterials Selection of Analytical Methods Effect of gamma-Irradiation on a Regenerative ECM Matrix: A Case Study References Relevant Websites science_11 Peptide- and Protein-Modified Surfaces Glossary Amino Acid Abbreviations Abbreviations Introduction Peptides Versus Proteins Immobilization Strategies Adsorption Covalent Tethering Affinity or Capture Immobilization Functional Parameters Surface Density Spatial Arrangement Dynamic or Temporal Presentation Biological Activity: Conformation and Orientation Sample Applications Orthopedic Applications Cardiovascular Applications Neural Applications Conclusions and Outlook Acknowledgment References science_12 Rational and Combinatorial Methods to Create Designer Protein Interfaces Glossary Abbreviations Introduction Rational Engineering Site-Directed Mutagenesis Analyzing amino acid sequences Sequence homology Cysteines and disulfide bonds Applying three-dimensional structures Predicting through computational modeling Fusions and Domain Swapping Peptide fusions Protein fusions Posttranslational Modifications Glycosylation PEGylation Other emerging modifications Combinatorial Engineering Library Creation Random mutagenesis Directed mutagenesis Recombination Screening Platforms Plate-based platforms Phage display Cell surface display E. coli surface display Yeast surface display In vitro platforms Ribosome display mRNA display In vitro compartmentalization Protein Engineering Considerations for Biomaterials: The Interface Between Proteins and Materials Protein Encapsulation or Attachment Protein-Based Biomaterials Conclusions and Future Directions References science_13 Patterned Biointerfaces Glossary Abbreviations Introduction Patterning Techniques Top-Down Approaches Photolithography Resist-based patterning (MAPL) Direct patterning Extreme ultraviolet interference lithography Beam-based lithography Electron beam lithography Laser beam lithography Embossing Soft lithography Direct microcontact and nanocontact printing Subtractive printing Microfluidics Stenciling Scanning-probe lithography Dip-pen nanolithography Nanodispensing techniques Nanografting lithography Bottom-up Approaches Colloidal lithography Block copolymer micelle nanolithography Block copolymers DNA templating Biointerfacing with Patterned Surfaces Vesicle and Membrane Patterns Vesicle arrays Supported membrane arrays Cell Adhesion and Function on Patterned Surfaces Cell shape and its impact on cell survival/apoptosis Cell adhesion to nanopatterned surfaces Cell differentiation on micropatterned surfaces Effect of micropatterned surfaces on cytoskeletal architecture Cell motility on micropatterned gradients Tissue engineering Bacteria at Patterned Interfaces Viruses at Patterned Interfaces Acknowledgment References science_14 Molecular Biomimetic Designs for Controlling Surface Interactions Glossary Abbreviations Introduction Biomaterials' Failure Mechanisms Protein Adsorption and Thrombus Formation Approaches for Controlling Surface Biological Interactions Rods and Coils Biomimetic Surface Modifications Cell membrane biomimetic surface modifications Glycocalyx Biomimetic Models Glycocalyx-like biomimetic biomaterials Coating blood compatibility ECM Biomimetics ECM-Like Biomimetics Integrin-dependent interaction of EC on biomimetic surfactant polymers Surface peptide ligand density Shear stability of surface-attached cells Biomimetic Modifications of Clinically Relevant Biomaterials Cell-selective peptides Summary and Outlook Acknowledgment References science_15 Surface Engineering Using Peptide Amphiphiles Glossary Abbreviations Introduction The Amphiphilic Nature of Life's Events PAs: Synthesis, Physicochemical Characterization, and Self-Assembly Synthesis and Characterization of PAs Double-Tailed (Dialkylated) PAs Single-Tailed (Monoalkylated) PAs The Multifunctional (Soft) Nanoparticle Concept Targeting-Enabled PA Spherical Micelles Single-Tailed PAs for Cancer Cell Biology Control In Vitro Binding Affinity Control via Native Chemical Ligation Protein-Like Structures to 3D Hierarchical Nanostructures Applications in Biomedical Sciences: Tissue and Stem Cell Engineering Helical Structure and Antibacterial PAs Neural Stem Cell Engineering Bone Marrow Mononuclear Cells Ameoblast Cell Engineering for Tooth Regeneration Heparin-Binding PAs for Regenerative Medicine Human Mesenchymal Stem Cell Engineering Dental Stem Cells Bioactivation of Metallic Surfaces Summary and Future Directions Acknowledgment References science_16 Growth Factors and Protein-Modified Surfaces and Interfaces Glossary Abbreviations Introduction Proteins for Surface Immobilization Cell Adhesion ECM-cell interactions Cell-cell interactions Cadherins Selectins Immunoglobulin superfamily Others Notch Sonic hedgehog Cell adhesion peptides Cell Growth Mechanisms Growth factors for immobilization on surfaces Insulin Insulin growth factor 1 Epidermal growth factor Nerve growth factor Bone morphogenic protein Vascular endothelial growth factor Fibroblast growth factor Transforming growth factor beta Hepatocyte growth factor Platelet-derived growth factor Cell Adhesion and Growth Protein Immobilization (Chapter 2.209, Materials as Artificial Stem Cell Microenvironments; Chapter 4.411, Peptide- and Protein-Modified Surfaces; and Chapter 5.508, Scaffold Materials for hES Cell Culture and Differentiation) Immobilization for ECM–Cell Interactions (Chapter 2.207, Extracellular Matrix: Inspired Biomaterials; Chapter 2.208, Artificial Extracellular Matrices to Functionalize Biomaterial Surfaces; and Chapter 2.220, Extracellular Matrix as Biomimetic Biomaterial: Extracellular matrices Biomimetic peptides (Chapter 4.415, Surface Engineering Using Peptide Amphiphiles) Immobilization for Cell-Cell Interaction Cadherin Selectin Notch ligand Ephrin B2 Sonic hedgehog Surface Immobilization of Growth Factors Mechanisms Examples of immobilized growth factors Insulin Insulin-like growth factor 1 Epidermal growth factor Nerve growth factor Bone morphogenic protein Vascular endothelial growth factor Fibroblast growth factor Transforming growth factor beta Hepatocyte growth factor Platelet-derived growth factor Keratinocyte growth factor Leukemia inhibitory factor Stem cell factor Erythropoietin Interleukins Tumor necrosis factor α Summary and Future Directions References science_17 Tethered Antibiotics Glossary Abbreviations Implant-Associated Infection in Orthopedic Materials The RANKL Pathway and the Pathogenesis of Osteomyelitis Biofilm Development Bacterial Responses to Orthopedic Implants Metallic Implants Bone Allograft Antibiotic Prophylaxis and Treatment of Surgical Infection Structure of VAN VAN's mechanism of action Antibiotic resistance to VAN Surface Tethering of Antibiotics to Prevent Bacterial Adhesion Device Surface Preparations for Tethering Properties of Surface-Tethered VAN Properties of surface-tethered antibiotics Biocompatibility of Tethered VAN Coupling with Other Technologies Acknowledgment References science_18 Engineering Interfaces for Infection Immunity Glossary Abbreviations The Problem Nosocomial Infections Current Anti-infective Biomaterials Strategies Bacterial Evasion of Host Immune Defenses Biofilm-immune cell interactions Thinking Outside the Cube Innate and Adaptive Immune Responses Immunology 101 Innate Immune Responses to Biomaterials: `Anger Management´ Adaptive Immune Responses to Biomaterials: Biomaterial Vectors for Transfecting DCs Phenotype/characteristics of peripheral versus LN DCs Vaccine Adjuvant Design Biomaterial vectors for targeted antigen delivery in vivo Engineering Infection Immunity Enhanced Innate Response Biomaterials that Vaccinate Concluding Remarks References science_19 Vaccine and Immunotherapy Delivery Glossary Abbreviations Introduction The Paradigm of Immune Responses in Infection Versus Vaccination Biomaterials as Delivery Vehicles for Vaccines and Immunomodulators Vaccine Delivery Across Mucosal Barriers and Skin Controlling Vaccine Delivery at the Tissue/Organ Level Creation of antigen depots Targeting and `reverse targeting´ of APCs Lymph node targeting Controlling Vaccine Delivery at the Cellular Level Cross-presentation of antigen to CD8+ T cells B cell activation and humoral responses Biomaterials as Immunostimulators and Carriers of Immunostimulatory Adjuvants for Vaccines Intrinsic Adjuvant Activity of Biomaterials Activation of the inflammasome Role of TLRs in immune cell response to biomaterials used as vaccine carriers Complement-activating biomaterials Biomaterial-mediated adjuvant mechanisms not yet elucidated Biomaterials as Carriers of Adjuvant Molecules Delivery of PAMPs, DAMPs, and related immunostimulatory molecules Delivery of immunoregulatory cytokines Future Directions Conclusions Acknowledgment References science_20 Drug Delivery via Heparin Conjugates Glossary Rationale for Using Heparin Conjugates for Drug Delivery Methods for Heparin Immobilization Covalent Heparin Immobilization on Beads (Sepharose) Noncovalent Immobilization of Heparin Covalent Immobilization of Heparin by EDC/NHS Chemistry Covalent Immobilization of Heparin via Generation of Aldehyde Groups Covalent Immobilization of Heparin via Methacrylate Groups Covalent Immobilization of Heparin via Thiol Groups Covalent Immobilization of Heparin via Maleimide Groups Covalent Immobilization of Heparin Via Hydrazide Groups Covalent Immobilization of Heparin as a Gelation Agent Use of Heparin Mimetic Molecules for Delivery of Heparin-Binding Growth Factors Summary References science_21 Self-Assembled Prodrugs Glossary Abbreviations Introduction Molecular Versus Polymeric Gelators: Perspectives in Hydrogels An introduction to hydrogels Polymeric hydrogels Molecular hydrogels Challenges and Opportunities of Hydrogels in Drug Delivery Delivery of Hydrophobic Drugs Challenges and Opportunities Self-Assembled Prodrugs Motivation to Design Self-Assembling Prodrugs as Biomedical Gelators Structure-Based Self-Assembled Prodrugs General Strategy to Design Self-Assembled Prodrugs Acetaminophen-based self-assembled prodrugs Amygdalin-based self-assembled prodrugs Ibuprofen-based self-assembled prodrugs Paclitaxel-based self-assembled prodrugs Morphology-Based Self-Assembled Prodrugs Self-assembled nanoparticles from prodrugs Self-assembled vesicles from prodrugs Self-assembled micelles from prodrugs Self-Assembled Irreversible Prodrug-Based Hydrogels Paclitaxel-Based Self-Assembled Hydrogels Vancomycin-Based Self-Assembled Hydrogels Glucosamine-Based Self-Assembled Hydrogels Conclusions and Outlook Acknowledgment References science_22 pH-Responsive Polymers for the Intracellular Delivery of Biomolecular Drugs Glossary Introduction Acid-Base Equilibria and pH-Responsive Chemistries Anionic pH-Responsive Polymers Poly(alkylacrylic acid)s Poly(styrene-alt-maleic anhydride) Acid-Degradable Delivery Vehicles Encrypted Polymers Buchwald Coupling-Based Vehicles Acid-Cleavable Lipid Drug Delivery Vehicles Osmotically Disruptive Cationic Polymers Poly(l-lysine) Polyethyleneimine Poly(amidoamine) Dendrimers and Polymers Poly(beta-amino esters) Chitosan Histidine- and Imidazole-Containing Copolymers Fusogenic Peptides GALA Future Perspectives References science_23 Polymeric Drug Conjugates by Controlled Radical Polymerization Abbreviations