Оглавление
Mohamed N. Rahaman. Materials for Biomedical Engineering
Table of Contents
List of Tables
List of Illustrations
Guide
Pages
Materials for Biomedical Engineering. Fundamentals and Applications
Preface
About the Companion Website
1 Biomaterials – An Introductory Overview. 1.1 Introduction
1.2 Definition and Meaning of Common Terms
Biomaterial
Biocompatibility
Host Response
Categories of Biomaterials
Natural and Synthetic Biomaterials
Degradable, Nondegradable and Resorbable Biomaterials
Bioactivity
Tissue Engineering and Regenerative Medicine
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 Materials Design and Selection: The Hip Implant
Femoral Stem
Femoral Head
Acetabular Cup
Modern Hip Implants
1.6 Brief History of the Evolution of Biomaterials
Prior to World War II
A Few Decades After World War II
Contemporary Period
1.7 Biomaterials – An Interdisciplinary Field
1.8 Concluding Remarks
Problems
References
2 Atomic Structure and Bonding. 2.1 Introduction
2.2 Interatomic Forces and Bonding Energies
Relationship of Interatomic Force and Bonding Energy to Properties of Materials
2.3 Types of Bonds between Atoms and Molecules
2.4 Primary Bonds
The Octet Rule
NaCl Molecule
CH4 Molecule
Electronegativity of Atoms
Polarity of Covalent Bond
2.4.1 Ionic Bonding
Example 2.1
Solution:
2.4.2 Covalent Bonding
Hybrid Orbitals
Covalent Bonding in Ceramics
Covalent Bonding in Polymers
2.4.3 Metallic Bonding
2.5 Secondary Bonds
2.5.1 Van der Waals Bonding
2.5.2 Hydrogen Bonding
2.6 Atomic Bonding and Structure in Proteins
2.6.1 Primary Structure
2.6.2 Secondary Structure
Stereochemistry of the Amide Bond
Hydrogen Bonding
2.6.3 Tertiary Structure
Globular Proteins
Fibrous Proteins
2.6.4 Quaternary Structure
2.7 Concluding Remarks
Problems
Reference
Further Reading
3 Structure of Solids. 3.1 Introduction
3.2 Packing of Atoms in Crystals
3.2.1 Unit Cells and Crystal Systems
Unit Cell Parameters
Crystal Systems and Bravais Lattices
3.3 Structure of Solids Used as Biomaterials
3.3.1 Crystal Structure of Metals
Example 3.1
3.3.2 Crystal Structure of Ceramics
Crystal Structure of Hydroxyapatite
3.3.3 Structure of Inorganic Glasses
3.3.4 Structure of Carbon Materials
Fullerenes, Graphenes, and Carbon Nanotubes
3.3.5 Structure of Polymers
3.4 Defects in Crystalline Solids
3.4.1 Point Defects
3.4.2 Line Defects: Dislocations
Types of Dislocations
Slip or Plastic Deformation Resulting from Dislocation Motion
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 Directions
Unit Cell Geometry
Lattice Positions
Lattice Planes
Lattice Directions
3.7 Concluding Remarks
Problems
References
Further Reading
4 Bulk Properties of Materials. 4.1 Introduction
4.2 Mechanical Properties of Materials
4.2.1 Mechanical Stress and Strain
Uniaxial Tension and Compression
Shear Deformation
Torsional Deformation
Flexural Deformation (Bending)
4.2.2 Elastic Modulus
4.2.3 Mechanical Response of Materials
Elastic and Plastic Deformation
Elastic Limit and Yield Point
Definition and Determination of Strength
True Stress and Strain Versus Engineering (Nominal) Stress and Strain
Example 4.1
Solution:
Viscoelasticity
4.2.4 Stress–Strain Behavior of Metals, Ceramics, and Polymers
4.2.5 Fracture of Materials
Crack Formation
Crack Propagation
Theoretical Analysis of Brittle Fracture
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 of 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 Nanoparticles
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
Further Reading
5 Surface Properties of Materials. 5.1 Introduction
5.2 Surface Energy
5.2.1 Determination of Surface Energy of Materials
Example 5.1
Solution:
5.2.2 Measurement of Contact Angle
5.2.3 Effect of Surface Energy
5.3 Surface Chemistry
5.3.1 Characterization of Surface Chemistry
Auger Electron Spectroscopy (AES)
X‐ray Photoelectron Spectroscopy (XPS)
Secondary Ion Mass Spectroscopy (SIMS)
