Nanomedicine, Volume IIA: Biocompatibility
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Robert A. Freitas Jr.
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About this bookNanomedicine, Volume IIA: BiocompatibilityThe safety, effectiveness, and utility of medical nanorobotic devices will critically depend upon their biocompatibility with human organs, tissues, cells, and biochemical systems. In this Volume, we broaden the definition of nanomedical biocompatibility to include all of the mechanical, physiological, immunological, cytological, and biochemical responses of the human body to the introduction of artificial medical nanodevices, whether “particulate” (large doses of independent micron-sized individual nanorobots) or “bulk” (nanorobotic organs assembled either as solid objects or built up from trillions of smaller artificial cells or docked nanorobots inside the body) in form. |
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Table of contentsChapter 15.1 Are Diamondoid Nanorobots Hazardous?...14 15.1.1 Mechanical Damage from Ingested Diamond...14 15.1.2 Mechanical Damage from Inhaled Diamond...18 Chapter 15.2 Classical Biocompatibility...25 15.2.1 Biocompatibility of Traditional Medical Implants...26 15.2.1.1 Orthopedic Biomaterials...26 15.2.1.2 Heart Valve Biomaterials...27 15.2.1.3 Bioactive Materials...28 15.2.1.4 Implant Infection and Biofilms...30 15.2.2 Adhesive Interactions with Implant Surfaces...33 15.2.2.1 Nonadhesive Nanorobot Surfaces...35 15.2.2.2 Adhesive Nanorobot Surfaces...39 15.2.2.3 Cell Response to Patterned Surfaces...42 15.2.2.4 Sorboregulatory and Adhesioregulatory Surfaces...44 15.2.3 Nanorobot Immunoreactivity...46 15.2.3.1 Overview of the Human Immune System...46 15.2.3.1.1 Nonspecific (Innate) Immune Response...46 15.2.3.1.2 Specific (Acquired) Immune Response...47 15.2.3.2 Complement Activation...50 15.2.3.3 Immunoglobulins (Antibodies)...56 15.2.3.4 Immunosuppression, Tolerization, and Camouflage...62 15.2.3.5 Immune Privilege...66 15.2.3.6 Immune Evasion...68 15.2.4 General Inflammation...71 15.2.5 Coagulation and Thrombogenicity...74 15.2.6 Allergic and Other Sensitivity Reactions...78 15.2.6.1 Allergic Reactions (Hypersensitivity)...79 15.2.6.2 Sternutogenesis...82 15.2.6.3 Nauseogenesis and Emetogenesis...83 15.2.6.4 Nanoid Shock...84 15.2.7 Nanopyrexia...86 15.2.8 Nanorobot Mutagenicity and Carcinogenicity...89 Chapter 15.3 Biocompatibility of Nanomedical Materials...94 15.3.1 Biocompatibility of Diamond...94 15.3.1.1 Protein Adsorption on Diamond Surfaces...94 15.3.1.2 Cell Response to Diamond Surfaces...97 15.3.1.3 Biocompatibility of Diamond-Coated Prostheses...99 15.3.1.4 Biocompatibility of Diamond Particles...100 15.3.1.5 Chemical Inertness of Diamond...103 15.3.2 Biocompatibility of Carbon Fullerenes...103 15.3.2.1 Pure Carbon Fullerenes...104 15.3.2.2 Derivatized Carbon Fullerenes...108 15.3.2.3 Fullerene-Based Pharmaceuticals...111 15.3.3 Biocompatibility of Nondiamondoid Carbon...113 15.3.3.1 Vitreous or Glassy Carbon...113 15.3.3.2 Pyrolytic or Low Temperature Isotropic Carbon...115 15.3.3.3 Graphite...117 15.3.3.4 Carbon Fiber Composites...118 15.3.3.5 Amorphous Carbon Particles...121 15.3.3.6 Corrosion Degradation Effects...126 15.3.4 Biocompatibility of Teflon...126 15.3.4.1 Protein Adsorption on