Introduction Overview of Controlled Radical Polymerization Reversible Addition-Fragmentation Chain Transfer Polymerization Atom Transfer Radical Polymerization Nitroxide-Mediated Polymerization Examples of Polymer Conjugates Synthesized by Controlled Radical Polymerization Polymer-Small Molecule Drug Conjugates Polymer-Protein Drug Conjugates Polymer-Peptide Drug Conjugates Prospects and Challenges Acknowledgment References science_24 Nanoparticles for Nucleic Acid Delivery Abbreviations Introduction Therapeutic Opportunities for Nucleic Acids DNA therapies Antisense and small-interfering RNA therapies Formulation Issues for Nucleic Acid Therapeutics Barriers to nucleic acid delivery General Classes of Nucleic Acid Delivery Systems Viral Vectors for Nucleic Acid Delivery Nonviral Vectors for Nucleic Acid Delivery Classes of Nonviral Vectors Cationic Lipids and Liposomes Cytocompatibility of cationic lipids and liposomes Synthetic Peptides Lysine-containing peptides Arginine-containing peptides (CPPs) Histidine-containing peptides (endosomal escape peptides) Cysteine-containing peptides Chitosan and Derivatives Synthetic Polymer/Polyplex Carriers Polycations for condensing nucleic acids DEAE-dextran Polyethyleneimine Amino-functionalized methacrylates and methacrylamides Dendrimers Polymers for nucleic acid encapsulation Micro- and nanoparticle-based gene delivery Fabrication of nucleic acid-loaded PLGA NPs: challenges and opportunities Double emulsion techniques for matrix NP nucleic acid delivery Spray-drying techniques for matrix NP nucleic acid delivery Adsorption of nucleic acids on PLGA particle surfaces Challenges associated with matrix particles as nonviral gene delivery systems Polymer micelles and vesicles as NP nucleic acid delivery systems Stimuli-responsive polymersomes Opportunities and Challenges in NP Therapeutics: Biological Barriers to Nucleic Acid Delivery Systemic Barriers Cellular Barriers to Uptake of Nucleic Acids Overcoming Systemic and Local Biological Barriers: Surface Coating of NPs with Hydrophilic Polymers and Targeting Sterically stabilized PEGylated polyplexes Overcoming local biological barriers: surface modification of NPs with targeting ligands Chimeric/hybrid NPs for overcoming systemic barriers gene delivery Formulation Issues for Nucleic Acid Therapeutics - Binding Between Vector and Nucleic Acid: A Balancing Act... Conclusions Acknowledgment References science_25 Delivery of Nucleic Acids and Gene Delivery Glossary Abbreviations Introduction Packaging Concept Nucleic Acids Plasmid DNA Oligodeoxyribonucleotide Small interfering RNA and microRNAs Carrier Systems Liposomes Polymers Polymeric micelles Multifunctional envelope-type nanodevice Pharmacokinetics Factors Governing the PK of a Carrier System Carrier charge Carrier size Passive Carrier Targeting Strategy for addressing the PEG dilemma Targeting by specific ligands Facilitating endosomal escape Endothelial Barriers Intracellular Trafficking Routes of Cell Uptake Endosomal Escape Cytoplasmic Transport Nuclear Delivery Intranuclear Disposition Heterogeneity in Transfection In Vivo Applications In Vivo Delivery of pDNA Cancer Liver Lung Kidney Muscle In Vivo Delivery of siRNA Chemical modification, bioconjugation and targeted in vivo siRNA delivery Lipid-based in vivo siRNA delivery Polymer-mediated in vivo siRNA delivery Other delivery systems Clinical trials of siRNA therapeutics Acknowledgment References science_26 Electrospun Fibers for Drug Delivery Glossary Abbreviations Introduction Historical Perspective Scope of Electrospun Fiber Use Principles of Electrospinning Polymers used in Electrospinning Electrospinning Parameters Used to Alter Fiber Morphology Permutations of the Electrospinning Process Rotating collectors Ring collectors Dual collectors Adhesive collectors Patterned collectors Electrospinning writing Three-Dimensional Scaffolds of Electrospun Fibers Electrospinning onto ice crystals Hydrospinning Simultaneous electrospinning/electrospraying Electrospinning microfibers Electrospinning onto scaffold carriers Drug Delivery from Electrospun Fibers Drug Inclusion within the Polymeric Solution Bioavailability of Drugs at the Fiber Surface Chemical binding Drug adsorption Nanoparticle formation Multilayer assembly Surface-segregated chemistry for functionalization Release Rates and Bioactivity of Incorporated Drugs Coaxial Electrospinning Emulsion Electrospinning Morphological Variations Affecting Drug Delivery Additives to Modify Electrospinning Materials Conclusions and Future Directions References science_27 Cell-Demanded Release of Growth Factors Glossary Abbreviations Introduction Medical Motivation Technological Motivation for Development of Biomaterial Mimetics of Natural ECM Enabling Polymer Hydrogels for Cell-Demanded Release Collagen Engineering Fibrin Engineering Polysaccharide-Based Semisynthetic Materials Fully Synthetic ECM Mimetic Hydrogels Fully Synthetic Fibrin Mimetic Hydrogels Preclinical Evaluation in Angiogenesis Clinical Need for Angiogenic Therapy Lessons from Embryonic Development and Early Therapeutic Angiogenesis Research Cell-Demanded Release in Vascularization Conclusion and Future Directions Acknowledgment References science_28 Sol-Gel Processed Oxide Controlled Release Materials Glossary Abbreviations Symbols Introduction Sol-Gel Process Overview Hydrolysis Condensation Physicochemical State of Sol-Gels and Incorporated Drugs Sol-gel Incorporated drugs Ordered Mesoporous Silica Drug Release Mechanisms Diffusion-Controlled Release Degradation-Controlled Release Mixed Release Kinetics Difference Between In Vitro and In Vivo Kinetics Control of Release Kinetics Effect of pH of the Sol Effect of Water/Alkoxide Molar Ratio Effect of Drying Conditions Effect of Additives Polymers Organically modified alkoxy silanes Surface modification Stimuli-responsive delivery Biocompatibility and Resorption Biocompatibility Systemic Biocompatibility of Resorbable Silica-Based Glasses Applications Sol-Gel Application Forms Monoliths Particle Microparticles Emulsion sol-gel process Spray-drying sol-gel process Nanoparticles Fibers Thin films Hydrogels Mixed oxide sol-gels Composites Therapeutic Agents of Various Size Small therapeutic agents Intermediate sized therapeutic agents (proteins or growth factors) Large therapeutic agents (DNA or virus) Clinical Applications Pain management Bacterial infection control Cancer therapy Summary References science_29 Ordered Mesoporous Silica Materials Glossary Abbreviations Symbols Introduction Ordered Mesoporous Materials: General Remarks Biocompatibility of Mesoporous Materials Mesoporous Materials for Local Drug Delivery Influence of the Textural Properties Pore diameter Surface area Pore volume Influence of the Matrix Structure Influence of the Particle Morphology Influence of the Matrix Organic Functionalization Functionalization with amino groups Functionalization with hydrophobic groups Bioactivity of Mesoporous Matrices Incorporation of Phosphorous into Mesoporous Silica Matrices Addition of Small Amounts of Bioactive Glasses Mesoporous Bioactive Glasses Hierarchical Macroporous Scaffolds for Bone Tissue Engineering References science_30 Silica-Based Mesoporous Nanospheres Abbreviations Introduction History Synthesis of Nonporous Silica Nanospheres The Stöber Technique Synthesis of MSNs General Principles of Synthesis of Mesoporous Silica Formation Mechanisms of Mesoporous Silica Liquid crystal templating mechanism Transformation mechanism from lamellar to hexagonal phase Synthesis and Growth of MSNs Alternative methods Growth mechanism Morphology Control Particle size Mesoporous silica microsphere Mesoporous silica nanospheres Physicochemical Properties and Characterization Properties Product crystallinity Thermal and hydrothermal stability Characterization Gas adsorption methods Surface area Pore volume Pore size Unique Biomaterial Considerations Host-Guest Encapsulation Surface Functionalization Biocompatibility Conclusion References science_31 Encapsulation of Cells (Cellular Delivery) Using Sol-Gel Systems Glossary Abbreviations Introduction Declaration of Intents Sol-Gel Materials Sol-Gel Silicates Silicon and Life Biocompatible Preparation of Sol-Gel Silica Additives: The Design of Silicate Composites Self-Organizing Systems Design of Prosthetic Organs: A Case Study Silica precursors in the gas phase: the BioSil method Aminopropyl-silicate membrane electrically bonded by external anionic polymers Rational engineering of tissues and organs Cell Delivery in Temperature-Sensitive Sol-Gel Systems Mechanisms of Sol-Gel Transition in Temperature-Sensitive Materials Composition of Temperature-Sensitive Gels Natural and semisynthetic polysaccharides Chitosan-based cell-assisted cartilage repair vehicles Copolymers of N-isopropyl-acrylamide PNIPAA composites Polyoxyethylene-polyoxypropylene (poloxamer or Pluronic) aqueous gels Graft copolymers with poloxamer blocks Triblock copolymers containing poly-hydroxylic acids Availability of Injectable Cell Carriers for Practical Medicine Conclusion and Future Directions Acknowledgment References Relevant Websites science_32 Layered Double Hydroxides as Controlled Release Materials Abbreviations Introduction LDHs and Intercalation Structure Preparation and Intercalation Stabilization of Biomolecules via Intercalation Controlled Release of Intercalated Biomolecules Enhanced Cellular Uptake Conclusion and Perspectives References science_33 Porous Metal-Organic Frameworks as New Drug Carriers Abbreviations Introduction Adsorption and Delivery of Therapeutic Molecules Model Drugs The Role of Flexibility Nanoplatforms Synthesis of nanoparticles Surface engineering Adsorption of challenging drugs In Vitro Activity Tests BioMOFs The use of active linkers The use of biologically active metals Adsorption and Delivery of Biological Gases Toxicity and Stability Issues In Vitro Biodegradability In Vitro Toxicity Tests In Vivo Toxicity Assays Formulation Conclusion and Perspectives Acknowledgment References science_34 Hybrid Magnetic Nanoparticles for Targeted Delivery Abbreviations Symbols Introduction Magnetism of MNPs Behavior in Static Magnetic Fields and Gradients Materials magnetism background Magnetism of nanoparticles Surface effects Forces exerted in magnetic field gradients Behavior in AC Magnetic Fields Specific absorption rate Loss mechanisms MF Design and Preparation Synthesis of MNPs Colloidal Stabilization in Physiological Medium Size/Surface Requirements with Regard to i.v. Administration Biocompatibility Biodistribution and Passive Targeting Strategies Active Targeting Strategies Surface Activation and Bioconjugation MNPs as Contrast Agents for MRI MRI Background MR Contrast Agents Liver MR Imaging Metastatic Lymph Node MR Imaging (MR Lymphography) Blood Pool Imaging Macrophage MR Imaging Molecular MR Imaging Stem Cell Tracking Next Developments MNPs as Mediators for Magnetic Hyperthermia Hyperthermia Modalities Magnetic Fluid Hyperthermia Nanocomposite magnetic microparticles administered by arterial embolization Superparamagnetic nanoparticles injected directly into the tumor Next Developments Mediators improvement Physics of magnetic loss phenomena Targeting strategies and limits MNPs Within Carriers for Drug