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Preface xi Contributors xiii 1 HISTORY OF BIOMIMETIC, BIOACTIVE, AND BIORESPONSIVE BIOMATERIALS 1 Matteo Santin and Gary Phillips 1.1 The First Generation of Biomaterials: The Search for ???The Bioinert??? 1 1.1.1 Bioinert: Myth, Reality, or Utopia? 4 1.2 The Second Generation of Biomaterials: Biomimetic, Bioresponsive, Bioactive 5 1.2.1 Hydroxyapatite (HA) and Bioglass®: Cell Adhesion and Stimulation 6 1.2.2 Collagen, Fibrin Glue, and Hyaluronic Acid Hydrogels: Presenting the ECM 6 1.2.3 Chitosan and Alginate: Replacing the ECM 9 1.2.4 Poly(Lactic/Glycolic) Acid Copolymers: Encouraging Tissue Remodeling by Safe Biodegradation 10 1.2.5 Porous Metals: Favoring Mechanical Integration 11 1.3 The Third–Generation Biomaterials: Biomimicking Natural Bioactive and Bioresponsive Processes 13 1.3.1 Principal Phases of Tissue Regeneration 14 1.3.1.1 Cell Adhesion: The Cornerstone of Tissue Regeneration 16 1.3.1.2 Mechanisms of Tissue Mineralization 19 1.4 Principles of Biomimesis and Bioactivity 21 1.4.1 Biomimicking of the ECM 22 1.4.2 Biomimicking of Cell Membrane Components 24 1.4.3 Biomimicking Cell Signaling Pathways 24 1.4.3.1 Modulation of the Growth Factor Signaling by Gene Expression: Bioactive Gene Delivery Systems 25 1.5 Bioactive Biomaterials from Different Natural Sources 26 1.5.1 Silk Fibroin 26 1.5.2 Soybean–Based Biomaterials 27 1.6 Scope of This Book 29 References 30 2 SOFT TISSUE STRUCTURE AND FUNCTIONALITY 35 Gabriela Voskerician 2.1 Overview 35 2.2 Epithelial Tissue 36 2.2.1 Background 36 2.3 The Skin 37 2.3.1 Structure and Functionality 37 2.3.2 Repair, Healing, and Renewal 42 2.4 Muscle Tissue 46 2.4.1 Background 46 2.4.2 Skeletal Muscle 48 2.4.2.1 Structure and Functionality 48 2.4.2.2 Repair, Healing, and Renewal 50 2.4.3 Smooth Muscle 51 2.4.3.1 Structure and Functionality 51 2.4.3.2 Repair, Healing, and Renewal 52 2.4.4 Cardiac Muscle 54 2.4.4.1 Structure and Functionality 54 2.4.4.2 Repair, Healing, and Renewal 55 2.5 Connective Tissue 56 2.5.1 Background 56 2.5.2 Embryonic Connective Tissue 57 2.5.3 Connective Tissue Proper 58 2.5.3.1 Cells of the Connective Tissue Proper 59 2.5.3.2 Connective Tissue Proper Fibers 60 2.5.3.3 Ground Substance 63 2.5.4 Specialized Connective Tissues 64 2.5.4.1 Structure and Function 64 2.5.4.2 Repair, Healing, and Renewal of Hyaline Cartilage 66 2.6 The Foreign Body Response 68 Exercises/Questions for Chapter 2 76 References 76 3 HARD TISSUE STRUCTURE AND FUNCTIONALITY 81 Antonio Merolli and Paolo Tranquilli Leali 3.1 Definition of Hard Tissues 81 3.2 Articular Cartilage 81 3.2.1 Structure of the Articular Cartilage 82 3.2.2 Specifi c Mechanism Repair of the Articular Cartilage 83 3.3 Bone Tissue 84 3.3.1 The Structure of the Bony Tissues 85 3.3.2 The Functions of Bone Tissue 86 3.3.3 Cell Types Involved in Bone Homeostasis: The Osteoblasts and the Osteoclasts 88 3.3.4 Ossifi cation, Turnover, and Remodeling 89 3.3.5 Bone Composite Structure and Its Effect on Mechanical Performance 91 3.4 Concluding Remarks 92 Exercises/Questions for Chapter 3 92 References 93 4 BIOMEDICAL APPLICATIONS OF BIOMIMETIC POLYMERS: THE PHOSPHORYLCHOLINE–CONTAINING POLYMERS 95 Andrew L. Lewis and Andrew W. Lloyd 4.1 Historical Perspective 95 4.2 Synthesis of PC–Containing Polymers 97 4.3 Physicochemical Properties of PC–Containing Polymers 98 4.3.1 Antifouling Mechanisms of Action 98 4.3.2 Swelling Phenomena and Structural Aspects of PC