Teflon Surfaces...127 15.3.4.2 Cell and Tissue Response to Bulk Teflon...129 15.3.4.3 Biocompatibility of Teflon-Coated Prostheses...132 15.3.4.4 Biocompatibility of Teflon Particles...134 15.3.4.5 Chemical Inertness of Teflon...138 15.3.5 Biocompatibility of Sapphire, Ruby, and Alumina...138 15.3.5.1 Protein Adsorption on Alumina and Sapphire...139 15.3.5.2 Sapphire Dental Implants...140 15.3.5.3 Tissue Response to Bulk Alumina and Sapphire...142 15.3.5.4 Cell Response to Bulk Alumina and Sapphire...144 15.3.5.5 Alumina and Sapphire Particles...146 15.3.5.6 Chemical Stability of Alumina and Sapphire...149 15.3.6 Biocompatibility of Other Nanomedical Materials...150 15.3.6.1 Biocompatibility of DNA...151 15.3.6.2 Biocompatibility of Nitinol...152 15.3.6.3 Biocompatibility of Metals, Semiconductors, and Quantum Dots...153 15.3.6.4 Biocompatibility of Dendrimers...154 15.3.6.5 Biocompatibility with Neural Cells...155 15.3.6.6 Biofouling of Medical Nanorobots...157 15.3.7 Biocompatibility of Nanorobot Effluents...158 15.3.8 Nanorobotic Thermocompatibility...159 Chapter 15.4 Systemic Nanorobot Distribution and Phagocytosis...164 15.4.1 Large Particle Movement...164 15.4.2 Geometrical Trapping of Bloodborne Medical Nanorobots...165 15.4.2.1 Geometrical Trapping in Lung Vasculature...166 15.4.2.2 Geometrical Trapping in Liver Vasculature...166 15.4.2.3 Geometrical Trapping in Spleen Vasculature...168 15.4.2.4 Geometrical Trapping in Kidney Vasculature...171 15.4.2.5 Geometrical Trapping Elsewhere in the Circulation...172 15.4.3 Phagocytosis of Medical Nanorobots...173 15.4.3.1 Phagocytes, Phagocytosis, and the RES...173 15.4.3.2 Phagocytosis of Bloodborne Microparticles...178 15.4.3.2.1 Phagocytosis and Opsonization in Blood...178 15.4.3.2.2 Phagocytosis in Lung Vasculature...179 15.4.3.2.3 Phagocytosis in Liver Vasculature...180 15.4.3.2.4 Phagocytosis in Spleen Vasculature...182 15.4.3.2.5 Phagocytosis in Kidney Vasculature...183 15.4.3.3 Particle Clearance from Nonsanguinous Spaces...184 15.4.3.3.1 Clearance of Particles from Tissues...184 15.4.3.3.2 Clearance of Ingested Particles...187 15.4.3.3.3 Clearance of Inhaled Particles...189 15.4.3.4 Particle Clearance from the Lymphatics...191 15.4.3.5 Foreign Body Granulomatous Reaction...195 15.4.3.6 Phagocyte Avoidance and Escape...199 15.4.3.6.1 Avoid Phagocytic Contact...200 15.4.3.6.2 Avoid Phagocytic Recognition...203 15.4.3.6.3 Avoid Phagocytic Binding and Activation...205 15.4.3.6.4 Inhibit Phagocytic Engulfment...207 15.4.3.6.5 Inhibit Enclosure and Scission...210 15.4.3.6.6 Induce Exocytosis of Phagosomal Vacuole...211 15.4.3.6.7 Inhibit Phagolysosomal Fusion...213 15.4.3.6.8 Inhibit Phagocyte Metabolism...214 15.4.3.6.9 Phagocytocide...215 15.4.3.6.10 Systemic Phagocytic Blockade...216 15.4.3.6.11 Artificial Biological Phagocytes...218 15.4.4 Biocompatibility of Nanorobot Fragments in vivo...218 Chapter 15.5 Nanorobot Mechanocompatibility...222 15.5.1 Mechanical Interaction with Human Integument...222 15.5.1.1 Pruritus...223 15.5.1.2 Epidermalgia and Allodynia...223 15.5.1.3 Epithelial Pressure Ulcers...224 15.5.1.4 Mechanical Peristaltogenesis and Mucosacompatibility...225 15.5.2 Histopenetration and Perforation...226 15.5.2.1 Transepithelial Penetration...226 15.5.2.2 Transendothelial Penetration, Bruising and