Materials for Biomedical Engineering

Mohamed N. Rahaman, Professor Emeritus of Materials Science and Engineering, Missouri University of Science and Technology, USA. Dr. Rahaman is a Fellow of the American Ceramic Society, the author of five textbooks, the author and co-author of over 280 reviewed journal articles and conference proceedings, and the co-inventor on three US patents in the area of medical devices.Roger F. Brown, Professor Emeritus of Biological Sciences, Missouri University of Science and Technology, USA. Dr Brown is the author and co-author of over 60 reviewed journal articles and conference proceedings, and is a co-inventor on one US patent pertaining to the use of bioactive borate glass microfibers for soft tissue repair.

• Preface xixAbout the Companion Website xxiPart I General Introduction 11 Biomaterials – An Introductory Overview 31.1 Introduction 31.2 Definition and Meaning of Common Terms 31.3 Biomaterials Design and Selection 81.3.1 Evolving Trend in Biomaterials Design 81.3.2 Factors in Biomaterials Design and Selection 91.4 Properties of Materials 111.4.1 Intrinsic Properties of Metals 111.4.2 Intrinsic Properties of Ceramics 111.4.3 Intrinsic Properties of Polymers 121.4.4 Properties of Composites 121.4.5 Representation of Properties 131.5 Case Study in Materials Design and Selection: The Hip Implant 131.6 Brief History of the Evolution of Biomaterials 171.7 Biomaterials – An Interdisciplinary Field 191.8 Concluding Remarks 19Part II Materials Science of Biomaterials 212 Atomic Structure and Bonding 232.1 Introduction 232.2 Interatomic Forces and Bonding Energies 232.3 Types of Bonds between Atoms and Molecules 262.4 Primary Bonds 272.4.1 Ionic Bonding 292.4.2 Covalent Bonding 302.4.3 Metallic Bonding 332.5 Secondary Bonds 342.5.1 Van der Waals Bonding 342.5.2 Hydrogen Bonding 352.6 Atomic Bonding and Structure in Proteins 362.6.1 Primary Structure 362.6.2 Secondary Structure 372.6.3 Tertiary Structure 382.6.4 Quaternary Structure 432.7 Concluding Remarks 443 Structure of Solids 473.1 Introduction 473.2 Packing of Atoms in Crystals 473.2.1 Unit Cells and Crystal Systems 493.3 Structure of Solids Used as Biomaterials 513.3.1 Crystal Structure of Metals 513.3.2 Crystal Structure of Ceramics 523.3.3 Structure of Inorganic Glasses 543.3.4 Structure of Carbon Materials 553.3.5 Structure of Polymers 573.4 Defects in Crystalline Solids 583.4.1 Point Defects 593.4.2 Line Defects: Dislocations 593.4.3 Planar Defects: Surfaces and Grain Boundaries 623.5 Microstructure of Biomaterials 623.5.1 Microstructure of Dense Biomaterials 633.5.2 Microstructure of Porous Biomaterials 643.6 Special Topic: Lattice Planes and Directions 653.7 Concluding Remarks 674 Bulk Properties of Materials 694.1 Introduction 694.2 Mechanical Properties of Materials 694.2.1 Mechanical Stress and Strain 704.2.2 Elastic Modulus 724.2.3 Mechanical Response of Materials 744.2.4 Stress–Strain Behavior of Metals, Ceramics, and Polymers 784.2.5 Fracture of Materials 794.2.6 Toughness and Fracture Toughness 824.2.7 Fatigue 824.2.8 Hardness 834.3 Effect of Microstructure on Mechanical Properties 844.3.1 Effect of Porosity 844.3.2 Effect of Grain Size 854.4 Designing with Ductile and Brittle Materials 854.4.1 Designing with Metals 854.4.2 Designing with Ceramics 854.4.3 Designing with Polymers 874.5 Electrical Properties 874.5.1 Electrical Conductivity of Materials 874.5.2 Electrical Conductivity of Conducting Polymers 