Delivery Magnetic Guidance for Carriers Enhanced Drug Release Under the Mechanical Stress of an Oscillating Magnetic Field Heat-Triggered Drug Release Under AC Magnetic Field Control Conclusion References Relevant Websites Volume 5 Tissue and Organ Engineering science Scaffolds: Flow Perfusion Bioreactor Design Abbreviations Introduction Mass Transport within Scaffolds Perfusion Bioreactors Design Parameters of Flow Perfusion Bioreactors Direct Perfusion of Scaffolds Media Flow Pathway Maintenance of Sterility Environmental Control Nutrient supply and waste removal Gas exchange Current Flow Perfusion Bioreactor Designs and Functions Dynamic Cell Seeding Tissue Culture Cartilage Bone Cardiac tissue Future Progress Improving Efficiency Scaling Up Standardizing Bioreactor Systems Determining Shear Stresses within Constructs Conclusions Acknowledgment References science_2 Engineering Scaffold Mechanical and Mass Transport Properties Glossary Abbreviations Introduction The Need for Engineering Scaffolds with Controlled Effective Properties Choosing Effective Properties as Design Targets Hierarchical Computational Scaffold Design Computational Representation of Hierarchical Scaffold Structure Computing Effective Scaffold Properties Using Homogenization Bounds on Effective Design Targets Designing Scaffold Architecture Integrating Hierarchical Design Hierarchical Scaffold DesignSummary Fabricating Designed Scaffolds Direct Solid-Free-Form Fabrication Indirect Solid-Free-Form Fabrication Postfabrication Surface Modification Scaffold FabricationSummary Designed Scaffold Architecture Influences Tissue Regeneration Cartilage Bone Neural Tissue Summary Conclusion Acknowledgment References science_3 Biomaterials and the Microvasculature Abbreviation Introduction Biomedical Engineering Applications Dependent on Neovascularization In or Around Biomaterials Tissue Engineering Cell-Based Gene Therapy Isolation Devices and Biosensors Survey of Neovascularization Types of Neovascularization Neovascularization and the Foreign Body Response In Vitro Models of Neovascularization Properties of Biomaterials Regulating Microvascular Network Formation In, On, and Around Biomaterials... Structural and Mechanical Features of Biomaterials Macrostructure Porosity of biomaterial Microstructure of biomaterial: pore size Microstructure of biomaterial: fibrous materials Biomaterial stiffness Chemical and Biochemical Features of Biomaterials Endothelial cell adhesion to biomaterials in vitro Endothelial network formation on and in functionalized biomaterials The role of chemistry in FBR in vivo Angiogenic factors Case Studies Implantation of Preformed Microvascular Networks Extravascular Wraps for Grafted Veins Glucose Sensors Acknowledgment References science_4 Effect of Substrate Modulus on Cell Function and Differentiation Glossary Abbreviations Introduction Young's Modulus Definition and Measurement Microspheres under gravitational forces Microindenters Atomic force microscopy Additional considerations for measurement techniques Development, Maintenance, and Variation of Young's Modulus in Biology Development and maintenance of tissue stiffness Aging and disease Fabrication of Substrates with Defined Material Modulus Natural ECM Components Collagen Hyaluronic acid Alginate Matrigel Synthetic Hydrogels Polyacrylamide Polydimethylsiloxane Other systems Cell Functions and Differentiation Neutrophils Fibroblasts Neural Cells Myoblasts Stem Cells Cancer Cells Other Cell Types Conclusion References science_5 Quantifying Integrin-Ligand Engagement and Cell Phenotype in 3D Scaffolds Abbreviations Introduction Quantifying Integrin-Ligand Forces Atomic Force Microscopy Magnetic Twisting Cytometry Traction Force Microscopy Fluorescence Resonance Energy Transfer Quantifying Type and Number of Integrin-Ligand Binding Immunochemical Techniques Fluorescence Resonance Energy Transfer Conclusion References science_6 Effects of Mechanical Stress on Cells Abbreviations Introduction Mechanical Environment of the Cell Mechanical Properties of the Cell Cytoskeleton Cell membrane Glycocalyx Subcellular Structures Involved in Mechanotransduction Interactions with the ECM: FAs Interaction with Neighboring Cells: Adherens Junction Primary Cilia Caveolae Nucleus Molecular Mechanotransduction Mechanosensitive Ion Channels Exposure of Cryptic Sequences Receptor-Ligand Interactions that Strengthen if Strained Response of Cells to Mechanical Stress and Implications for Tissue Engineering References science_7 Tissue Engineering and Selection of Cells Abbreviations Why Do Tissue Engineering Approaches Need a Cell Source? Cell Sources Used in Tissue Engineering Strategies Overview of Autologous Versus Allogeneic Versus Xenogeneic Sources Tissue-Specific Cells from SELF Stem Cells: Defined as a Collective Mesenchymal Stem Cells Embryonic Stem Cells Induced Pluripotent Stem Cells Endogenous Host Populations Patient Delivery Challenges: Controlling Cells in the Body How Do We Control Cells to Survive In Vivo After Transplantation? How Do We Control Cells to Maintain Appropriate Phenotype In Vivo? How Do We Control Cells to Migrate NOT to Migrate In Vivo? Donor Versus Host Immune Issues Immunomodulatory Role of MSC Populations Donor Versus Host: Cell/Tissue Integration Safety and Stability Conclusion Acknowledgment References Relevant Websites science_8 Scaffold Materials for hES Cell Culture and Differentiation Glossary Abbreviations Introduction Defining Stem Cells and Potency Derivation of hESCs Standard Culture Methods for hESCs Techniques for Evaluating the Differentiation State of hESCs Markers for observing the differentiation state of hESCs Experimental techniques for observing the differentiation state of hESCs Immunostaining Polymerase chain reaction Functional assays for confirming hESC identity Using Biomaterials for the Culture and Differentiation of hESCs Comparison of Natural Versus Synthetic Biomaterials Biomaterials for Undifferentiated hESC Culture Natural Biomaterials for Undifferentiated hESC Culture Heterogeneous biomaterial scaffolds Homogeneous biomaterial scaffolds Synthetic Biomaterials for Undifferentiated hESC Culture Biomaterials for hESC Differentiation Natural Biomaterials for hESC Differentiation Alginate Dextran Collagen/laminin/matrigel Fibronectin Other naturally derived materials Synthetic Biomaterials for hESC Differentiation Poly(lactic-co-glycolic acid) Poly(ethylene glycol) Other synthetic materials Conclusions and Future Work Reflections on the Current State of Biomaterial Scaffolds for hESC Culture and Differentiation Future Directions Issues with hESC culture to be addressed Potential new materials for use in combination with hESCs Additional natural biomaterials Additional synthetic biomaterials Summary References Relevant Websites science_9 Cell Encapsulation Glossary Abbreviations Introduction Methods Process Encapsulation Systems Natural Materials Collagen Fibrin Chitosan Hyaluronic acid Alginate Synthetic Polymer Materials Poly(ethylene) glycol Polyacrylates Polyfumarates Composites Representative Applications Diabetes Mellitus Liver Neurological Diseases Cancer Cartilage Summary References science_10 Engineered Bioactive Molecules Glossary Abbreviations Introduction Proteins Extracellular Matrix Proteins Biomimetic Peptides Growth Factors Transcription Factors Methods for Synthesizing Engineered Proteins and Peptides Nucleic Acids Plasmid DNA Viruses RNA DNA as a Material Lipids and Liposomes Acknowledgment References science_11 Rotating-Wall Vessels for Cell Culture Glossary Abbreviations Symbols Introduction Operating Principles of RWV Forces Acting on Microcarrier/Cell Modeling of Cell Culture Employing the HARV Determination of microcarrier trajectory and velocity Particle-particle and particle-wall collisions Microcarrier/cell spin Shear stress Mass transfer evaluation Optimal Conditions of RWV Scaffolds and Microcarriers for Cell Culture in RWV Criteria for Carriers Microcarriers and Scaffolds Used for Cell Culture in RWV Polymers Microcarriers Scafffolds Polymer-ceramic/glass composites Ceramics Cell Culture in RWV 3D Cell Culture Bone cells Cells cultured on polymer microcarrier and scaffolds Cells cultured on carriers lighter than culture medium Cells encapsulated in microcarriers or matrix No carrier used Chondrocytes Stem cells Other Tissue Engineering Other Applications of RWV Space Biology Cancer Research Other References Relevant Websites science_12 In Vivo Bioreactors Abbreviations Introduction Elements of the In Vivo Bioreactor Stem Cells or Progenitor Cells Applications and Tissues Skin Bone Small Intestine Transplant tolerance induction and restoration of metabolic and organ function by cotransplantation of thymus wi Urinary Tract The arteriovenous loop model: an 'in vivo bioreactor' to generate vascularized tissues and organs References science_13 Systems Biology in Biomaterials and Tissue Engineering Abbreviations Introduction Discrete Component-Centered Approach High-Throughput Component-Centered Approach Manufacturing Substrates Measuring Substrate Properties Surface chemistry and techniques Mechanical characterization Measuring Cellular Response Genomics Proteomics Metabolomics In Vivo Integration into Living Hosts Image informatics: Transcending scales with improved speed and resolution Process-Centered Systems Approach Modeling of Systems in Tissue Constructs Pathway Modeling for Process-Centered Approaches Pathway Modeling for Activation of TGF-beta1 in Liver Fibrosis Future Outlook References science_14 Chondrocyte Transplantation and Selection Glossary Abbreviations Introduction Cell Therapy and Cartilage Regeneration: State of the Art Cell Therapy Concepts in Cartilage Disease and Osteoarthritis Molecular Control Mechanisms in the Knee Joint - Implications for Cartilage Repair and OA The Uniqueness of Hyaline Cartilage Chondrocytes Adult Stem Cells and Stem Cell Niches Improvements in ACT Cell Technology - Alternative Cell Sources Autologous Use of Cells Osteoarthritic Cells Bone Marrow Stromal Cells or Mesenchymal Stem Cells Fat Stromal Cells and Cartilage Regeneration Universal Donor Cell Lines for Cartilage Repair Derivation of Chondrocytes from Human Embryonic Stem Cells Derivation of Chondrocytes from Umbilical Cord Cells and Umbilical Cord Blood Cells Conclusion References science_15 Cartilage Tissue Engineering Glossary Abbreviations Introduction Articular Cartilage Maturation and Synovial Fluid Formation Articular Cartilage Structure and Maturation Overview Composition Structure Function Cartilage maturation Synovial Fluid Composition and Formation Overview Composition Plasma proteins Lubricant macromolecules Cytokines and growth factors Cells Formation, molecular transport, and mechanobiology Formation Transport characteristics of synovium Mechanobiology of lubricant-secreting cells Mechanical Properties and Models of Articular Cartilage and Synovial Fluid Biomechanics of Articular Cartilage Types of mechanical loading during joint articulation Physiological loading of articular cartilage during gait Rheology and Tribology of Synovial Fluid Rheological properties Tribological properties Modeling Joint Tissue Biology Models of individual joint tissues Multicomponent models of the synovial joint