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
Scanning Electron Microscopy (SEM)
Atomic Force Microscopy (AFM)
Profilometry
5.5.3 Effect of Surface Topography on Cell and Tissue Response
5.6 Concluding Remarks
Problems
References
Further Readings
6 Metallic 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
6.6 Phase Diagrams
Phase Diagram Principles: The Fe‐C Phase Diagram
Example 6.1
Solution:
Composition–Structure–Property Relationships in Carbon Steels
6.7 Production of Metals
6.7.1 Wrought Metal Products
6.7.2 Cast Metal Products
6.7.3 Alternative Production Methods
6.8 Mechanisms for Strengthening Metals
6.8.1 Solid Solution Hardening
6.8.2 Precipitation and Dispersion Hardening
6.8.3 Work Hardening
6.8.4 Grain Size Refinement
6.9 Metals Used as Biomaterials
6.9.1 Stainless Steels
Martensitic Stainless Steels
Ferritic Stainless Steels
Austenitic Stainless Steels
6.9.2 Titanium and Titanium Alloys
Phase Diagrams for Titanium Alloys
Microstructure and Properties of Titanium Alloys
6.9.3 Cobalt‐Based Alloys
Cobalt–Chromium Phase Diagrams
Cobalt–Chromium–Molybdenum (Co–Cr–Mo) Phase Diagram
Microstructure and Mechanical Properties of Co–Cr–Mo Alloys
Microstructure and Mechanical Properties of Co–Cr–W–Ni
Co–Ni–Cr–Mo Alloys
6.9.4 Nickel‐Titanium Metals and Alloys
Shape Memory and Superelasticity of Nitinol
Phase Transformation in Nitinol
Use of Nitinol as a Biomaterial
6.9.5 Tantalum
6.9.6 Zirconium Alloys
6.9.7 Noble Metals
6.10 Degradable Metals
6.10.1 Designing Degradable Metals
6.10.2 Degradable Magnesium Alloys
Degradation of Magnesium Alloys
Example 6.2
Solution:
Alloying Elements
Mechanical Properties
Use of Degradable Magnesium Alloys as Biomaterials
6.11 Concluding Remarks
Problems
References
Further Reading
7 Ceramic Biomaterials. 7.1 Introduction
7.2 Design and Processing of Ceramics
7.2.1 Design Principles for Mechanically Reliable Ceramics
7.2.2 Principles of Processing Ceramics
The Sintering Process
Principles Underlying Sintering
Sintering Process Optimization
7.3 Chemically Unreactive Ceramics
7.3.1 Alumina (Al2O3)
7.3.2 Zirconia (ZrO2)
Crystallographic Transformation in ZrO2
Zirconia Phase Diagrams
Production of Stabilized ZrO2
Transformation Toughening Mechanism in Stabilized ZrO2
Orthopedic Applications of Stabilized ZrO2
7.3.3 Alumina–Zirconia (Al2O3–ZrO2) Composites
Zirconia Toughened Alumina (ZTA)
Alumina Matrix Composite (AMC)
7.3.4 Silicon Nitride (Si3N4)
Structure and Chemical Stability of Si3N4
Microstructure and Properties of Si3N4
Production of Si3N4
Orthopedic Applications of Si3N4
7.4 Calcium Phosphates
7.4.1 Solubility of Calcium Phosphates
Calcium Phosphate Solubility Phase Diagrams
7.4.2 Degradation of Calcium Phosphates
7.4.3 Hydroxyapatite
Structure and Composition of Hydroxyapatite
Production and Properties of Hydroxyapatite
7.4.4 Beta‐Tricalcium Phosphate (β‐TCP)
7.4.5 Biphasic Calcium Phosphate (BCP)
7.4.6 Other Calcium Phosphates. Tetracalcium Phosphate (TTCP)
Dicalcium Phosphate Dihydrate (DCPD)
Octacalcium Phosphate (OCP)
Calcium Deficient Hydroxyapatite (CDHA)
Amorphous Calcium Phosphate (ACP)
7.4.7 Mechanical Properties of Calcium Phosphates
7.5 Calcium Phosphate Cement (CPC)
7.5.1 CPC Chemistry
7.5.2 CPC Setting (Hardening) Mechanism
7.5.3 Microstructure of CPCs
7.5.4 Properties of CPCs
7.6 Calcium Sulfate
7.7 Glasses
7.7.1 Glass Transition Temperature (Tg)
7.7.2 Glass Viscosity
7.7.3 Production of Glasses
Example 7.1
Solution:
7.8 Chemically Unreactive Glasses
7.9 Bioactive Glasses
7.9.1 Bioactive Glass Composition
7.9.2 Mechanism of Conversion to Hydroxyapatite
7.9.3 Reactivity of Bioactive Glasses
Example 7.1
Solution
7.9.4 Mechanical Properties of Bioactive Glasses
7.9.5 Release of Ions from Bioactive Glasses
7.9.6 Applications of Bioactive Glasses
7.10 Glass‐Ceramics
7.10.1 Production of Glass‐Ceramics
7.10.2 Bioactive Glass‐Ceramics