884.6 Magnetic Properties 884.6.1 Origins of Magnetic Response in Materials 884.6.2 Meaning and Definition of Relevant Magnetic Properties 894.6.3 Diamagnetic and Paramagnetic Materials 894.6.4 Ferromagnetic Materials 904.6.5 Ferrimagnetic Materials 914.6.6 Magnetization Curves and Hysteresis 914.6.7 Hyperthermia Treatment of Tumors using Magnetic Nanoparticles 914.7 Thermal Properties 924.7.1 Thermal Conductivity 924.7.2 Thermal Expansion Coefficient 934.8 Optical Properties 944.9 Concluding Remarks 955 Surface Properties of Materials 995.1 Introduction 995.2 Surface Energy 1005.2.1 Determination of Surface Energy of Materials 1015.2.2 Measurement of Contact Angle 1025.2.3 Effect of Surface Energy 1045.3 Surface Chemistry 1045.3.1 Characterization of Surface Chemistry 1055.4 Surface Charge 1085.4.1 Surface Charging Mechanisms 1085.4.2 Measurement of Surface Charge and Potential 1095.4.3 Effect of Surface Charge 1105.5 Surface Topography 1105.5.1 Surface Roughness Parameters 1125.5.2 Characterization of Surface Topography 1125.5.3 Effect of Surface Topography on Cell and Tissue Response 1155.6 Concluding Remarks 116Part III Classes of Materials Used as Biomaterials 1196 Metallic Biomaterials 1216.1 Introduction 1216.2 Crystal Structure of Metals 1216.3 Polymorphic Transformation 1226.3.1 Formation of Nuclei of Critical Size 1236.3.2 Rate of Phase Transformation 1236.3.3 Diffusive Transformations 1246.3.4 Displacive Transformations 1256.3.5 Time-Temperature-Transformation (TTT) Diagrams 1256.4 Alloys 1266.5 Shape (Morphology) of Phases 1266.6 Phase Diagrams 1276.7 Production of Metals 1296.7.1 Wrought Metal Products 1296.7.2 Cast Metal Products 1306.7.3 Alternative Production Methods 1306.8 Mechanisms for Strengthening Metals 1316.8.1 Solid Solution Hardening 1316.8.2 Precipitation and Dispersion Hardening 1316.8.3 Work Hardening 1316.8.4 Grain Size Refinement 1326.9 Metals Used as Biomaterials 1336.9.1 Stainless Steels 1336.9.2 Titanium and Titanium Alloys 1346.9.3 Cobalt-Based Alloys 1376.9.4 Nickel-Titanium Metals and Alloys 1416.9.5 Tantalum 1436.9.6 Zirconium Alloys 1446.9.7 Noble Metals 1446.10 Degradable Metals 1456.10.1 Designing Degradable Metals 1456.10.2 Degradable Magnesium Alloys 1466.11 Concluding Remarks 1497 Ceramic Biomaterials 1537.1 Introduction 1537.2 Design and Processing of Ceramics 1547.2.1 Design Principles for Mechanically Reliable Ceramics 1547.2.2 Principles of Processing Ceramics 1557.3 Chemically Unreactive Ceramics 1577.3.1 Alumina (Al2O3) 1577.3.2 Zirconia (ZrO2) 1587.3.3 Alumina–Zirconia (Al2O3–ZrO2) Composites 1607.3.4 Silicon Nitride (Si3N4) 1617.4 Calcium Phosphates 1627.4.1 Solubility of Calcium Phosphates 1637.4.2 Degradation of Calcium Phosphates 1647.4.3 Hydroxyapatite 1647.4.4 Beta-Tricalcium Phosphate (β-TCP) 1657.4.5 Biphasic Calcium Phosphate (BCP) 1657.4.6 Other Calcium Phosphates 1667.4.7 Mechanical Properties of Calcium Phosphates 1677.5 Calcium Phosphate Cement (CPC) 1677.5.1 CPC Chemistry 1687.5.2 CPC Setting (Hardening) Mechanism 1687.5.3 Microstructure of CPCs 1687.5.4 Properties of CPCs 1697.6 Calcium Sulfate 1707.7 Glasses 1707.7.1 Glass Transition Temperature (Tg) 1717.7.2 Glass Viscosity 1717.7.3 Production of Glasses 1727.8 Chemically Unreactive Glasses 1727.9 Bioactive Glasses 1737.9.1 Bioactive Glass Composition 1737.9.2 Mechanism of Conversion to Hydroxyapatite 1747.9.3 Reactivity of Bioactive Glasses 1757.9.4 Mechanical Properties of Bioactive