Materials for Biomedical Engineering

Preface PART I: INTRODUCTION Chapter 1 Biomaterials - An Introductory Overview 1.1 Introduction 1.2 Definition and meaning of common terms 1.2.1 Biomaterial 1.2.2 Biocompatibility 1.2.3 Host Response 1.2.4 Categories of biomaterials 1.2.5 Bioactivity 1.2.6 Tissue engineering and regenerative medicine 1.2.7 In vivo, ex vivo and in vitro 1.3 Biomaterials design and selection 1.3.1 Evolving trend in biomaterials design 1.3.2 Factors in biomaterials design and selection 1.4 Properties of materials 1.4.1 Intrinsic properties of metals 1.4.2 Intrinsic properties of ceramics 1.4.3 Intrinsic properties of polymers 1.4.4 Properties of composites 1.4.5 Representation of properties 1.5 Case study in biomaterials design and selection: the hip implant 1.5.1 Femoral stem 1.5.2 Femoral head 1.5.3 Acetabular cup 1.5.4 Modern hip implants 1.6 Brief history of the evolution of biomaterials 1.6.1 Prior to World War II 1.6.2 A few decades after World War II 1.6.3 Contemporary period 1.7 Biomaterials an interdisciplinary field 1.8 Concluding remark Problems References and further reading PART II MATERIALS SCIENCE OF BIOMATERIALS Chapter 2 Atomic Structure and Bonding 2.1 Introduction 2.2 Atomic structure and bonding 2.3 Interatomic forces and bonding energies 2.4 Types of bonds between atoms and molecules 2.5 Primary bonds 2.5.1 The octet rule 2.5.2 Electronegativity of atoms 2.5.3 Polarity of covalent bonds 2.6 Ionic bonding 2.7 Covalent bonding 2.7.1 Hybrid orbitals 2.7.2 Covalent bonding in ceramics 2.7.3 Covalent bonding in polymers 2.8 Metallic bonding 2.9 Secondary bonds 2.9.1 Van der Waals bonding 2.9.2 Hydrogen bonding 2.10 Atomic bonding and structure in proteins 2.10.1 Primary structure 2.10.2 Secondary structure 2.10.3 Tertiary structure 2.10.4 Quaternary structure 2.11 Concluding remarks Problems References and further reading Chapter 3 Structure of Solids 3.1 Introduction 3.2 Packing of atoms in crystals 3.2.1 Unit cells and crystal systems 3.3 Structure of solids used as biomaterials 3.3.1 Crystal structure of metals 3.3.2 Crystal structure of ceramics 3.3.3 Structure of inorganic glasses 3.3.4 Structure of carbon materials 3.3.5 Structure of polymers 3.4 Defects in crystalline solids 3.4.1 Point defects 3.4.2 Line defects: dislocations 3.4.3 Planar defects: surfaces and grain boundaries 3.5 Microstructure of biomaterials 3.5.1 Microstructure of dense biomaterials 3.5.2 Microstructure of porous biomaterials 3.6 Special topic: Lattice planes and lattice directions 3.6.1 Unit cell geometry 3.6.2 Lattice positions 3.6.3 Lattice planes 3.6.4 Lattice directions 3.7 Concluding remarks Problems References Chapter 4 Bulk Properties of Materials 4.1 Introduction 4.2 Mechanical properties of materials 4.2.1 Mechanical stress and strain 4.2.2 Elastic modulus 4.2.3 Mechanical response of materials 4.2.4 Stress strain behavior of metals, ceramics and polymers 4.2.5 Fracture of materials 4.2.6 Toughness and fracture toughness 4.2.7 Fatigue 4.2.8 Hardness 4.3 Effect of microstructure on mechanical properties 4.3.1 Effect of porosity 4.3.2 Effect if grain size 4.4 Designing with ductile and brittle materials 4.4.1 Designing with metals 4.4.2 Designing with ceramics 4.4.3 Designing with polymers 4.5 Electrical properties 4.5.1 Electrical conductivity of materials 4.5.2 Electrical conductivity of conducting polymers 4.6 Magnetic properties 4.6.1 Origins of magnetic response in materials 4.6.2 Meaning and definition of relevant magnetic properties 4.6.3 Diamagnetic and paramagnetic materials 4.6.4 Ferromagnetic materials 4.6.5 Ferrimagnetic materials 4.6.6 Magnetization curves and hysteresis 4.6.7 Hyperthermia treatment of tumors using magnetic nanoparticle 4.7 Thermal properties 4.7.1 