Extending current models of the synovial joint Overview A generalized compartmental model of transport in the joint Mass balance equations Diffusive and convective transport equations Physical coupling of the compartments Example of model setup Mechanical Effects on Cartilage Maturation and Synovial Fluid Pathology Effect of Mechanical Stimuli on Cartilage Maturation Overview Effects of mechanical loads on cartilage metabolism Hydrostatic pressure Static compression Dynamic compression Dynamic shear Effects of mechanical loads on cartilage composition, structure, and function Synovial Fluid Pathology Overview Changes in composition Plasma proteins Lubricant macromolecules Cytokines and growth factors Proteolytic enzyme activity Changes in formation and molecular transport Changes in rheology and tribology Engineering Cartilaginous Tissue and Synovial Fluid Engineered Cartilaginous Tissue General overview Bioreactors Effects of physical stimuli on cartilaginous tissue growth and maturation Hydrostatic pressure Perfusion Static compression Dynamic compression Dynamic shear Sliding Tissue Engineering Synovial Fluid Overview Viscosupplementation Biomimetic approaches References science_16 Biomaterials in Cartilage Tissue Engineering Abbreviations Introduction Cell Sources Scaffolds Hydrogels Sponges Fibers Growth Factors Clinical Repair Techniques Conclusion References science_17 Tissue Engineering of the Temporomandibular Joint Glossary Abbreviations Introduction Gross Anatomy and Physiology of the TMJ Characterization of TMJ Tissues TMJ Disc Cells Collagen Glycosaminoglycans and proteoglycans Tissue mechanics Condylar and Fossa Cartilages Cells Extracellular matrix Tissue mechanics Mandibular Condyle and Temporal Fossa Pathology of the TMJ Current Therapies Tissue Engineering TMJ Disc Cell sources Scaffolds Bioactive agents Mechanical stimulation Condylar Cartilage Cell sources Scaffolds Bioactive agents Mandibular Condyle Cell sources Scaffolds Bioactive agents Future Directions for TMJ Tissue Engineering Progenitor Cells Mechanical Stimuli Other TMJ Tissues Disc attachments Joint capsule Conclusions References Relevant Websites science_18 Endocultivation: Computer Designed, Autologous, Vascularized Bone Grafts Glossary Introduction Endocultivation of Autologous Vascularized Bone Grafts The Living Bioreactor (Musculus Latissimus Dorsi) Clinical Applications of Endocultivation: Tissue Engineering of Autologous Customized Vascularized Bone Replacements Operative Technique Step 1: Preoperative planning and CAD design Step 2: Scaffold preparation and implantation Step 3: Transplantation Step 4: Mechanical loading and functional integration Clinical Results Future Improvements Summary References science_19 Biomaterials Selection for Dental Pulp Regeneration Glossary Abbreviations Introduction Biomaterial Selections Polymer Choices Scaffolding In Vivo Dental Pulp Regeneration: State of the Art Conclusions References science_20 Bioactive Ceramics and Bioactive Ceramic Composite-Based Scaffolds Glossary Abbreviations Introduction Limitations of Natural Bone Grafts Synthetic Bone Grafts and Materials Used Scaffold Requirements Load-Bearing Properties Degradation and Resorption Kinetics Scaffold Architecture for Bone Ingrowth and Permeability of Nutrients and Neovascularization Fundamentals of Ceramic Bioactivity Surface Transformation Protein Adsorption onto the Biomineralized Surface and Selective Binding of Integrins Characteristics of Bioactive Ceramics and Bioactive Ceramic Composite-Based Scaffolds for Bone Tissue-Engineering Sc Bioceramics and Bioactive Glasses Bioactive glasses and glass ceramics Compositions and bioactivity Mechanical properties Calcium phosphates Calcium phosphates composition and bioactivity Mechanical properties Ceramic/Polymer Composite Materials Composite materials strategy PLA/PGA-based polymer/ceramic composites Protein-based polymer/ceramic composites Modifications of Bioactive Ceramics and Bioactive Ceramic Composite-Based Scaffolds Localized Delivery of Biomolecules and Cells Conclusion and Future Directions References science_21 Calcium Phosphates and Bone Induction Glossary Abbreviations Bone and Its Biology Bone Grafting and the Strategies Bone Grafts Synthetic Bone Biomaterials Growth factors Bone tissue engineering Biomaterials for Bone Substitution From Bioinert Materials to Bioactive (Osteoconductive) Materials From Bioactive (Osteoconductive) Materials to Materials Associated with Osteoinduction Bone Induction Associated with Materials Bone Induction Study Models Bone Induction in the Presence of Calcium Phosphate-Based Ceramic Materials Phenomenon Animal dependence Bone formation and osteoinduction in the presence of materials Bone Induction by Non-CaP Materials Role of Calcium Phosphate in Bone Induction Material Factors Chemistry Microstructures Macrostructures Mechanism of Bone Induction Protein Adsorption Topography Surface Calcification Inflammation Clinical Significance of Osteoinductive Materials Repairing Small Bone Defects Critical-Sized Defects Spinal Fusion Future Directions References science_22 Bone Tissue Engineering: Growth Factors and Cytokines Abbreviations Bone Biology Introduction Fundamental Process Bone Morphogenesis Bone Modeling and Remodeling Angiogenesis Osteoblasts Osteocytes Osteoclasts Growth Factors, Cytokines, Nomenclature, Mechanism of Action Bone Tissue Engineering: Growth Factors and Cytokines Transforming Growth Factor beta Bone Morphogenetic Proteins Insulin-Like Growth Factors Platelet-Derived Growth Factor Vascular Endothelial Growth Factor Fibroblast Growth Factors Sclerostin Cytokines and Bone Receptor Activator of Nuclear Factor kappabeta Ligand IL1beta and TNF (Superfamily Member 2, TNF Alias TNF-α) Bone Resorption Osteoclast precursor signaling Osteoclastogenesis RANKL upregulation RANKL downregulation RANK expression Upregulation of osteoclastogenesis Downregulation of osteoclastogenesis Bone Formation Translational Applications of Growth Factors and Cytokines in Bone Tissue Engineering Dental Therapeutic bone regeneration in dentistry Orthopedic and Craniomaxillofacial Contextualizing the discussion Interpreting preclinical data Host factors Strategies for growth factor delivery Growth factors and cytokines in clinical use Nonrecombinant sources of growth factor and cytokines Recombinant sources of growth factor and cytokines Clinical applications: Recombinant human BMP-2 Recombinant human BMP-7 Future Clinical Directions Defining the clinical performance criteria References science_23 Carbon Nanotubes: Applications for In Situ Implant Sensors Glossary Abbreviations Introduction Making Orthopedic Implant Sensors Step 1: Preparation of Nanotubular Anodized Titanium Step 2: Cobalt-Catalyzed CVD for Growing MWCNTs Biological Responses to Orthopedic Implant Sensors Sensing Ability of Orthopedic Implant Sensors Discussion Conclusions Acknowledgment References science_24 Biomaterials for Replacement and Repair of the Meniscus and Annulus Fibrosus Glossary Abbreviations Overview Introduction Structure and Function of the Knee Meniscus Structure and Function of the AF Current Clinical Treatments for Damage to or Degeneration of the Meniscus and AF Current Meniscus Repair Methods Current AF Repair Methods Current Products for Meniscus and AF Repair and Replacement Current Products for Meniscus Repair Current Products for AF Repair Emerging Products for Meniscus and AF Repair and Replacement: Tissue Engineering Recent Developments in Meniscus Tissue Engineering Recent Developments in Disc Tissue Engineering Engineering Fiber-Reinforced Tissues with Nanofibrous Scaffolds Electrospinning: The Base Technology Engineering the Meniscus with Nanofibrous Scaffolds Engineering the AF with Nanofibrous Scaffolds Preclinical Models and Evaluation Tools for Engineered AF and Meniscus Products Conclusions and Future Directions Acknowledgment References science_25 Tissue Engineering Approaches to Regeneration of Anterior Cruciate Ligament Abbreviations Introduction Structure and Function of the ACL Limitations in Traditional Implantable Solutions A New Option: Tissue Engineering Biomaterials for Ligament Tissue Engineering Synthetic Biomaterials Natural Biomaterials Silk Biomaterials Scaffold Design Scaffolds Design Criteria Braided Scaffolds Knitted Scaffolds Cell Source Bioreactor System Local Delivery of Growth Factors Animal Models for ACL Regeneration Ligament-Bone Interface Summary Acknowledgment References science_26 Tissue Engineering of Muscle Tissue Glossary Introduction Importance of Skeletal Muscle Tissue Engineering Muscle Development and Repair Scaffolding Materials Hydrogels Synthetic Materials Natural Materials Collagen Fibrin Hyaluronic Acid Alginate Chitosan Matrigel Hydrogels for Vascularization Additions to Current Matrices Vascularization Innervation Alternative Cell Types for Skeletal Muscle Engineering Electrical and Mechanical Stimulation of Skeletal Muscle Matrix Metalloproteinases Immune Response to Engineered Muscle The Aged Niche Pathological Environment Future Directions Culturing Satellite Cells Genomics, Proteomics, and Metabolomics References science_27 Cardiovascular Tissue Engineering Glossary Abbreviations Introduction Bench Top to Bedside Successful Tissue Engineering Translations Cardiac Patches Direct Injection Versus Tissues Constructs Biomaterials for Cardiac Tissue Engineering Scaffold-based systems Hydrogels Cellular sheet structures Limitations of cardiac constructs Cell Delivery Using Biomaterials Hydrogels Nanofibers ECM Proteins Synthetic Polymer Scaffolds Tissue Engineering of Artificial Vesseles The Evolution of Tissue-Engineered Blood Vessels Biodegradable Scaffolds A Cell-Synthesized Scaffold Elastin as a Natural Scaffold Mechanical Testing Size and Scope of the Peripheral Market Market size and growth Tissue Engineering of Heart Valves Classic Mechanical and Biological Heart Valves Device Challenges Tissue-Engineered Heart Valves Regeneration versus repopulation Biomaterials used for heart valves References Relevant Websites science_28 Tissue Engineering of Heart Valves Glossary The Ideal Valvular Substitute Heart Valve Disease and State of the Art The `Gold Standard´: Architecture of Native Heart Valves Requirements for the Ideal Valvular Substitute Strategies in Autologous Heart Valve Tissue Engineering In Vitro Heart Valve Tissue Engineering Principal Strategies Scaffold Materials Native, decellularized biological matrices Polymeric starter matrices Aliphatic polyesters Polyhydroxyalcanoates Biological/polymeric hybrid starter matrices Collagen-based scaffolds Fibrin-based scaffolds From animal to human: in vivo performance of tissue-engineered heart valves In Vitro Heart Valve Tissue Formation Bioreactors for Heart Valve Tissue Engineering: Design and Function In Vivo Heart Valve Tissue Engineering Principal Strategies Native, Decellularized Scaffold Materials Synthetic Scaffolds Materials The `Biovalve´ Concept: The Patient as a Perfect Bioreactor? The In Vivo Tissue Engineering Approach: Significance of a Novel Concept Cell Sources for Heart Valve Tissue Engineering Cardiovascular-Derived Cells Bone Marrow-Derived Cells Blood-Derived Cells Umbilical Cord-Derived Cells Prenatally Harvested Progenitor Cells