Glasses 1767.9.5 Release of Ions from Bioactive Glasses 1777.9.6 Applications of Bioactive Glasses 1787.10 Glass-Ceramics 1797.10.1 Production of Glass-Ceramics 1797.10.2 Bioactive Glass-Ceramics 1807.10.3 Chemically Unreactive Glass-Ceramics 1817.10.4 Lithium Disilicate Glass-Ceramics 1817.11 Concluding Remarks 1838 Synthetic Polymers I: Nondegradable Polymers 1878.1 Introduction 1878.2 Polymer Science Fundamentals 1888.2.1 Copolymers 1888.2.2 Linear and Crosslinked Molecules 1898.2.3 Molecular Symmetry and Stereoregularity 1898.2.4 Molecular Weight 1908.2.5 Molecular Conformation 1928.2.6 Glass Transition Temperature (Tg) 1938.2.7 Semicrystalline Polymers 1948.2.8 Molecular Orientation in Amorphous and Semicrystalline Polymers 1978.3 Production of Polymers 1988.3.1 Polymer Synthesis 1988.3.2 Production Methods 1998.4 Mechanical Properties of Polymers 1998.4.1 Effect of Temperature 1998.4.2 Effect of Crystallinity 2008.4.3 Effect of Molecular Weight 2008.4.4 Effect of Molecular Orientation 2008.5 Thermoplastic Polymers 2018.5.1 Polyolefins 2018.5.2 Fluorinated Hydrocarbon Polymers 2038.5.3 Vinyl Polymers 2048.5.4 Acrylic Polymers 2048.5.5 Polyaryletherketones 2058.5.6 Polycarbonate, Polyethersulfone, and Polysulfone 2068.5.7 Polyesters 2068.5.8 Polyamides 2068.6 Elastomeric Polymers 2078.6.1 Polydimethylsiloxane (PDMS) 2088.7 Special Topic: Polyurethanes 2098.7.1 Production of Polyurethanes 2098.7.2 Structure–Property Relations in Polyurethanes 2108.7.3 Chemical Stability of Polyurethanes in vivo 2118.7.4 Biomedical Applications of Polyurethanes 2128.8 Water-soluble Polymers 2128.9 Concluding Remarks 2139 Synthetic Polymers II: Degradable Polymers 2179.1 Introduction 2179.2 Degradation of Polymers 2179.3 Erosion of Degradable Polymers 2189.4 Characterization of Degradation and Erosion 2199.5 Factors Controlling Polymer Degradation 2199.5.1 Chemical Structure 2199.5.2 pH 2209.5.3 Copolymerization 2219.5.4 Crystallinity 2229.5.5 Molecular Weight 2229.5.6 Water Uptake 2239.6 Factors Controlling Polymer Erosion 2239.6.1 Bulk Erosion 2249.6.2 Surface Erosion 2249.7 Design Criteria for Degradable Polymers 2259.8 Types of Degradable Polymers Relevant to Biomaterials 2269.8.1 Poly(α-hydroxy Esters) 2269.8.2 Polycaprolactone 2309.8.3 Polyanhydrides 2319.8.4 Poly(Ortho Esters) 2339.8.5 Polydioxanone 2349.8.6 Polyhydroxyalkanoates 2359.8.7 Poly(Propylene Fumarate) 2369.8.8 Polyacetals and Polyketals 2379.8.9 Poly(polyol sebacate) 2389.8.10 Polycarbonates 2409.9 Concluding Remarks 24110 Natural Polymers 24510.1 Introduction 24510.2 General Properties and Characteristics of Natural Polymers 24610.3 Protein-Based Natural Polymers 24610.3.1 Collagen 24710.3.2 Gelatin 25510.3.3 Silk 25610.3.4 Elastin 25910.3.5 Fibrin 26010.3.6 Laminin 26110.4 Polysaccharide-Based Polymers 26210.4.1 Hyaluronic Acid 26310.4.2 Sulfated Polysaccharides 26510.4.3 Alginates 26710.4.4 Chitosan 26910.4.5 Agarose 27110.4.6 Cellulose 27210.4.7 Bacterial (Microbial) Cellulose 27410.5 Concluding Remarks 27511 Hydrogels 27911.1 Introduction 27911.2 Characteristics of Hydrogels 27911.3 Types of Hydrogels 28111.4 Creation of Hydrogels 28111.4.1 Chemical Hydrogels 28111.4.2 Physical Hydrogels 28211.5 Characterization of Sol to Gel Transition 28411.6 Swelling Behavior of Hydrogels 28511.6.1 Theory of Swelling 28511.6.2 Determination of Swelling Parameters 28811.7 Mechanical Properties of Hydrogels 28911.8 Transport Properties of Hydrogels 28911.9 