Edema...227 15.5.2.3 Nanorobot Convoy Formation...229 15.5.3 Vascular Mechanocompatibility...229 15.5.3.1 Modulation of Endothelial Phenotype and Function...230 15.5.3.1.1 Fluid Shear Stress...230 15.5.3.1.2 Stretch Forces...232 15.5.3.2 Vascular Response to Stenting...234 15.5.3.3 Nanorobotic Obstructive Mechanical Vasculopathy...235 15.5.3.4 Nanorobotic Destructive Mechanical Vasculopathies...236 15.5.3.4.1 Nanorobotic Ulcerative Vasculopathy...236 15.5.3.4.2 Nanorobotic Lacerative Vasculopathy...237 15.5.3.4.3 Nanorobotic Concussive Vasculopathy...238 15.5.3.5 Reduction of Vascular Permeability by Nanoaggregates...240 15.5.3.6 Non-Occluding Indwelling Vascular Obstructions...240 15.5.4 Mechanocompatibility with Extracellular Matrix and Tissue Cells...241 15.5.4.1 Force Threshold for Biological Response...241 15.5.4.2 Mechanical Damage to Extracellular Matrix Proteins...244 15.5.4.3 Size and Force Threshold for Perceptible Histonatation...244 15.5.5 Mechanocompatibility with Nontissue Cells...245 15.5.5.1 Mechanical Interactions with Erythrocytes...245 15.5.5.1.1 Nanorobotic Hemolysis...245 15.5.5.1.2 Erythrocyte Surface Fluctuations and Elasticity...247 15.5.5.1.3 Disruption of Erythrocyte Aggregation...248 15.5.5.2 Mechanical Interactions with Platelets...249 15.5.5.2.1 Nanorobotic Thrombocytolysis...249 15.5.5.2.2 Disruption of Platelet Aggregation...249 15.5.5.3 Mechanical Interactions with Leukocytes...250 15.5.5.3.1 Nanorobotic Leukocytolysis...250 15.5.5.3.2 Leukocyte Surface Fluctuations and Elasticity...252 15.5.5.3.3 Leukocyte Margination and Migration...252 15.5.5.3.4 Disruption of Leukocyte Aggregation...254 15.5.5.4 Viability of Confined, Pressurized, or Desiccated Cells...254 15.5.6 Electrocompatibility...256 15.5.6.1 Electrical Interactions with Cells...257 15.5.6.2 Surface Electrical Thrombogenicity...259 15.5.7 Cytomembrane and Intracellular Mechanocompatibility...260 15.5.7.1 Mechanical Interactions with Glycocalyx...260 15.5.7.2 Mechanical Cell Membrane Disruptions...262 15.5.7.2.1 Natural Cell Membrane Wounding...262 15.5.7.2.2 Cytopuncture and Membrane Resealing...263 15.5.7.2.3 Resident Transmembrane Penetrators...264 15.5.7.2.4 Organelle Membrane Breach...265 15.5.7.3 Mechanical Interactions with Cytoskeleton...267 15.5.7.3.1 Mechanical Cytoskeleton Disorganization...268 15.5.7.3.2 Disruption of Molecular Motors and Vesicular Transport...270 15.5.7.4 Intracellular Cavitation, Shock Waves, Decompression Nucleation, and Ballooning...272 15.5.7.5 Mechanical Disruption of Intracellular Microzones...273 15.5.7.6 Mechanically-Induced Proteolysis, Apoptosis, or Prionosis...274 15.5.7.7 Macromolecular Cross-Interface Adhesion...275 15.5.8 Nanorobot-Nanorobot Mechanocompatibility...275 Chapter 15.6 Nanorobot Volumetric Intrusiveness...278 15.6.1 Somatic Intrusiveness...278 15.6.2 Bloodstream Intrusiveness...282 15.6.3 Cellular Intrusiveness...285 15.6.3.1 Membrane Elasticity and Cellular Expansion...285 15.6.3.2 Intracellular Lipofuscin and Storage Diseases...286 15.6.3.3 Intracellular Microspheres and Crystals...286 15.6.3.4 Phagocyte Ingesta...287 15.6.3.5 Intracellular Microbiota...287 15.6.3.6 Intracellular Nanorobot Intrusiveness...289 Afterword by ???...291 Glossary...293 References...295 Index...499 |
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