Adipose Tissue-Derived Cells Toward Clinical Application - Outlook for the Future References science_29 Biomaterials for Cardiac Cell Transplantation Abbreviations Introduction Biomaterial Design Requirements for Cardiac Cell Transplantation Three-Dimensional Scaffold Biological Cues: Cells Communicate with the ECM Through Cell-Surface Receptors Mechanical Properties Oxygen Transport Electromechanical Coupling Current Materials Naturally Derived Materials as Scaffolds Collagen Alginate Fibrin Chitosan Hyaluronic acid Synthetic Biomaterials as Scaffolds Poly(glycolide) and poly(lactide) PEG-based hydrogels Poly(N-isopropylacrylamide) Hybrid Biosynthetic Materials Smart biomaterials: growth factors and self-assembling peptides Concluding Remarks References science_30 Medical Applications of Cell Sheet Engineering Glossary Abbreviations Introduction Cell Sheet Engineering Organized Combination of the Structure and Function of Cell Sheet Gap Junctions and Cell Sheet Engineering Functional Tissue Engineering with Cell Sheets Electrical Coupling Between Layered Cardiomyocyte Sheets 3-D Manipulation of Cardiomyocyte Sheets Production of Multilayer Myoblast Sheet Constructs In Vitro Clinical Application of Cell Sheet Tissue Engineering Heart Failure Therapy by Using Cell Sheet Engineering Conclusions Acknowledgment References Relevant Websites science_31 Peripheral Nerve Regeneration Abbreviations Introduction Anatomy and Physiology of the Nervous System Peripheral Nerve Injury: Degeneration and Regeneration Current Approaches to Bridging Nerve Gaps Physical Versus Biological Contributors to Peripheral Nerve Repair Biological Grafts and Synthetic Nerve Guidance Conduits Biological-based grafts Biomaterials and tissue engineered nerve guidance conduits Filler materials for nerve guidance conduits Scaffold Fabrication Strategies The Use of Bioactive Biomolecules Role of Schwann cells in the Peripheral Nerve Regeneration Process Stem Cells for Peripheral Nerve Regeneration Concluding Statements References science_32 Nerve Tissue Engineering Glossary Abbreviations Introduction Why Nerve Tissue Engineering? Social Impact of Nerve Injuries PNS and CNS: Structures and Physiological Responses to Injury Peripheral nervous system Central nervous system State of the Art of PNS Tissue Engineering Entubulation Technique and Nerve Conduit Design (see Chapter 00183) Overview of Ongoing Research and Potential for Therapeutic Use Case Study: Collagen-Based Tubes with Oriented Porous Patterns State of the Art of CNS Tissue Engineering (see Chapter 00185 and Chapter 00238)) Cellular Strategies Molecular Strategies Biomaterial-Based Strategies (see Chapter 00185 and Chapter 00238) From Biomaterials to Tissue-Engineered Devices: Combinatorial Strategies Concluding Remarks References Relevant Websites science_33 Biomaterials for Central Nervous System Regeneration Glossary Introduction Biomaterial Therapy Options Drug Delivery Introduction Systemic delivery systems Liposomes Polymeric nanoparticles Local delivery systems Scaffolds for CNS Repair Introduction Characteristics of scaffolds in CNS Nerve Channels Introduction Characteristics of nerve channels Spinal Cord Injury Introduction Scaffolds in SCI Drug Delivery and Nerve Channels in SCI Alzheimer's Disease Introduction Biomaterial Therapies for Alzheimer's Parkinson's Overview of Parkinson's Biomaterials in Treatment for Parkinson's Disease Biomaterials Used with Stem Cell Therapy Stem Cell Use in CNS Injury Biomaterials and Stem Cells Summary of Biomaterial Therapies in CNS Injury/Disease References science_34 Skin Tissue Engineering Abbreviations Skin Anatomy and Function Basic Anatomy and Function of the Skin Epidermis Structure and cell constituents of epidermis Functions of epidermis Dermal-Epidermal Junction Dermis Structure and cell constituents of dermis Functions of the dermis Hypodermis (Subcutaneous Fat Layer) Biology of Cutaneous Wound Healing Inflammatory Phase Tissue Formation Phase Remodeling Phase Interruption of Wound Healing Wound Classifications and Prognosis The Significance of Tissue-Engineered Skin Application Design Principles of Tissue-Engineered Skin Substitute Materials for Skin Tissue Engineering Development of Nonbiodegradable Synthetic Materials Development of Biodegradable Natural-Based Materials Collagen Fibronectin Fibrin Hyaluronic acid Development of Smart Matrix: New Concept for Biodegradable Synthetic Biomaterials The Development of Tissue-Engineered Skin Constructs: The Past and the Present Status Overview Epidermal Skin Substitutes Epicel and EpiDex Laserskin Bioseed-S MySkin ReCell/CellSpray Dermal Skin Substitutes Collagen-based dermal analogs: AlloDerm, GraftJacket, Karoderm, SureDerm, Permacol Surgical Implant, and Matride Collagen-based sponge: Pelnac, Terudermis Collagen-based composites: Integra, Biobrane, TransCyte Dermagraft OASIS Wound Matrix EZ Derm Hyalomatrix PA, Hyalograft 3D Dermo-epidermal (composite) Skin Substitutes Karoskin Apligraf OrCel TISSUETech Autograft system Problems and Challenges of Available Skin Substitutes Biocompatbility Physical Properties Limited Vascularization and Poor Engraftment into Wound Site Scarring Others Divine Garments Without Seams (Ancient Chinese Proverb): The Inspiration for Tissue-Engineered Skin Substitute from Mammalian External Ear: Examples of Regeneration in Adult Animal Rabbit ear MRL/MpJ mouse ear Mammalian Skin Hair Follicle: Examples of Regeneration in Adult Animal Embryonic Skin: Examples of Scarfree Regeneration in Fetal Animal Inspiration from Mammalian External Ear and Fetal Skin Regeneration Stem cells: cell-based regeneration strategy Vascularization: sustaining pipelines to construct the skin substitutes Incorporation of bioactive molecules in the design of an intelligent skin substitute Smart scaffold/matrix: structural determinant biological activity Conclusions Acknowledgment References science_35 Cartilage Regeneration in Reconstructive Surgery Glossary Abbreviations Introduction Role of Tissue Engineering Cell Sources and Materials Cells Materials Characterization of Scaffolds In Vitro and In Vivo In Vitro Model Using a Thermoreversible Polymer In Vitro Model Using a Biodegradable Polymer Autologous In Vivo Model Using a Thermoreversible Polymer Autologous In Vivo Model Using a Biodegradable Polymer Conclusions References science_36 Tissue-Engineering Hollow Noncardiac Intrathoracic Organs: State-of-the-Art 2010 Glossary Abbreviations Introduction Historical Background Alloplastic Tracheal Transplantation: Solid Prostheses Alloplastic Tracheal Transplantation: Porous Prostheses Tracheal Reconstruction with Autogenous Tissues Nonviable Cadaveric Human Tracheal Allograft Transplantation Viable Tracheal and Laryngeal Allograft Transplantation Tissue-Engineered Trachea: Basic Sciences to Clinical Application and Transplantation Suitable Scaffolds (Natural, Synthetic) Decellularized, Nonimmunogenic Matrices (Allogenic, Xenogenic) Seeding with Stem Cells Bioreactors Transplantation in Animal Models and Humans Tissue-Engineered Larynx for Total Laryngeal Replacement and Transplantation: The Ultimate Goal Generation of Muscle Reinnervation Revascularization Immunogenicity Future Challenges and Goals Tissue Engineering the Esophagus: A Preliminary Step Toward Generating a Tissue-Engineered Larynx Conclusions References science_37 Adipose Tissue Engineering Glossary Abbreviations Introduction Adipose Tissue Engineering Adipose Tissue Structure and Function Cellular Composition Adipogenesis Secretory Function of Adipose Tissue Adipose-Derived Stem Cells Biomaterials for Adipose Tissue Engineering Natural Biomaterials Alginate Chitosan Collagen and gelatin Fibrin Hyaluronic acid Matrigel Other naturally derived materials Synthetic Biomaterials Biodegradable polymers Future Outlook References Relevant Websites science_38 Finger Abbreviations Introduction Periosteum for Human Phalanx Model In Vivo Model for Phalanx Biomaterials Techniques for Fabrication Preparation of the phalanx Preparation of the joint cartilage Preparation of the human phalanx model in vitro In vivo implantation of the human phalanx model Development of the Human Phalanx Model Gross Morphology X-Ray Findings Histology Assessment of the Human Phalanx Model Mechanism of Ossification Osteogenic Capability of the Copolymer Signal Pathway Between Periosteum and Joint Cartilage Conclusion and Future Directions References science_39 From Tissue to Organ Engineering Glossary Abbreviations Introduction Biomaterials Naturally Derived Materials Acellular Tissue Matrices Synthetic Polymers Cells for Use in Tissue Engineering Embryonic Stem Cells Laboratory-Generated Stem Cells Amniotic Fluid and Placental Stem Cells Adult Stem Cells and Native Progenitor Cells Cell Therapy with Injectable Substances Bulking Agents Injectable Muscle Cells Endocrine Replacement Tissue Engineering of Specific Structures Urethra Bladder Kidney Male Reproductive Organs Female Reproductive Organs Blood Vessels Heart Liver Articular Cartilage and Trachea Summary and Conclusion Acknowledgment References science_40 Kidney Tissue Engineering Glossary Introduction Developmental Techniques Renal Progenitor Cells Cellular-Based Therapies Stem Cells for Use in Renal Tissue Regeneration ES Cells Single-cell embryo biopsy Obtaining cells from arrested embryos Therapeutic cloning (SCNT) Altered nuclear transfer Reprogramming (iPS Cells) Amniotic-Fluid and Placenta-Derived Stem Cells Adult Stem Cells In Situ Kidney Development Renal Tubular Assist Devices Summary and Conclusions Acknowledgment References science_41 Liver Tissue Engineering Glossary Abbreviations Introduction Liver Structure and Function Liver Failure Strategies for Replacement of Hepatic Function Extracorporeal Liver Support Devices Bioreactor Design Cell Source Implantable Hepatic Support Systems Direct Cell Transplantation Microcarrier and Encapsulated Systems Polymer Scaffolds Microfabrication for Liver Tissue Whole Liver Tissue Engineering Conclusions and Future Directions References science_42 Organ Printing Abbreviations Introduction Novel Scaffold Fabrication Methods in Tissue Engineering Organ Printing Rationale for developing organ-printing techniques 2D Patterning and Cell Printing Introduction State of the Art Techniques for patterning cell culture substrates Examples of 2D substrate patterning studies for tissue engineering Direct manipulation of cells Translating 2D Approaches to 3D 3D Organ-Printing Processes Organ Printing Versus Book Printing Overview of 3D Techniques Inkjet printing Robotic dispensing systems Stereolithography Robotic assembly Developmental Phases and Components Associated with 3D Organ Printing Preprocessing: design Printing cell-laden 3D hydrogel constructs Hydrogels: gels used and criteria for developing hydrogel carriers for cell and organ printing Scaffold-free assembly: aggregates and cell-sheets Printing of multiple cell populations and tissue equivalents Postprocessing Future Directions Current Limitations in Organ Printing Scale of Application Tissue Complexity and Vascularization Conclusions References Volume 6 Biomaterials and Clinical Use science Current and Projected Utilization of Total Joint Replacements Glossary Abbreviations Introduction International