Surface Properties of Hydrogels 29011.10 Environmentally Responsive Hydrogels 29111.10.1 pH Responsive Hydrogels 29111.10.2 Temperature Responsive Hydrogels 29311.11 Synthetic Hydrogels 29411.11.1 Polyethylene Glycol and Polyethylene Oxide 29411.11.2 Polyvinyl Alcohol 29711.11.3 Polyhydroxyethyl Methacrylate 29811.11.4 Polyacrylic Acid and Polymethacrylic Acid 29811.11.5 Poly(N-isopropyl acrylamide) 29811.12 Natural Hydrogels 29911.13 Applications of Hydrogels 30111.13.1 Drug Delivery 30111.13.2 Cell Encapsulation and Immunoisolation 30211.13.3 Scaffolds for Tissue Engineering 30211.14 Concluding Remarks 30312 Composite Biomaterials 30712.1 Introduction 30712.2 Types of Composites 30712.3 Mechanical Properties of Composites 30712.3.1 Mechanical Properties of Fiber Composites 30812.3.2 Mechanical Properties of Particulate Composites 30912.4 Biomedical Applications of Composites 31112.5 Concluding Remarks 31313 Surface Modification and Biological Functionalization of Biomaterials 31513.1 Introduction 31513.2 Surface Modification 31513.3 Surface Modification Methods 31613.4 Plasma Processes 31713.4.1 Plasma Treatment Principles 31713.4.2 Advantages and Drawbacks of Plasma Treatment 31813.4.3 Applications of Plasma Treatment 31813.5 Chemical Vapor Deposition 31913.5.1 Chemical Vapor Deposition of Inorganic Films 31913.5.2 Chemical Vapor Deposition of Polymer Films 31913.6 Physical Techniques for Surface Modification 32213.7 Parylene Coating 32213.8 Radiation Grafting 32313.9 Chemical Reactions 32313.10 Solution Processing of Coatings 32413.10.1 Silanization 32413.10.2 Langmuir–Blodgett Films 32513.10.3 Self-Assembled Monolayers 32813.10.4 Layer-by-Layer Deposition 32913.11 Biological Functionalization of Biomaterials 33013.11.1 Immobilization Methods 33113.11.2 Physical Immobilization 33113.11.3 Chemical Immobilization 33213.11.4 Heparin Modification of Biomaterials 33413.12 Concluding Remarks 337Part IV Degradation of Biomaterials in the Physiological Environment 33914 Degradation of Metallic and Ceramic Biomaterials 34114.1 Introduction 34114.2 Corrosion of Metals 34214.2.1 Principles of Metal Corrosion 34214.2.2 Rate of Corrosion 34514.2.3 Pourbaix Diagrams 34614.2.4 Types of Electrochemical Corrosion 34714.3 Corrosion of Metal Implants in the Physiological Environment 34914.3.1 Minimizing Metal Implant Corrosion in vivo 35114.4 Degradation of Ceramics 35114.4.1 Degradation by Dissolution and Disintegration 35114.4.2 Cell-Mediated Degradation 35214.5 Concluding Remarks 35315 Degradation of Polymeric Biomaterials 35515.1 Introduction 35515.2 Hydrolytic Degradation 35615.2.1 Hydrolytic Degradation Pathways 35615.2.2 Role of the Physiological Environment 35715.2.3 Effect of Local pH Changes 35715.2.4 Effect of Inorganic Ions 35815.2.5 Effect of Bacteria 35815.3 Enzyme-Catalyzed Hydrolysis 35815.3.1 Principles of Enzyme-Catalyzed Hydrolysis 35915.3.2 Role of Enzymes in Hydrolytic Degradation in vitro 36015.3.3 Role of Enzymes in Hydrolytic Degradation in vivo 36215.4 Oxidative Degradation 36215.4.1 Principles of Oxidative Degradation 36315.4.2 Production of Radicals and Reactive Species in vivo 36315.4.3 Role of Radicals and Reactive Species in Degradation 36615.4.4 Oxidative Degradation of Polymeric Biomaterials 36715.5 Other Types of Degradation 36915.5.1 Stress Cracking 36915.5.2 Metal Ion-Induced Oxidative Degradation 37015.5.3 Oxidative Degradation Induced by the External Environment 37015.6 Concluding