Coatings 100 4.4 Stability and Mechanical Property Considerations 102 4.4.1 PC Coatings and Surface Treatments 102 4.4.2 Bulk Hydrogels and Blends 104 4.5 Biological Compatibility 105 4.5.1 Interactions with Proteins, Eukaryotic Cells, and Bacteria 105 4.5.2 Interaction with Other Tissues 107 4.6. Applications of PC Polymers 107 4.6.1 Cardiovascular Applications 107 4.6.1.1 PC–Coated Coronary Stents 108 4.6.1.2 Vascular Grafts 108 4.6.1.3 Extracorporeal Circuits 109 4.6.2 Ophthalmic Applications 110 4.6.2.1 Intraocular Lenses 110 4.6.2.2 Contact Lenses 111 4.6.2.3 Other Ocular Devices 112 4.6.3 Anti–Infective Applications 112 4.6.3.1 Urological Devices 112 4.6.3.2 Tympanostomy Tubes 112 4.6.4 Orthopedic Applications 113 4.6.5 Biosensors and Diagnostics 113 4.6.6 Separation Systems 115 4.6.7 PC Polymers for Drug Delivery 116 4.6.7.1 Drug Delivery Coatings 116 4.6.7.2 Gel–Based Drug Delivery Systems 119 4.6.7.3 Nano/Micro Particulate Drug and Gene Delivery 119 4.6.7.4 Drug Conjugates 122 4.6.8 Emerging Applications 122 4.7 Summary 123 Exercises/Questions for Chapter 4 124 References 125 5 BIOMIMETIC, BIORESPONSIVE, AND BIOACTIVE MATERIALS: INTEGRATING MATERIALS WITH TISSUE 141 Roberto Chiesa and Alberto Cigada 5.1 Introduction 141 5.2 Mandatory Requirements for Metals as Implantable Materials 142 5.2.1 Stiffness 142 5.2.2 Strength 143 5.2.3 Corrosion Resistance 144 5.2.3.1 General Corrosion 144 5.2.3.2 Crevice Corrosion 145 5.2.3.3 Fretting Corrosion 145 5.2.3.4 Galvanic Corrosion 145 5.3 Biocompatibility of Metals 145 5.3.1 ISO Standardized Metal Family 146 5.3.1.1 Stainless Steels 146 5.3.1.2 Cobalt Alloys 148 5.3.1.3 Titanium and Titanium Alloys 149 5.4 Surface Treatments of Metals for Biomedical Applications 150 5.4.1 Cathodic Deposition Treatments 152 5.4.2 Anodic Oxidation 152 Exercises/Questions for Chapter 5 157 References 157 6 CERAMICS 161 Montserrat Espanol, Román A. Pérez, Edgar B. Montufar, and Maria–Pau Ginebra 6.1 Historical Perspective 161 6.2 Biostable Ceramics 162 6.2.1 Alumina 163 6.2.2 Zirconia 164 6.3 Bioactive and Resorbable Ceramics 165 6.3.1 Basic Concepts 165 6.3.2 Glasses and Glass???Ceramics 166 6.3.2.1 Physicochemical Properties of Bioactive Glasses 167 6.3.2.2 Silicate–Based Glasses 168 6.3.2.3 Phosphate–Based Glasses 170 6.3.2.4 Processing of Glass and Glass???Ceramics 170 6.3.3 Calcium Phosphates 172 6.3.3.1 Physicochemistry of Calcium Phosphates 172 6.3.3.2 Processing of Calcium Orthophosphates 175 6.3.4 New Trends in Bioactive and Resorbable Materials Integration 178 Exercises/Questions for Chapter 6 183 References 184 7 BIOFUNCTIONAL BIOMATERIALS OF THE FUTURE 191 Mário Barbosa, Gary Phillips, and Matteo Santin 7.1 Clinically Led Next Generation Biomaterials 191 7.1.1 Wound Dressings and Dermal Substitutes 192 7.1.2 Vascular Grafts and Cardiovascular Stents 193 7.1.3 Joint Implants and Cartilage Tissue Engineering 194 7.1.4 Bone Fillers 195 7.1.5 Nerve Guides 195 7.1.6 Ophthalmologic Devices 195 7.2 Biomacromolecule–Inspired Biomaterials 196 7.2.1 Artificial Laminin 196 7.2.2 Artificial Elastin 197 7.2.3 Artificial Collagen 197 7.2.4 GAG– and PGN–Mimicking Biomaterials 197 7.3 Nanostructured Biomimetic, Bioresponsive, and Bioactive Biomaterials 198 7.3.1 Nanofabrication of Biomaterials 198 7.3.1.1 2D Techniques 199 7.3.1.2 3D Techniques 199 7.3.1.3 Polymeric Dendrimers 200 7.3.1.4 Self–Assembling Peptides 201 7.4 Conclusions 202 Exercises/Questions for Chapter 7 203 References 203 Index 207