Total Hip and Knee Implant Registries Public Data Sources for Orthopedic Implant Utilization in the United States National Hospital Discharge Survey Nationwide Inpatient Sample Medicare Current Utilization of Total Joint Replacements Projected Utilization of Total Joint Replacements Summary References Relevant Websites science_2 Bone Cement Glossary Abbreviations Symbols Introduction Bone Cement Chemistry Bone Cement Applications Bone Cement in Surgery Potential Adverse Effects of Bone Cement Bone Cement as an Antibiotic Delivery System Mechanical Properties of PMMA-Bone Cement Overview Properties in the Nonsolid Phase Viscosity Structure of Solid Bone Cement Overall composition Molecular weight Porosity Radiopacifiers Properties in the Solid Phase Overview Static compressive properties Static tensile properties Shear strength Creep Fracture toughness Fatigue fracture Effect of environment, differences between industrial PMMA and bone cement, and BaSO4 addition... Porosity reduction Effects of notches and surface irregularities Porosity reduction: how does it work? Failure mechanisms Summary Improving PMMA-Bone Cement Introduction Chemical (`or Internal´) Modifications Fiber Reinforcement Summary and Concluding Remarks References science_3 Ultrahigh Molecular Weight Polyethylene Total Joint Implants Abbreviations Symbols Introduction General Properties and Processing of UHMWPE Manufacture Structure-Property Relationships The Effects of Sterilization and Early Developments Cross-linking Technologies Early Experience with Cross-linking Radiation Cross-linking Followed by Thermal Treatment Formation of cross-links and wear reduction through cross-linking The effects of thermal treatment during or after irradiation on oxidation and wear Development of highly cross-linked total knees Mechanical and fatigue properties Sequential Irradiation and Annealing Vitamin E-Stabilized, Radiation Cross-linked UHMWPE The Rationale and Incorporation Methods Mechanism of Action Against Oxidation Diffusion of Vitamin E in UHMWPE Oxidative Properties Wear Peri-Prosthetic Effects Mechanical and Fatigue Properties Other UHMWPEs with Clinical Potential High-Pressure Crystallized UHMWPE with Stabilized Free Radicals Vitamin E-Blended, Irradiated, and Mechanically Annealed UHMWPE Surface Cross-linked UHMWPE Conclusions and Future Directions References science_4 Ceramic Prostheses: Clinical Results Worldwide Abbreviations Introduction History Early Clinical Results Evolution of the Mechanical Properties of Alumina and the New Alumina Matrix Composite Proven Long-Term Clinical Stability Biocompatibility Current Manufacturing State of the Art Ceramic Component Failure Recent Clinical Reports of the Use of the Latest Generation of Alumina Ceramics United States Experience European Experience Asian Experience Statistical Observations of the Largest Ceramic Manufacturer Clinical Report Database (January 2000 to September 20 Ceramic Component Squeaking The Beneficial Wear Properties of Alumina Ceramics Outweigh the Risk of Fracture Clinical Use of Ceramics in the Global Community Ceramics Allow Large Diameter Wear Couple with Little Wear Debris Conclusions References Relevant Websites science_5 Porous Coatings in Orthopedics Abbreviations Introduction Objectives of Joint Replacement Objectives of Biological Fixation Using Porous Materials Materials Used for Porous Coatings Metals Cobalt-based alloys Titanium-based materials Tantalum Ceramics and Ceramic-Coated Metals Polymers Properties of Porous-Coated Implants Mechanical Properties Electrochemical Properties Design and Characterization of Porous Materials Porous Coatings in Tissue Engineering Summary and Future Directions References science_6 Biological Effects of Wear Debris from Joint Arthroplasties Glossary Abbreviations Introduction Orthopedic Wear Debris Biologic Reactions of the Host to Wear Debris Macrophages Osteoblasts and MSCs Osteoclasts Other Factors Modulating the Biological Activity of Wear Particles Genetic Contribution Endotoxin Implant Instability Pressure New In Vivo Models and Development of Particle-Induced Osteolysis Models of Continuous Delivery of Particles In Vivo Cell Trafficking in the Presence of Wear Particles Therapeutic Strategies Conclusion Acknowledgment References science_7 Fretting Corrosion of Orthopedic Implants Abbreviations Introduction Orthopedic Alloys Stainless steel alloys Cobalt-chromium alloys Titanium alloys Implant Junctions Screw-plate interface Modular junctions Experimental Methods: Implant Fretting Corrosion Methods: Oxide Layer Testing Methods: Modular Junction Fretting Testing Open circuit potential Metal release fretting corrosion testing Mechanical loading Short-term testing Long-term testing Implant Fretting and Biocompatibility Past Investigation of Fretting Corrosion Testing Conclusions References science_8 Implant Debris: Clinical Data and Relevance Abbreviations Introduction Implant Debris Types: Particles and Ions Particulate Debris Particle characterization Metal Ions (Soluble Debris) Metal ion release Local Tissue Effects of Wear and Corrosion Systemic Effects of Wear and Corrosion Systemic Particle Distribution Hypersensitivity Incidence of hypersensitivity responses among patients with metal implants Testing for metal sensitivity Carcinogenesis Conclusions References science_9 Orthopedic Implant Use and Infection Abbreviations Orthopedic Implants New-Generation Biomaterials Orthopedic Complications Periprosthetic Infection Prevalence and Etiology Mechanisms and Routes of Infection Biofilms in Pathogenesis of Infection Biofilms and Multidrug Resistance The Diagnostic Dilemmas Markers of Infection Microbiology Assays Intraoperative Diagnosis An Interjection on Orthopedic Trauma Classification Schemes for Implant Infection Management of Periprosthetic Infection Surgical Approaches Antibiotic-Laden Bone Cements Self-Protective Implants The Future of Implant Design in Orthopedic Infection Nanomolecular Permanent Modification of Biomaterials Feasibility of the Concept Conclusions References science_10 Trends in Materials for Spine Surgery Glossary Abbreviations Introduction Anatomy and Physiology of the Spine The Vertebral Column The Intervertebral Disc The Nucleus Pulposus The Annulus Fibrosus Intervertebral Disc Degeneration Spinal Fusion Metals for Spinal Cages and Interbody Spacers Polymers and Composites for Fusion Cages Wires, Tapes, and Cables in Spinal Fusion Pedicle Screws, Plates, Bands, and Rods for Fusion and Dynamic Stabilization Bioresorbable Materials for Spinal Fusion Implants Total Disc Arthroplasty Material Requirements Implant endplate Bone implant interface Bearing surfaces General material specifications Discontinued Artificial Discs Acroflex First generation Second generation Third generation Currently Available Devices Charitè artificial disc SB Charitè I and II SB Charitè III ProDisc Maverick Flexicore Future Trends Annulus Repair Procedure Mechanical Role Reported Treatment Methods Suture techniques Sealant and bulking techniques Current Technologies Xclose tissue repair system Material Procedure Barrier Technologies Inclose surgical mesh system Materials Procedure Studies on the device Barricaid prosthesis Material Procedure Studies on the device SpineJet XL Material Requirements Future Trends Concluding Remarks References science_11 Injectable Bone Cements for Spinal Column Augmentation: Materials for Kyphoplasty/Vertebroplasty Abbreviations Introduction History of Spinal Column Augmentation with Injectable Bone Cements and Currently Accepted Indications... History Currently Accepted Indications Painful osteoporotic vertebral compression fractures Painful metastatic/malignant vertebral body lesions Traumatic fractures Overview of Frequently Used Injectable Bone Cements for Spinal Augmentation Acrylate Cements Mixing phase Initial propagation phase Injection phase Curing phase CaP Cements Composite Cements (Hybrid Acrylic/CaP Cements) Miscellaneous Cements Clinical Results of Spinal Column Augmentation with Injectable Bone Cements Osteoporotic Vertebral Compression Fractures Metastatic/Malignant Vertebral Body Lesions Traumatic Fractures Complications in Spinal Column Augmentation Fracture Type Duration of Symptoms Instruments/Instrument Positioning/Spinal Anatomy Viscosity of Cement Injected Volume of Cement Injected Mechanical/Thrombogenic/Thermal Properties of Cement General Patient Health Characteristics Future Directions and Conclusions References science_12 Biomaterials for Intervertebral Disc Regeneration Glossary Abbreviations Overview of Intervertebral Repair: Current Strategies Introduction Normal Disc Structure and Function: Disc Cells, Extracellular Matrix, Nutrition Aging and Degeneration: Pathophysiology, Effect on Function and Pain, Repair Capacity Current Treatment Options (Conservative, Fusion Surgery, Motion Preservation Techniques, and Devices)... New Treatment Strategies in Research (Protein Injections, Gene Therapy, Cell Therapy) Repair of the NP The Pathobiology of the NP Current Therapeutic Strategies Candidate Biomaterials for Nucleus Repair Polymers and biological molecules Biomaterials for tissue-engineering methods in cell-based nucleus repair Overview of Nucleus Repair and Regeneration Biomaterials for Cell Scaffolds Future Perspectives Repair for the AF Development and Healthy Structure of the AF Surgical Strategies to Rescue the AF Nonbiodegradable Materials Biodegradable: Resorbable Materials Polymers Silk and other biomaterials Collagen fiber scaffolds (electrospinning) Future Perspective: The Biological AF Replacement References science_13 Nucleus Replacement Abbreviations Introduction Intervertebral Disk Microbiology of the intervertebral disk Biomechanics Principle planes/rotations Evaluation of spinal motion Viscoelastic properties Ageing and Disk Injury Degenerative Disk Disease Causes of DDD Morphologic changes Biomechanical changes Microbiological changes Pain Herniation Causes Morphological/radiographic/soft tissue changes Changes in motion Microbiological changes Pain Treatment Options Conservative Treatment Discectomy Surgical procedure Outcome Radical versus limited discectomy Total Disk Arthroplasty Surgical technique Fusion Nucleus Replacement Solid Preformed Implants Preformed Hydrogel Implants Externally Inflated Implants Injectable Implants Scaffolds, Cells, Growth Factors, and Tissue Engineering Concepts Considerations for Evaluating Nucleus Replacements In Vitro and In Vivo In Vitro Evaluation of Nucleus Replacement Performance Hydration/temperature Repeated testing In Vivo Studies: Animal Models Murine Leporine Porcine Canine Bovine Ovine Nonhuman primates Summary - animal models Summary References science_14 Wear: Total Intervertebral Disc Prostheses Glossary Abbreviations Introduction to Total Disc Prostheses Back and Neck Pain Degenerative Disc Disease and TDR Basic Anatomy and Biomechanics of the Spine The Spine The Natural Disc and Associated Structures The FSU and Spine Biomechanics Cervical spine loading Lumbar spine loading Cervical spine motions Lumbar spine motions Shear loads and motions Instantaneous axis of rotation The Degenerated Disc and Associated Structures TDR Surgery Indications and Contraindications Access/Surgical Techniques Success