Remarks 371Part V Biocompatibility Phenomena 37316 Biocompatibility Fundamentals 37516.1 Introduction 37516.2 Biocompatibility Phenomena with Implanted Devices 37516.2.1 Consequences of Failed Biocompatibility 37616.2.2 Basic Pattern of Biocompatibility Processes 37716.3 Protein and Cell Interactions with Biomaterial Surfaces 37816.3.1 Protein Adsorption onto Biomaterials 37816.3.2 Cell–Biomaterial Interactions 37816.4 Cells and Organelles 38016.4.1 Plasma Membrane 38016.4.2 Cell Nucleus 38216.4.3 Ribosomes, Endoplasmic Reticulum, and the Golgi Apparatus 38416.4.4 Mitochondria 38616.4.5 Cytoskeleton 38616.4.6 Cell Contacts and Membrane Receptors 38816.5 Extracellular Matrix and Tissues 38916.5.1 Components of the Extracellular Matrix 38916.5.2 Attachment Factors 38916.5.3 Cell Adhesion Molecules 39016.5.4 Molecular and Physical Factors in Cell Attachment 39116.5.5 Tissue Types and Origins 39116.6 Plasma and Blood Cells 39316.6.1 Erythrocytes 39316.6.2 Leukocytes 39516.7 Platelet Adhesion to Biomaterial Surfaces 39616.8 Platelets and the Coagulation Process 39616.9 Cell Types and Their Roles in Biocompatibility Phenomena 39816.10 Concluding Remarks 39917 Mechanical Factors in Biocompatibility Phenomena 40117.1 Introduction 40117.2 Stages and Mechanisms of Mechanotransduction 40117.2.1 Force Transduction Pathways 40117.2.2 Signal Transduction Pathways and Other Mechanisms 40317.2.3 Mechanisms of Cellular Response 40417.3 Mechanical Stress-Induced Biocompatibility Phenomena 40717.3.1 Implantable Devices in Bone Healing 40717.3.2 Implantable Devices in the Cardiovascular System 40817.3.3 Soft Tissue Healing 41017.3.4 Stem Cells in Tissue Engineering 41117.4 Outcomes of Transduction of Extracellular Stresses and Responses 41417.5 Concluding Remarks 41418 Inflammatory Reactions to Biomaterials 41718.1 Introduction 41718.2 Implant Interaction with Plasma Proteins 41818.3 Formation of Provisional Matrix 41818.4 Acute Inflammation and Neutrophils 41918.4.1 Neutrophil Activation and Extravasation 41918.4.2 Formation of Reactive Oxygen Species 42118.4.3 Phagocytosis by Neutrophils 42118.4.4 Neutrophil Extracellular Traps (NETs) 42118.4.5 Neutrophil Apoptosis 42318.5 Chronic Inflammation and Macrophages 42318.5.1 Macrophage Differentiation and Recruitment to Implant Surfaces 42318.5.2 Phagocytosis by M1 Macrophages 42418.5.3 Generation of Oxidative Radicals by M1 Macrophages 42518.5.4 Anti-inflammatory Activities of M2 Macrophages 42518.6 Granulation Tissue 42618.7 Foreign Body Response 42718.8 Fibrosis and Fibrous Encapsulation 42918.9 Resolution of Inflammation 43018.10 Inflammation and Biocompatibility 43118.11 Concluding Remarks 43319 Immune Responses to Biomaterials 43719.1 Introduction 43719.2 Adaptive Immune System 43719.2.1 Lymphocyte Origins of Two Types of Adaptive Immune Defense 43819.2.2 Antibody Characteristics and Classes 43819.2.3 Major Histocompatibility Complex and Self-Tolerance 43919.2.4 B Cell Activation and Release of Antibodies 44019.2.5 T Cell Development and Cell-Mediated Immunity 44019.3 The Complement System 44319.4 Adaptive Immune Responses to Biomaterials 44319.4.1 Hypersensitivity Responses 44419.4.2 Immune Responses to Protein-Based Biomaterials and Complexes 44519.5 Designing Biomaterials to Modulate Immune Responses 44619.6 Concluding Remarks 44720 Implant-Associated Infections 44920.1 Introduction 44920.2 Bacteria Associated with Implant Infections 45020.3 Biofilms and their