7.10.3 Chemically Unreactive Glass‐Ceramics
7.10.4 Lithium Disilicate Glass‐Ceramics
Properties of Lithium Disilicate Glass‐Ceramics
7.11 Concluding Remarks
Problems
References
Further Reading
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 Stereoregularity
8.2.4 Molecular Weight
Example 8.1
Solution:
8.2.5 Molecular Conformation
Molecular Conformation in Amorphous Polymers
8.2.6 Glass Transition Temperature (Tg)
8.2.7 Semicrystalline Polymers
Crystallization of Polymers
Nucleation
Crystal Growth
8.2.8 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
Polyethylene (PE)
Ultrahigh Molecular Weight Polyethylene (UHMWPE)
Crosslinked UHMWPE
Example 8.2
Solution:
Polypropylene (PP)
8.5.2 Fluorinated Hydrocarbon Polymers
Polytetrafluoroethylene (PTFE)
8.5.3 Vinyl Polymers
8.5.4 Acrylic Polymers
PMMA Bone Cement
8.5.5 Polyaryletherketones
Polyether Ether Ketone (PEEK)
8.5.6 Polycarbonate, Polyethersulfone, and Polysulfone
8.5.7 Polyesters
Polyethylene Terephthalate (PET)
8.5.8 Polyamides
8.6 Elastomeric Polymers
8.6.1 Polydimethylsiloxane (PDMS)
Production of PDMS Elastomers
Physicochemical Properties of PDMS Elastomers
Applications of PDMS
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
Further Reading
9 Synthetic Polymers II : Degradable Polymers. 9.1 Introduction
9.2 Degradation of Polymers
9.3 Erosion of Degradable 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(α‐hydroxy Esters)
Polyglycolic Acid (PGA)
Polylactic Acid (PLA)
Poly(Lactic‐co‐Glycolic Acid) (PLGA)
Physicochemical Properties of PLGA
9.8.2 Polycaprolactone
9.8.3 Polyanhydrides
Compositional Effects on Degradation and Erosion
Biocompatibility of Polyanhydrides
Structure of Polyanhydrides
Physicochemical Properties of Polyanhydrides
9.8.4 Poly(Ortho Esters)
9.8.5 Polydioxanone
9.8.6 Polyhydroxyalkanoates
Structure and Properties of PHAs
Biocompatibility of PHAs
9.8.7 Poly(Propylene Fumarate)
9.8.8 Polyacetals and Polyketals
9.8.9 Poly(polyol sebacate)
Design and Synthesis of Poly(Glycerol Sebacate) (PGS)
Properties and Applications of PGS
9.8.10 Polycarbonates
Poly(Trimethylene Carbonate) (PTMC) and Its Copolymers
Tyrosine‐Derived Polycarbonates
9.9 Concluding Remarks
Problems
References
Further Readings
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
Structure of Fibrous Collagen (Type I)
Preparation of Collagen for Use as Biomaterials
Production of Collagen Biomaterials
Crosslinking of Collagen Biomaterials
Chemical Crosslinking
Physical Crosslinking
Effectiveness of Crosslinking Techniques
Properties of Collagen Biomaterials
Biocompatibility of Collagen Biomaterials
Degradation of Collagen Biomaterials
Thermal Stability of Collagen
Mechanical Properties of Collagen
Applications of Collagen Biomaterials
10.3.2 Gelatin
10.3.3 Silk
Composition and Structure of Silkworm Silk
Production of Silk Biomaterials
Properties and Applications of Silk Biomaterials
10.3.4 Elastin
10.3.5 Fibrin
10.3.6 Laminin
10.4 Polysaccharide‐Based Polymers
10.4.1 Hyaluronic Acid
Chemical Modification of Hyaluronic Acid
Properties and Applications of Hyaluronic Acid Biomaterials
10.4.2 Sulfated Polysaccharides
10.4.3 Alginates
Alginate Hydrogels
Chemical Modification of Alginates
Properties and Applications of Alginate Biomaterials
10.4.4 Chitosan
Chemical Modification of Chitosan
Properties and Applications of Chitosan
10.4.5 Agarose
10.4.6 Cellulose
10.4.7 Bacterial (Microbial) Cellulose
10.5 Concluding Remarks
Problems
References
Further Reading
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
Crosslinking by Free Radical Mechanism
Crosslinking by Chemical Reactions Between Functional Groups
11.4.2 Physical Hydrogels
Crosslinking by Ionic Bonds
Crosslinking by Secondary Bonds
Crosslinking by Physical Mechanisms
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
Chemical Modification of PEG Hydrogel