Complications Revision TDR Design History and Evolution Material Selection Constraint Evidence of TDR Wear TDR Wear Simulation ISO and ASTM Standards Spine Wear Simulators Wear Simulation Validation Wear of Metal-PE TDR Wear of Metal-Metal TDR Wear of Alternative Material TDR Biological Response to TDR Wear Debris Biological Response to PE Debris in the Spine Biological Response to Metal Debris in the Spine Conclusions References Relevant Websites science_15 Intervertebral Disc Glossary Abbreviations Background Spinal Fusion Bone grafts Synthetic bone grafts Demineralized bone matrix Growth factors and gene therapy Motion Preservation Total disc replacement Dynamic stabilization IVD transplantation Regenerative medicine and tissue engineering approaches to motion preservation IVD Structure and Function Extracellular Matrix Organization IVD Preservation, Repair, and Regeneration Nuclear Replacement Acellular Cellular Annular Repair Acellular Cellular Total Disc Replacement Future Challenges References science_16 Materials in Fracture Fixation Abbreviations Fracture Healing Biological Requirements for Fracture Healing Mechanical Requirements for Fracture Healing Basic Requirements of Biomaterials for Fracture Fixation Device Biocompatibility Corrosion Resistance Mechanical Properties Devices Used in Fracture Fixation Plate and Screw Fixation Design rationale Applications of biomaterials to plate and screw fixation Advantages of plate and screw fixation Limitations of plate and screw fixation Intramedullary Fixation Design rationale The application of biomaterials in internal fixation Advantages of intramedullary fixation Limitations of intramedullary fixation External Fixation Design rationale The application of biomaterials in external fixation Advantages of external fixation Limitations of external fixation Structural Augmentation Calcium phosphate ceramics Calcium phosphate cements Hydroxyapatite Tricalcium phosphate Glass ceramics Polymers Composites References science_17 Bone Tissue Grafting and Tissue Engineering Concepts Glossary Introduction Historical Overview Ceramics and Glasses Calcium phosphates Calcium sulfate Bioactive glass Physical parameters of ceramics and bioactive glasses Polymers Polymeric Bone Graft Substitutes to Tissue Engineering Bone Tissue Engineering Tailoring Biomaterials for New Age Bone Grafts Anatomically specific shape and architecture Mechanical properties Degradation Surface chemistry and topographical cues Cellular adhesion New Age Bone Graft Approaches Implanting in vitro cultured tissues Delivering MSCs Osteoconduction Osteoinduction Animal Models for Assessing Effectiveness of Bone Tissue Engineering Strategies Calvarial Defects Maxillary Sinus Augmentation Analysis Methods for Cranial Defects Critical-Sized Segmental Defect References science_18 Materials in Tendon and Ligament Repair Glossary Abbreviations Introduction Basic Properties of Tendon and Ligament Classification General Structure Composition Biomechanical Properties Effect of Mechanical Loading Tendon and Ligament Injury and Healing Summary Augmentation of Scaffolds Animal Models in Tendon and Ligament Research Choosing an Appropriate Animal Model Animal Models of Tendon Injury Animal Models of Ligament Injury Graft Materials Biologic Materials Collagen derivatives Polysaccharides: Chitin, chitosan, alignate, and hyaluronan Silk Xenograft Small intestinal submucosa Dermis Autograft/allograft Synthetic Materials Resorbable polyesters Polyglycolic acid Polylactic acid Polylactic-co-glycolic acid Poly(caprolactone) Summary and general observations in polyesters Nonresorbable materials Carbon Polyethylene terephthalate Polytetrafluoroethylene Clinical Application Rotator Cuff Anterior Cruciate Ligament Suture Anchors Summary References Relevant Websites science_19 Materials in Dental Implantology Glossary History and Development of Dental Implantology Indication and Procedure for Dental Implants Functional Goal of Dental Implants Typical Indications Edentulous jaws Fixed partial denture Special indications Implant survival and success criteria General and Local Risk Factors Surgical Procedure Presurgical considerations Surgery Tissue Reaction on Dental Implant Material Bone (Enossal Part) Early interaction with noncellular components of the extracellular milieu Platelet activation and cytokine release Inflammation period, chemotaxis Osteoconduction and matrix synthesis, functional remodeling Soft Tissue (Mucosa and Epithelium) Experimental Methods Mechanical testing and modeling Cell culture methods Animal models Human histology Implant Materials Metal Ceramics Surface Structure and Modifications Macrostructure Physical Modification (Roughness) Chemical Modifications Clinical Impact of Surface Modifications Biofilm and Peri-implantitis Biofunctionalization Implant Design Principles in the Endosseal Part Future Developments References Relevant Websites science_20 Dental Graft Materials Abbreviations Introduction Categories of Dental Grafting Materials Hydroxyapatites TCP Ceramics Bioactive Glass 45S5 Calcium Carbonate Biphasic HA TCP Materials Demineralized Freeze-Dried Bone Allografts and Mineralized Freeze-Dried Bone Allografts Polymer-Based Scaffolds for Craniofacial Tissue Engineering Bone Grafting Cements Combination of Bone Grafting Materials with Platelet-Rich Plasma Combined Use of Grafting Materials and Growth Factors or Other Biologicals Growth factors Enamel matrix derivative Requirements and Novel Developments for Dental Graft Materials Requirements for Dental Graft Materials Novel Developments for Dental Graft Materials Calcium alkali orthophosphate materials The effect of calcium-alkali-orthophosphate ceramics on the expression of the osteoblastic phenotype in vitro... The effect of calcium alkali orthophosphates on bone formation and osteoblastic phenotype expression in vivo... The effect of calcium alkali orthophosphate ceramics on cell adhesion and intracellular signaling mechanisms... The effect of calcium alkali orthophosphate-based bone substitute cements on bone formation and osteogenic marke The effect of beta-TCP particles with varying porosity on osteogenesis after sinus floor augmentation in humans. Three-dimensional calcium-alkali-phosphate-based scaffolds for bone tissue engineering Summary Acknowledgment References science_21 Biomaterials and Their Application in Craniomaxillofacial Surgery Abbreviations Introduction Biomaterials and Implants in Craniomaxillofacial Surgery Skeletal Fixation/Stabilization Metals and alloys Resorbable polymers Clinical application External fixation Open reduction internal fixation Extracellular matrix and growth factor-coated implants Skeletal Replacement and Augmentation Methyl methacrylate Silicone implants Hard tissue replacement (HTR) Porous polyethylene (MEDPORTM) Hydroxyapatite and bioactive glass Demineralized bone Cartilage Replacement Soft Tissue Replacement and Augmentation Collagen Dermal substitutes Alloderm DermaMatrix Hyaluronic acid Polymethylmethacrylate Poly-l-lactic acid Calcium hydroxyapatite-based dermal filler Fat Expanded polytetrafluoroethylene implants High-density polyethylene implants Considerations and Future Applications References science_22 The Effect of Substrate Microtopography on Osseointegration of Titanium Implants Abbreviations Introduction In Vitro Studies Mechanisms Mediating the Microtopography Effect In Vivo Studies Summary Acknowledgment References science_23 Materials in Fixed Prosthodontics for Indirect Dental Restorations Glossary Abbreviations General Introduction Indirect Restorations Metallic Restorations Lost-wax casting Introduction Noble and precious metal alloys High-gold alloys Medium- and low-gold alloys Silver-palladium alloys Base metal alloys Cobalt-chromium alloys Titanium alloys Commercially pure titanium Titanium-6% Aluminum-4% Vanadium Spark erosion Grinding Three-axis grinding devices Four-axis grinding devices Five-axis grinding devices Selective laser melting Dental Ceramics Introduction Dental porcelains Processing of dental porcelains Compaction Firing Glazing Properties of dental porcelain Classification of modern dental ceramics Ceramo-Metals Introduction Choice of ceramo-metal alloys High-gold alloys Gold-palladium alloys High-palladium alloys Palladium-silver alloys Cobalt-chromium alloys Commercially pure titanium All-Ceramic Restorations: High-Strength Core Ceramics Introduction Core materials Silica-based ceramics Infiltration ceramics Pure alumina cores (see Chapter 00016) Zirconia core systems (see Chapter 00017) Drawback of high-strength core systems CAD-CAM in Dentistry Definition CAD-CAM concepts in dentistry Chair-side production Laboratory production Centralized production CAD-CAM components Scanner Design software Materials to be processed on dental CAD-CAM devices Metals Resin materials Silica-based ceramics Infiltration ceramics Oxide high-performance ceramics Processing Reflections References science_24 Cardiac Patch with Cells: Biological or Synthetic Abbreviations Native Myocardium: Unique Tissue Properties Anatomical Considerations Anisotropic Architecture of the Heart Coronary Blood Flow Electrophysiological Integration Physiologic Cellular and ECM Turnover Clinical Indications for Myocardial Patch Repair Congenital Malformations Atrial septal defect Ventricular septal defects and tetralogy of Fallot Hypoplastic left heart syndrome and functional single ventricle Acquired Heart Disease Coronary heart disease Dilatative myocardial dysfunction Other forms of cardiomyopathy Patch Materials in Current Clinical Use Autologous Pericardium Xenogenic and Decellularized Xenogenic Pericardium Synthetic Polymers Experimental Synthetic Polymers Strategies for Myocardial Tissue Engineering In Vitro Construction of 3D Structures with Cardiomyogenic Characteristics Commonly Used Cell Sources Solid or Gelling Scaffold Components: Some Considerations From Diffusion to Perfusion Controlled Stimulation by a Cellular Workout Program Pacing for a Better Cardiac Patch In Vivo Maturation of a Cardiac Patch Experimental Transmural Ventricular Replacement Experimental Ventricular Support by Patch Material Scientific Frontiers Clinical Relevance and Perspectives Summary References science_25 Long-Term Implantable Ventricular Assist Devices (VADs) and Total Artificial Hearts (TAHs) Abbreviations Introduction Evolution of VADs and TAHs Anatomical and Physiological Considerations Configuration LVAD Evolution First-Generation LVADs Rotary Axial Pumps Rotary Centrifugal Pumps Rotary centrifugal pumps using hydrodynamic suspension Rotary centrifugal pumps using full magnetic levitation Partial Circulatory Support VADs Total Artificial Heart Conclusions Acknowledgment References science_26 Cardiac Valves: Biologic and Synthetic Abbreviations Introduction Native Heart Valve Structure Current Treatments Ideal Scaffold Synthetic Scaffolds Decellularized Heart Valve Scaffolds Naturally Derived Biomaterials of Nonvalvular Origin Conclusion Acknowledgment References science_27 Drug-Eluting Stents Abbreviations Introduction The Need for Coronary Stents: Problems with Baloon Angioplasty and Bare-Metal Stents Development of DESs First Generation DESs Sirolimus-Eluting Stent Paclitaxel-Eluting Stent TAXUS express versus