Characteristics 45020.4 Sequence of Biofilm Formation on Implant Surfaces 45120.4.1 Passive Reversible Adhesion of Bacteria to Implant Surface 45220.4.2 Specific Irreversible Attachment of Bacteria to Implant Surface 45220.4.3 Microcolony Expansion and Formation of Biofilm Matrix 45220.4.4 Biofilm Maturation and Tower Formation 45320.4.5 Dispersal and Return to Planktonic State 45320.5 Effect of Biomaterial Characteristics on Bacterial Adhesion 45320.6 Biofilm Shielding of Infection from Host Defenses and Antibiotics 45420.7 Effects of Biofilm on Host Tissues and Biomaterial Interactions 45420.8 Strategies for Controlling Implant Infections 45620.8.1 Orthopedic Implants Designed for Rapid Tissue Integration 45620.8.2 Surface Nanotopography 45720.8.3 Silver Nanoparticles 45820.8.4 Anti-biofilm Polysaccharides 45820.8.5 Bacteriophage Therapy 45820.8.6 Mechanical Disruption 45920.9 Concluding Remarks 46021 Response to Surface Topography and Particulate Materials 46321.1 Introduction 46321.2 Effect of Biomaterial Surface Topography on Cell Response 46421.2.1 Microscale Surface Topography in Osseointegration 46621.2.2 Microscale and Nanoscale Patterned Surfaces in Macrophage Differentiation 46921.2.3 Microscale Patterned Surfaces in Neural Regeneration 47021.3 Biomaterial Surface Topography for Antimicrobial Activity 47121.3.1 Microscale Topography with Antimicrobial Activity 47121.3.2 Nanoscale Topography with Antimicrobial Activity 47721.4 Microparticle-Induced Host Responses 48221.4.1 Mechanisms of Microparticle Endocytosis 48221.4.2 Response to Microparticles 48321.4.3 Microparticle Distribution in the Organs 48721.4.4 The Inflammasome and Microparticle-Induced Inflammation 48821.4.5 Wear Debris-Induced Osteolysis 48821.5 Nanoparticle-Induced Host Responses 48921.5.1 Mechanisms of Nanoparticle Endocytosis 48921.5.2 Response to Nanoparticles 48921.5.3 Cytotoxicity Effects of Nanoparticles 49221.6 Concluding Remarks 49622 Tests of Biocompatibility of Prospective Implant Materials 49922.1 Introduction 49922.2 Biocompatibility Standards and Regulations 49922.2.1 ISO 10993 49922.2.2 FDA Guidelines and Requirements 50022.3 In vitro Biocompatibility Test Procedures 50022.3.1 Cytotoxicity Tests 50022.3.2 Genotoxicity Tests 50222.3.3 Hemocompatibility Tests 50422.4 In vivo Biocompatibility Test Procedures 50722.4.1 Implantation Tests 50722.4.2 Thrombogenicity Tests 50922.4.3 Irritation and Sensitization Tests 51022.4.4 Systemic Toxicity Tests 51122.5 Clinical Trials of Biomaterials 51122.6 FDA Review and Approval 51222.7 Case Study: The Proplast Temporomandibular Joint 51222.8 Concluding Remarks 513Part VI Applications of Biomaterials 51523 Biomaterials for Hard Tissue Repair 51723.1 Introduction 51723.2 Healing of Bone Fracture 51823.2.1 Mechanism of Fracture Healing 51823.2.2 Internal Fracture Fixation Devices 52023.3 Healing of Bone Defects 52123.3.1 Bone Defects 52123.3.2 Bone Grafts 52123.3.3 Bone Graft Substitutes 52323.3.4 Healing of Nonstructural Bone Defects 52723.3.5 Healing of Structural Bone Defects 53223.4 Total Joint Replacement 53523.4.1 Total Hip Arthroplasty 53523.4.2 Total Knee Arthroplasty 53623.5 Spinal Fusion 53623.5.1 Biomaterials for Spinal Fusion 53823.6 Dental Implants and Restorations 53923.6.1 Dental Implants 53923.6.2 Direct Dental Restorations 53923.6.3 Indirect Dental Restorations 54023.7 Concluding Remarks 54324 Biomaterials for Soft Tissue Repair 54724.1 Introduction 54724.2 