Thermal conductivity 4.7.2 Thermal expansion coefficient 4.8 Optical properties 4.9 Concluding remarks Problems References and further reading Chapter 5 Surface Properties of Materials 5.1 Introduction 5.2 Surface energy 5.2.1 Determination of surface energy of materials 5.2.2 Measurement of contact angle 5.2.3 Effects of surface energy 5.3 Surface chemistry 5.3.1 Characterization of surface chemistry 5.4 Surface charge 5.4.1 Surface charging mechanisms 5.4.2 Measurement of surface charge and potential 5.4.3 Effect of surface charge 5.5 Surface topography 5.5.1 Surface roughness parameters 5.5.2 Characterization of surface topography 5.5.3 Effect of surface topography on cell and tissue response 5.6 Concluding remarks Problems References and further reading PART III CLASSES OF MATERIALS USED IN BIOMEDICAL APPLICATIONS Chapter 6 Metals used as Biomaterials 6.1 Introduction 6.2 Crystal structure of metals 6.3 Polymorphic transformation 6.3.1 Formation of nuclei of critical size 6.3.2 Rate of phase transformation 6.3.3 Diffusive transformations 6.3.4 Displacive transformations 6.3.5 Time temperature transformation (TTT) diagrams 6.4 Alloys 6.5 Shape (morphology) of phases 6.5.1 Phase diagram principles: The Fe C phase diagram 6.5.2 Composition structure property relationships in carbon steels 6.6 Production methods 6.6.1 Wrought metal products 6.6.2 Cast metal products 6.6.3 Alternative production methods 6.7 Strengthening metals 6.7.1 Solid solution hardening 6.7.2 Precipitation and dispersion hardening 6.7.3 Work hardening 6.7.4 Grain size refinement 6.8 Classes of metals used as biomaterials 6.8.1 Stainless steels 6.8.2 Titanium and titanium alloys 6.8.3 Cobalt chromium alloys 6.8.4 Nickel titanium alloys 6.8.5 Tantalum 6.8.6 Zirconium alloys 6.8.7 Noble metals 6.9 Degradable metals 6.9.1 Designing degradable metals 6.9.2 Degradable magnesium alloys 6.10 Concluding remarks Problems References and further reading Chapter 7 Ceramic Biomaterials 7.1 Introduction 7.2 Design and processing of ceramics 7.2.1 Design principles for creating mechanically reliable ceramics 7.2.2 Principles of processing ceramics 7.3 Ceramics used as biomaterials 7.3.1 Chemically unreactive ceramics 7.3.2 Calcium phosphate compounds 7.3.3 Calcium phosphate cements 7.3.4 Calcium sulfate 7.4 Glasses 7.4.1 Glass transition temperature 7.4.2 Glass viscosity 7.4.3 Production of glasses 7.4.4 Chemically unreactive glasses 7.4.5 Bioactive glasses 7.5 Glass ceramics 7.5.1 Production of glass ceramics 7.5.2 Bioactive glass ceramics 7.5.3 Chemically unreactive glass ceramics 7.6 Concluding remarks Problems References and further reading Chapter 8 Synthetic Polymers I: Nondegradable Polymers 8.1 Introduction 8.2 Polymer science fundamentals 8.2.1 Copolymers 8.2.2 Linear and crosslinked molecules 8.2.3 Molecular symmetry and stereo-regularity 8.2.4 Molecular weight 8.2.5 Molecular conformation 8.2.6 Molecular conformation in amorphous polymers 8.2.7 Glass transition temperature 8.2.8 Semicrystalline polymers 8.2.9 Molecular orientation in amorphous and semicrystalline polymers 8.3 Production of polymers 8.3.1 Polymer synthesis 8.3.2 Production methods 8.4 Mechanical properties of polymers 8.4.1 Effect of temperature 8.4.2 Effect of crystallinity 8.4.3 Effect of molecular weight 8.4.4 Effect of molecular orientation 8.5 Thermoplastic polymers 8.5.1 Polyolefins 8.5.2 Fluorinated hydrocarbon polymers 8.5.3 Vinyl polymers 8.5.4 Acrylic polymers 8.5.5 Polyaryletherketones 8.5.6 Polysulfone, polyethersulfone and polycarbonate 8.5.7 Polyesters 8.5.8 Polyamides 8.6 Elastomeric polymers 8.6.1 Polydimethylsiloxane 8.7 Special topic: Polyurethanes 8.7.1 Production of polyurethanes 8.7.2 Structure property relations in polyurethanes 8.7.3 Chemical