TAXUS liberté Benefits of DES Risks of DES Second Generation DES Zotarolimus-Eluting Stents Everolimus-Eluting Stent Second Generation DES Versus BMS Second Generation DES Versus First Generation DES Second Generation DES Versus Second Generation DES New Drug-Eluting Stents DES with Biodegradable Polymers Biolimus A9-eluting DES with biodegradable polymers Sirolimus-eluting DES with biodegradable polymers Paclitaxel-eluting DES with biodegradable polymers Polymer-Free DES BioFreedom biolimus A9-eluting stent VESTAsyn sirolimus-eluting stent YUKON: sirolimus-eluting stent DES Made from New Metal Alloys TAXUS element PROMUS element Nitinol Stents Lesions in small vessels Lesions in bifurcation Lesions due to vulnerable plaque Less Successful Medications on DES Conclusions References science_28 Vascular Grafts Glossary Abbreviations Introduction Materials Used for Vascular Grafts: Current Clinical Experience Autogenous Vein and Artery: The Gold Standard Material Veins Arteries Synthetic Grafts Expanded polytetrafluoroethylene Polyethylene terepthalate Endovascular surgery Host Responses to Implanted Biomaterials Host-Material Interfacial Processes Protein adsorption Platelet deposition Inflammation and immunology Endothelialization Mesenchymal cell infiltration Biomechanics Improving Clinical Outcomes and Future Concepts Systemic Pharmacotherapy Acetylsalicylic acid Clopidogrel Statins Warfarin Coating and Surface Modification Surface passivation Heparin-bonding Graft endothelialization Drug-eluting stents and graft Optimization of Biomechanical Biocompatibility Gene Therapy Tissue-Engineered Blood Vessels General Concepts Hydrogel-Based TEBVs Bioresorbable TEBVs Self-Assembled TEBVs Decellularized Vessel Scaffolds Final Remarks References science_29 Cerebrospinal Fluid Shunts Glossary Abbreviations Introduction Hydrocephalus Treatment of Hydrocephalus Shunting Early Shunts: Biomaterials and Biocompatibility The Next Stage State-of-the-Art Shunts Biocompatibility of Silicone Shunts Infective Complications Causative Bacteria Source of the Infecting Bacteria Incidence of Shunt Infection Treatment of Shunt Infections Biofilms and Other Reasons for Treatment Failure Treatment Regimens Prevention of Shunt Infections Surgical Technique Prophylactic Antibiotics Antimicrobial Shunt Catheters Principles of Antimicrobial Biomaterials for Shunting Coated Catheters Impregnated Catheters Biological Importance of the Boundary Layer Evaluation of Antimicrobial Catheters Broth Culture Test Roll Plate Test Zone Plate Test Serial Plate Transfer Test Time to Kill Assay In Vitro Challenge In Vivo Testing Application of In Vitro Tests to Existing Shunt and EVD catheters Hydrogel: Coated Catheters Admixed/Impregnated Catheters Impregnated Catheters Silver: Processed Catheters Clinical Studies on Antimicrobial Shunt and EVD catheters Hydrogel: Coated Catheters Admixed/Impregnated Catheters Impregnated Catheters Silver: Processed Catheters Conclusions References science_30 Biomaterials for Spinal Cord Repair Abbreviations An Introduction to Spinal Cord Injury Anatomy of the Spinal Cord The Tissue Response to SCI Animal Models of SCI Small animal models Large animal models Current Treatment Strategies and Clinical Trials Biomaterials for Drug Delivery Hydrogels Control of drug release Polymeric Particles Biomaterials for Cell Delivery Nerve Guidance Channels Scaffolds Future Outlook References science_31 Keratoprostheses Abbreviations The Cornea and the Need for Corneal Replacement Keratoprosthesis Dohlman-Doane KPro Osteoodonto KPro Seoul-Type KPro AlphaCor KPro BIOKPro SupraDescemetic KPro Aachen KPro Other KPro Materials Developments Biological Enhancement of KPros Conclusion References science_32 Retina Reconstruction Abbreviations The Retina Basic Structure and Function of the Neurosensory Retina The RPE-BrM Complex Blood Supply of the Retina Ocular Diseases Associated with Retinal Degeneration Age-Related Macular Degeneration Retinal Degeneration Retinal Reconstruction Transplantation Success and Failure Retinal Transplantation Challenges in Retina Reconstruction Rationale Retinal Pigment Epithelium Bruch's Membrane Choriocapillaris Neuronal Regeneration of the Adult Nervous System: Regeneration in the Central Nervous System Versus Peripheral Ne Interdependence Scaffold Biocompatibility Material Physical Constraint of the Subretinal Space Mechanical Properties Scaffold Fabrication Micro- and Nanotopography Microfabricated Scaffolds 3D Scaffolds Surface Modification of Scaffolds Controlled Release The CNS Environment Conclusions References science_33 Development of Contact Lenses from a Biomaterial Point of View - Materials, Manufacture, and Clinical Application... Glossary Abbreviations Introduction General Properties of Hydrogel Materials of Relevance to Contact Lenses Optical Transparency Mechanical Properties Surface Properties Water Content Oxygen Permeability Fluid and Ion Permeability Refractive Index Swell Factor and Dimensional Stability Conventional Hydrogel Contact Lens Materials Historical Development Polymeric Formulations High Water Content Hydrogel Lenses Strategies for Enhancing Lens Comfort Silicone Hydrogel Contact Lens Materials The Drive for Increased Corneal Oxygenation The Challenge of Incorporating Silicone into Hydrogel Materials The Launch of Silicone Hydrogel Lenses Surface Treatments Material Modulus of Elasticity Lens Edge Design `Second Generation´ Silicone Hydrogel Lenses Optimizing Surface Characteristics Classification of Soft Contact Lens Materials Soft Contact Lens Manufacture Lathe Cutting Spin Casting Cast Molding Reproducibility and Quality of Mass-Produced Lenses Clinical Ramifications of Polymer and Manufacturing Developments Polymer Developments: Enhanced Corneal Oxygenation Manufacturing Developments: Planned Lens Replacement Conclusions Classification of Soft Lens Materials FDA Classification System ACLM Classification System BS EN ISO 18369-1: 2006 Example References science_34 Bioartificial Kidney Glossary Abbreviations Overview of Renal Replacement Ultrafiltration and Small-Solute Clearance Tubular Reabsorption and Secretion Metabolic and Endocrine Function Membranes for Small-Solute Clearance Dialysis Hemofiltration Advancements in Membrane Technology Renal Epithelial Cell Therapy Device Design and Fabrication Renal assist device Bioartificial renal epithelial cell system Metabolic Replacement In vitro evaluation of the RAD In vitro evaluation of the BRECS Immunomodulation Preclinical Evaluation of Bioartificial Kidney Acute Renal Failure End-Stage Renal Disease Clinical Evaluation of Bioartificial Kidney Acute Renal Failure Phase I clinical studies of the RAD Phase II clinical studies of the RAD End-Stage Renal Disease Future Prospects Microelectromechanical System and Extracellular Fluid Volume Sensing Wearable Artificial Kidney Implantable Artificial Kidney References Relevant Websites science_35 Surgical Adhesion and Its Prevention Glossary Abbreviations Introduction Formation of Adhesions and Major Areas of Concern Pathophysiology of Adhesion Formation Peritoneum and Urinary and Reproductive Peritoneum Urinary and reproductive Tendon, Ligament, and Joint Pericardium Barriers to Adhesion: Current Clinical Practice Solid Barriers (Membranes/Mechanical Barriers) Resorbables Polysaccharide-based PEG-based (polyethylene glycol) Other polymers Other Nonresorbables Polytetrafluoroethylene Polypropylene Other Resorbable Spray-on, Gel, and Liquid Barriers Spray-on Gel Liquid Nonbarrier Methods Hybrid systems Transgene/drug/pharmacologic agent therapies Barriers to Adhesion: Current Research Uses for Adhesion Discussion Complications of Barrier Films Inflammation Nutrient deprivation Potential late adhesion development Design of New Barrier Films Drug-eluting barrier materials to reduce inflammation and increase fibrinolysis Allow penetration of nutrients and removal of waste (MW>1M) Bioresorbable, but does not form microscopic pieces on degradation (inflammatory) Technique and Assessment Summary References science_36 Suture Material: Conventional and Stimuli Responsive Abbreviations Introduction Properties of Suture Materials Tensile Strength Tissue Absorption Cross-Sectional Diameter Coefficient of Friction Knot Security and Strength Elasticity Plasticity Memory Handling Tissue Reactivity Origin and Physical Configuration Capillarity Fluid Absorption Ease of Removal and Color Sutures Absorbable Suture Materials (Table1) Surgical gut Polyglactin 910 (coated Vicryl, Vicryl Rapide, and coated Vicryl Plus) Polyglycolic acid (Dexon, Dexon II) Poliglecaprone (Monocryl) Polydioxanone Polyglycolide-trimethylene carbosnate (Maxon) Caprosyn Nonabsorbable Suture Materials (Table2) Silk (Mersilk, Perma-Hand) Polybutester (Novafil) Braided polyester (Mersilene, Ethibond, Surgidac) Nylon (Ethilon, Monosof, Nurolon, Surgilon, Supramid) Polypropylene (Prolene, Surgilene) ePFTE (Gore-Tex CV4) Stainless steel Other Sutures Barbed suture (Quill SRS, Monderm, Coveidin) Staples Skin Staples Nonabsorbable staples (Proximate, Royal Autosuture) Absorbable staples (Insorb) Ligatures Stapling Devices in Abdominal and Thoracic Surgery Surgical Needles Anatomy of a Needle Point Types Body Types Selection of Needles Conclusions References science_37 Staple Line Reinforcement Materials Glossary Abbreviations Introduction Staple Line Reinforcement Etiology of Anastomotic Complications Buttress Material Properties Reinforcement Materials Absorbable Material Fibrin glue Cellulose Polyglycolic acid/trimethylene carbonate Polysaccharidic polyglycuronates biopolymers Semiabsorbable Material Nonabsorbable Material Discussion References science_38 Biomaterials for Hernia Repair Glossary Introduction Why Are Biomaterials Essential in Hernia Surgery? Limitations of Biomaterials in the Field of Hernia Surgery History of Biomaterials in Hernia Surgery Initially Used Materials Averseness to Biomaterials Acceptance of Biomaterials Materials Used in Hernia Surgery Synthetic Fiber Polymers Polypropylene (e.g., Marlex, Prolene) Polyester Polytetrafluorethylene Polyvinylidene fluoride Composite meshes Biological Materials Hernia Surgery with Prostheses Inguinal Herniae Open techniques with mesh Lichtenstein Plug and patch repair Laparoscopic techniques (TAPP and TEP) Ventral Hernia Repair Open mesh techniques Onlay technique Sublay technique Laparoscopic technique (IPOM) Hiatus Hernia Repair with Mesh Forces Acting on Hernia Meshes Biomaterial Reinforces a Closed Defect Biomaterial Covers Defect Requirements for Hernia Meshes Physical Stability to Tissue Secretions Biocompatibility No Carcinogenicity Tensile Strength Elasticity Thickness and Bending Properties Mesh Weight Surface Properties Mesh coating Microhooks Antiadhesive coat Mesh to Hernia Size Relation Surgical techniques with closure of the hernia The mesh overlaps the defect Costs of Meshes Mesh Fixations Nonabsorbable Devices Suture Hernia stapler Spiral tacker Absorbable Fixation Systems Absorba tack Microhooks Fibrin glue Suture Potential Complications of Hernia Meshes Perioperative Complications Rejection Infection Chronic Complications Hernia recurrence Chronic pain Stiffening of the abdominal wall Conclusion and Future Perspectives Further Developments Conclusion References