Surgical Sutures and Adhesives 54824.2.1 Sutures 54824.2.2 Soft Tissue Adhesives 54924.3 The Cardiovascular System 55024.3.1 The Heart 55024.3.2 The Circulatory System 55124.4 Vascular Grafts 55124.4.1 Desirable Properties and Characteristics of Synthetic Vascular Grafts 55224.4.2 Synthetic Vascular Graft Materials 55224.4.3 Patency of Vascular Grafts 55224.5 Balloon Angioplasty 55524.6 Intravascular Stents 55624.6.1 Bare-Metal Stents 55624.6.2 Drug-Eluting Stents 55724.6.3 Degradable Stents 55724.7 Prosthetic Heart Valves 55824.7.1 Mechanical Valves 55824.7.2 Bioprosthetic Valves 55924.8 Ophthalmologic Applications 56024.8.1 Contact Lenses 56124.8.2 Intraocular Lenses 56324.9 Skin Wound Healing 56624.9.1 Skin Wound Healing Fundamentals 56724.9.2 Complicating Factors in Skin Wound Healing 56924.9.3 Biomaterials-Based Therapies 56924.9.4 Nanoparticle-Based Therapies 57424.10 Concluding Remarks 57625 Biomaterials for Tissue Engineering and Regenerative Medicine 58125.1 Introduction 58125.2 Principles of Tissue Engineering and Regenerative Medicine 58225.2.1 Cells for Tissue Engineering 58425.2.2 Biomolecules and Nutrients for in vitro Cell Culture 58725.2.3 Growth Factors for Tissue Engineering 58725.2.4 Cell Therapy 58825.2.5 Gene Therapy 58925.3 Biomaterials and Scaffolds for Tissue Engineering 58925.3.1 Properties of Scaffolds for Tissue Engineering 58925.3.2 Biomaterials for Tissue Engineering Scaffolds 59125.3.3 Porous Solids 59125.3.4 Hydrogels 59425.3.5 Extracellular Matrix (ECM) Scaffolds 59425.4 Creation of Scaffolds for Tissue Engineering 59525.4.1 Creation of Scaffolds in the Form of Porous Solids 59625.4.2 Electrospinning 60125.4.3 Additive Manufacturing (3D Printing) Techniques 60325.4.4 Formation of Hydrogel Scaffolds 60825.4.5 Preparation of Extracellular Matrix (ECM) Scaffolds 60825.5 Three-dimensional Bioprinting 60925.5.1 Inkjet-Based Bioprinting 60925.5.2 Microextrusion-Based Bioprinting 61125.6 Tissue Engineering Techniques for the Regeneration of Functional Tissues and Organs 61425.6.1 Bone Tissue Engineering 61425.6.2 Articular Cartilage Tissue Engineering 61525.6.3 Tissue Engineering of Articular Joints 61825.6.4 Tissue Engineering of Tendons and Ligaments 62125.6.5 Skin Tissue Engineering 62425.6.6 Bladder Tissue Engineering 62625.7 Concluding Remarks 62926 Biomaterials for Drug Delivery 63326.1 Introduction 63326.2 Controlled Drug Release 63426.2.1 Drug Delivery Systems 63626.2.2 Mechanisms of Drug Release 63626.3 Designing Biomaterials for Drug Delivery Systems 63826.4 Microparticle-based Delivery Systems 63826.4.1 Preparation of Polymer Microsphere Delivery Systems 63926.4.2 Applications of Microparticle Delivery Systems 64026.5 Hydrogel-based Delivery Systems 64026.5.1 Environmentally Responsive Drug Delivery Systems 64126.5.2 Drug Delivery Systems Responsive to External Physical Stimuli 64426.6 Nanoparticle-based Delivery Systems 64826.6.1 Distribution and Fate of Nanoparticle-based Drug Delivery Systems 64926.6.2 Targeting of Nanoparticles to Cells 65026.6.3 Polymer-based Nanoparticle Systems 65326.6.4 Lipid-based Nanoparticle Systems 65526.6.5 Polymer Conjugates 66326.6.6 Dendrimers 66626.6.7 Inorganic Nanoparticles 66726.7 Delivery of Ribonucleic Acid (RNA) 66826.7.1 Chemical Modification of siRNA 67026.7.2 Biomaterials for siRNA Delivery 67126.8 Biological Drug Delivery Systems 67526.8.1 Exosomes for Therapeutic Biomolecule Delivery 67526.9 Concluding Remarks 676Index 681