stability of polyurethanes in vivo 8.7.4 Biomedical applications of polyurethanes 8.8 Water-soluble polymers 8.9 Concluding remarks Problems References and further reading Chapter 8 Synthetic Polymers II: Degradable Polymers 9.1 Introduction 9.2 Degradation of polymers 9.3 Erosion of polymers 9.4 Characterization of degradation and erosion 9.5 Factors controlling polymer degradation 9.5.1 Chemical structure 9.5.2 pH 9.5.3 Copolymerization 9.5.4 Crystallinity 9.5.5 Molecular weight 9.5.6 Water uptake 9.6 Factors controlling polymer erosion 9.6.1 Bulk erosion 9.6.2 Surface erosion 9.7 Design criteria for degradable polymers 9.8 Types of degradable polymers relevant to biomaterials 9.8.1 Poly(alpha-hydroxy esters) 9.8.2 Polycaprolactone 9.8.3 Polyanhydrides 9.8.4 Poly(ortho esters) 9.8.5 Polydioxanone 9.8.6 Polyhydroxyalkanoates 9.8.7 Poly(propylene fumarate) 9.8.8 Polyacetals and polyketals 9.8.9 Poly(polyol sebacate) 9.8.10 Polycarbonates 9.9 Concluding remarks Problems References and further reading Chapter 10 Natural Polymers 10.1 Introduction 10.2 General properties and characteristics of natural polymers 10.3 Protein-based natural polymers 10.3.1 Collagen 10.3.2 Gelatin 10.3.3 Silk 10.3.4 Elastin 10.3.5 Fibrin 10.3.6 Laminin 10.4 Polysaccharide-based natural polymers 10.4.1 Hyaluronic acid 10.4.2 Sulfated glycosaminoglycans 10.4.3 Alginate 10.4.4 Chitosan 10.4.5 Agarose 10.4.6 Cellulose 10.4.7 Bacterial (microbial) cellulose 10.5 Concluding remarks Problems References Chapter 11 Hydrogels 11.1 Introduction 11.2 Characteristics of hydrogels 11.3 Types of hydrogels 11.4 Creation of hydrogels 11.4.1 Chemical hydrogels 11.4.2 Physical hydrogels 11.5 Characterization of sol to gel transition 11.6 Swelling behavior of hydrogels 11.6.1 Theory of swelling 11.6.2 Determination of swelling parameters 11.7 Mechanical properties of hydrogels 11.8 Transport properties of hydrogels 11.9 Surface properties of hydrogels 11.10 Environmentally responsive hydrogels 11.10.1 pH responsive hydrogels 11.10.2 Temperature responsive hydrogels 11.11 Synthetic hydrogels 11.11.1 Polyethylene glycol and polyethylene oxide 11.11.2 Polyvinyl alcohol 11.11.3 Polyhydroxyethyl methacrylate 11.11.4 Polyacrylic acid and polymethacrylic acid 11.11.5 Poly(N-isopropyl acrylamide) 11.12 Natural hydrogels 11.13 Application of hydrogels 11.12.1 Drug delivery 11.12.2 Cell encapsulation and immunoisolation 11.12.3 Scaffolds for tissue engineering 11.14 Concluding remarks Problems References Chapter 12 Composite Biomaterials 12.1 Introduction 12.2 Types of composites 12.3 Mechanical properties of composites 12.3.1 Mechanical properties of fiber composites 12.3.2 Mechanical properties of particulate composites 12.4 Biomedical applications of composites 12.5 Concluding remarks Problems References Chapter 13 Surface Modification and Biological Functionalization of Biomaterial 13.1 Introduction 13.2 Surface modification 13.3 Surface modification methods 13.4 Plasma processes 13.4.1 Plasma treatment principles 13.4.2 Advantages and drawbacks of plasma treatment 13.4.3 Applications of plasma treatment 13.5 Chemical vapor deposition 13.5.1 Chemical vapor deposition of inorganic films 13.5.2 Chemical vapor deposition of polymer films 13.6 Physical methods of surface modification 13.7 Parylene coating 13.8 Radiation grafting 13.9 Chemical reactions 13.10 Solution processing of coatings 13.10.1 Silanization 13.10.2 Langmuir Blodgett films 13.10.3 Self-assembled monolayers 13.10.4 Layer-by-layer deposition 13.11 Biological functionalization of biomaterials 13.11.1 Immobilization of biomolecules on biomaterials 13.11.2 Physical immobilization 13.11.3 Chemical immobilization 13.11.4 Heparin modification of biomaterials 13.12 Concluding remarks Problems References PART IV DEGRADATION OF BIOMATERIALS IN THE PHYSIOLOGICAL ENVIRONMENT Chapter 14 Degradation of Metallic and Ceramic Biomaterials 14.1 Introduction 14.2 Corrosion of metals 14.2.1 Principles of corrosion 14.2.2 Rate of corrosion 14.2.3 Pourbaix diagrams 14.2.4 Types of corrosion 14.3 Corrosion of metals in the physiological environment 14.3.1 Minimizing metal implant corrosion in vivo 14.4 Degradation of ceramics in the physiological environment 14.4.1 Degradation by dissolution and disintegration 14.4.2 Cell-mediated degradation 14.5 Concluding remarks Problems References Chapter 15 Degradation of Polymeric Biomaterials 15.1 Introduction 15.2 Hydrolytic degradation 15.2.1 Hydrolytic degradation pathways 15.2.2 Role of the physiological environment 15.2.3 Effect of local pH changes 15.2.4 Effect of inorganic ions 15.2.5 Effect of bacteria 15.3 Enzyme-catalyzed hydrolysis 15.3.1 Principles of enzyme-catalyzed hydrolysis 15.3.2 Role of enzymes in hydrolytic degradation in vitro 15.3.3 Role of enzymes in hydrolytic degradation in vivo 15.4 Oxidative degradation 15.4.1 Principles of oxidative degradation 15.4.2 Production of radicals and reactive species in vivo 15.4.3 Role of radicals and reactive species in oxidative degradation 15.5 Other types of degradation 15.5.1 Stress cracking 15.5.2 Metal-ion induced oxidative degradation 15.5.3 Oxidative degradation induced by the external environment 15.6 Concluding remarks Problems References PART V BIOCOMPATIBILITY PHENOMENA Chapter 16 Biocompatibility Fundamentals 16.1 Introduction 16.2 Biocompatibility phenomena with implanted devices 16.2.1 Consequences of failed biocompatibility 16.2.2 Basic pattern of biocompatibility phenomena 16.3 Protein and cell interactions with biomaterial surfaces 16.3.1 Protein adsorption onto biomaterials 16.3.2 Cell biomaterial interactions 16.4 Cells and organelles 16.4.1 Plasma membrane 16.4.2 Cell nucleus 16.4.3 Ribosomes, endoplasmic reticulum, and the Golgi apparatus 16.4.4 Mitochondria 16.4.5 Cytoskeleton 16.5 Extracellular matrix and tissues 16.5.1 Components of extracellular matrix 16.5.2 Attachment factors 16.5.3 Adhesion factors 16.5.4 Molecular and physical factors in cell attachment 16.5.5 Tissue types and organs 16.6 Plasma and blood cells 16.6.1 Erythrocytes 16.6.2 Leukocytes 16.7 Platelet adhesion to biomaterial surface 16.8 Platelets and the coagulation process 16.9 Cell types and their roles in biocompatibility phenomena 16.10 Concluding remarks Problems References and further reading Chapter 17 Mechanical Factors in Biocompatibility Phenomena 17.1 Introduction 17.2 Stages and mechanisms of mechanotransduction 17.2.1 Force transduction pathways 17.2.2 Signal transduction pathways and other mechanisms 17.2.3 Mechanisms of cellular response 17.3 Mechanical stress-induced biocompatibility phenomena 17.3.1 Implantable devices in bone healing 17.3.2 Implantable devices in the cardiovascular system 17.3.3 Implants in soft tissue healing 17.3.4 Stem cells in tissue engineering 17.4 Outcomes of transduction of extracellular stresses and responses 17.5 Concluding remarks Problems References and Further Reading Chapter 18 Inflammatory Reactions to Biomaterials 18.1 Introduction 18.2 Implant interaction with plasma proteins 18.3 Formation of provisional matrix 18.4 Acute inflammation and neutrophils 18.4.1 Neutrophil activation and extravasation 18.4.2 Formation of oxygen radicals 18.4.3 Phagocytosis by neutrophils 18.4.4 Neutrophil extracellular traps 18.4.5 Neutrophil apoptosis 18.5 Chronic inflammation and macrophages 18.5.1 Macrophage differentiation and recruitment to implant surfaces 18.5.2 Phagocytosis by M1 macrophages 18.5.3 Generation of oxidative radicals by M1 macrophages 18.5.4 Anti-inflammatory activities of M2 macrophages 18.6 Granulation tissue 18.7 Foreign body response 18.8 Fibrosis and fibrous encapsulation 18.9 Resolution of inflammation 18.10 Inflammation and biocompatibility 18.11 Concluding remarks Problems References and further Reading Chapter 19 Immune Responses to Biomaterials 19.1. Introduction 19.2 Adaptive immune system 19.2.1 Lymphocyte origins of two types of immune defense 19.2.2 Antibody characteristics and classes 19.2.3 Major histocompatibility complex and self-tolerance 19.2.4 B cell activation and release of antibodies 19.2.5 T cell development and cell mediated immunity 19.3 The complement system 19.4 Adaptive immune responses to biomaterials 19.4.1 Hypersensitivity responses 19.4.2 Immune responses to protein biomaterials and complexes 19.5 Designing biomaterials to modulate immune responses 19.6 Concluding remarks Problems References Appendix Chapter 20 Implant-Associated Infections 20.1 Introduction 20.2 Bacteria associated with implant infections 20.3 Biofilms and their characteristics 20.4 Sequence of biofilm formation on implant surfaces 20.4.1 Passive reversible adhesion of bacteria to an implant surface 20.4.2 Specific irreversible attachment of bacterial cells to implant surface 20.4.3 Microcolony expansion and formation of biofilm matrix 20.4.4 Biofilm maturation and tower formation 20.4.5 Dispersal and return to planktonic state 20.5 Biomaterial characteristics that affect bacterial adhesion 20.6 Biofilm shielding of infection from host defenses and antibiotics 20.7 Biofilm effects on host tissues and biomaterial interactions 20.8 Strategies for controlling implant infections 20.8.1 Orthopedic implants designed for rapid tissue integration 20.8.2 Surface nanotopography 20.8.3 Silver nanoparticles 20.8.4 Anti-biofilm polysaccharides 20.8.5 Bacteriophage therapy 20.8.6 Mechanical disruption 20.9 Concluding remarks Problems References and further reading Chapter 21 Response to Surface Topography and Particulate Materials 21.1 Introduction 21.2 Effects of biomaterial surface topography on cell response 21.2.1 Microscale surface roughness in osseointegration 21.2.2 Micropatterned and nanopatterned surfaces in macrophage differentiation 21.2.3 Micropatterned surfaces in neural regeneration 21.3 Biomaterial surface topography for antimicrobial activity 21.3.1 Microscale topography with antimicrobial activity 21.3.2 Submicron scale topography for antimicrobial activity 21.3.3 Nanoscale topography with antimicrobial activity 21.4 Microparticle-induced host responses 21.4.1 Mechanisms of microparticle endocytosis 21.4.2 Response to microparticles 21.4.3 Microparticle distribution in the organs 21.4.4 The inflammasome and particle induced inflammation 21.4.5 Wear debris-induced osteolysis 21.5 Nanoparticle-induced host responses 21.5.1 Mechanisms of nanoparticle endocytosis 21.5.2 Response to nanoparticles 21.5.3 Cytotoxicity effects of nanoparticles 21.6 Concluding remarks Problems References Chapter 22 Tests of Biocompatibility of Prospective Implant Materials 22.1 Introduction 22.2 Biocompatibility standards and regulations 22.2.1 ISO 10993 22.2.2 FDA guidelines and requirements 22.3 In vitro biocompatibility test procedures 22.3.1 Cytotoxicity tests 22.3.2 Genotoxicity tests 22.3.3 Hemocompatibility test 22.4 In vivo biocompatibility test procedures 22.4.1 Implantation tests 22.4.2 Thrombogenicity tests 22.4.3 Irritation and sensitization tests 22.4.4 Systemic toxicity tests 22.5 Clinical trials of biomaterials 22.6 Regulatory review and approval 22.7 Case study: The Proplast temporomandibular joint 22.8 Concluding remarks Problems References and further reading PART VI APPLICATIONS OF BIOMATERIALS Chapter 23 Biomaterials for Hard Tissue Repair 23.1 Introduction 23.2 Healing of bone fracture 23.2.1 Mechanisms of fracture healing 23.2.2 Internal fracture fixation devices 23.3 Healing of bone defects 23.3.1 Bone defects 23.3.2 Bone grafts 23.3.3 Bone graft substitutes 23.3.4 Healing of non-structural bone defects 23.3.5 Healing of structural bone defects 23.4 Total joint replacement 23.4.1 Total hip arthroplasty 23.4.2 Total knee arthroplasty 23.5 Spinal fusion 23.5.1 Biomaterials for spinal fusion 23.6 Dental implants and restorations 23.6.1 Dental implants 23.6.2 Indirect dental restorations 23.6.3 Direct dental restorations 23.7 Concluding remarks Problems References and further reading Chapter 24 Biomaterials for Soft Tissue Repair 24.1 Introduction 24.2 Surgical sutures and adhesives 24.2.1 Sutures 24.2.2 Soft tissue adhesives 24.3 The cardiovascular system 24.3.1 Major anatomical features of the cardiovascular system 24.3.2 Vascular grafts 24.3.3 Balloon angioplasty 24.3.4 Intravascular stents 24.3.5 Prosthetic heart valves 24.4 Ophthalmologic applications 24.4.1 Contact lenses 24.4.2 Intraocular lenses 24.5 Skin wound healing 24.5.1 Fundamentals of skin wound healing 24.5.2 Complicating factors in skin wound healing 24.5.3 Biomaterials-based therapies for skin wound healing 24.5.4 Nanoparticle-based therapies for skin wound healing 24.6 Concluding remarks Problems References and further reading Chapter 25 Biomaterials for Tissue Engineering and Regenerative Medicine 25.1 Introduction 25.2 Principles of tissue engineering and regenerative medicine 25.2.1 Cells for tissue engineering 25.2.2 Biomolecules and nutrients for ex vivo tissue engineering 25.2.3 Growth factors for tissue engineering 25.2.4 Cell therapy 25.2.5 Gene therapy 25.3 Biomaterials and scaffolds for tissue engineering 25.3.1 Properties of scaffolds for tissue engineering 25.3.2 Biomaterials for tissue engineering scaffolds 25.3.3 Porous solids 25.3.4 Hydrogels 25.3.5 Extracellular matrix scaffolds 25.4 Techniques for creating tissue engineering scaffolds 25.4.1 Creation of scaffolds in the form of porous solids 25.4.2 Electrospinning 25.4.3 Additive manufacturing (3D printing) techniques 25.4.4 Formation of hydrogel scaffolds 25.4.5 Preparation of extracellular matrix scaffolds 25.5 Three-dimensional (3D) bioprinting 25.5.1 Inkjet-based bioprinting 25.5.2 Microextrusion-based bioprinting 25.6 Tissue engineering for the regeneration of functional tissues and organs 25.6.1 Bone tissue engineering 25.6.2 Articular cartilage tissue engineering 25.6.3 Articular joints 25.6.4 Tendons and ligaments 25.6.5 Skin tissue engineering 25.6.6 Bladder tissue engineering 25.7 Concluding remarks Problems References and further reading Chapter 26 Biomaterials for Drug Delivery 26.1 Introduction 26.2 Controlled drug delivery 26.2.1 Drug delivery systems 26.2.2 Mechanisms of drug release 26.3 Designing biomaterials for drug delivery systems 26.4 Microparticle-based drug delivery systems 26.4.1 Preparation of polymer-based microsphere delivery systems 26.4.2 Applications of microparticle-based delivery systems 26.5 Hydrogel-based drug delivery systems 26.5.1 Environmentally responsive drug delivery systems 26.5.2 Drug delivery systems responsive to external physical stimuli 26.6 Nanoparticle-based drug delivery systems 26.6.1 Fate of nanoparticles 26.6.2 Targeting of nanoparticles to cells 26.6.3 Polymer nanoparticle-based systems 26.6.4 Lipid-based nanoparticles 26.6.5 Polymer conjugates 26.6.6 Dendrimers 26.6.7 Inorganic nanoparticles 26.7 Delivery of ribonucleic acid (RNA) 26.7.1 Modification of siRNA 26.7.2 Biomaterials for siRNA delivery 26.8 Biological drug delivery systems 26.8.1 Exosomes for therapeutic biomolecule delivery 26.9 Concluding remarks Problems References and further reading