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 Applications of Hydrogels
11.13.1 Drug Delivery
11.13.2 Cell Encapsulation and Immunoisolation
11.13.3 Scaffolds for Tissue Engineering
11.14 Concluding Remarks
Problems
References
Further Readings
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
Example 12.1
Solution:
12.4 Biomedical Applications of Composites
12.5 Concluding Remarks
Problems
References
Further Readings
13 Surface Modification and Biological Functionalization of Biomaterials. 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
Principles and Mechanisms of CVD Polymerization
Advantages and Drawbacks of CVD Polymerization
13.6 Physical Techniques for 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
Principles of Langmuir–Blodgett Film Formation
Film Deposition Techniques
Properties and Applications of 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 Methods
13.11.2 Physical Immobilization
13.11.3 Chemical Immobilization
Immobilization Using Carbodiimide Chemistry
Immobilization Using Photochemical Methods
13.11.4 Heparin Modification of Biomaterials
Heparin Modification of Biomaterials to Reduce Thrombogenicity
Heparin Modification of Biomaterials for Drug Delivery
Immobilization of Heparin on Biomaterials for Drug Delivery
13.12 Concluding Remarks
Problems
References
Further Reading
14 Degradation of Metallic and Ceramic Biomaterials
14.1 Introduction
14.2 Corrosion of Metals
14.2.1 Principles of Metal Corrosion
Example 14.1
Solution:
Cathode Reactions
Example of Metal Corrosion: Iron
14.2.2 Rate of Corrosion
14.2.3 Pourbaix Diagrams
14.2.4 Types of Electrochemical Corrosion
Compositional Effects
Mechanical Stress Effects
Concentration Effects
14.3 Corrosion of Metal Implants in the Physiological Environment
14.3.1 Minimizing Metal Implant Corrosion in vivo
14.4 Degradation of Ceramics
14.4.1 Degradation by Dissolution and Disintegration
14.4.2 Cell‐Mediated Degradation
14.5 Concluding Remarks
Problems
References
Further Readings
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 Degradation
15.4.4 Oxidative Degradation of Polymeric Biomaterials
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
Further Readings
16 Biocompatibility Fundamentals. 16.1 Introduction
16.2 Biocompatibility Phenomena with Implanted Devices
16.2.1 Consequences of Failed Biocompatibility
Fully Resolvable Complications
Partially Resolvable Complications
Unresolvable Pathologies Associated with Failed Biocompatibility
Mortality Linked with Failed Biocompatibility
16.2.2 Basic Pattern of Biocompatibility Processes
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
16.4.6 Cell Contacts and Membrane Receptors
16.5 Extracellular Matrix and Tissues. 16.5.1 Components of the Extracellular Matrix
16.5.2 Attachment Factors
16.5.3 Cell Adhesion Molecules
16.5.4 Molecular and Physical Factors in Cell Attachment
16.5.5 Tissue Types and Origins
Epithelium
Connective Tissues
Embryo Layers and Tissue Origins
Tissues, Growth Factors and Cytokines
16.6 Plasma and Blood Cells
16.6.1 Erythrocytes
16.6.2 Leukocytes
16.7 Platelet Adhesion to Biomaterial Surfaces
16.8 Platelets and the Coagulation Process
16.9 Cell Types and Their Roles in Biocompatibility Phenomena
16.10 Concluding Remarks
Problems
References
Further Reading
17 Mechanical Factors in Biocompatibility Phenomena. 17.1 Introduction
17.2 Stages and Mechanisms of Mechanotransduction
17.2.1 Force Transduction Pathways
Focal Adhesions
Mechano‐Sensitive Ion Channels
17.2.2 Signal Transduction Pathways and Other Mechanisms
MAPK and Rho/ROCK Signal Transduction Pathways
LINC Proteins
17.2.3 Mechanisms of Cellular Response
Focal Adhesion Strengthening
Cell Migration
Extracellular Matrix Adjustments to Maintain Homeostasis
Gene Expression Responses
Osteoblasts
Endothelium
Tendon
Fibroblasts
17.3 Mechanical Stress‐Induced Biocompatibility Phenomena
17.3.1 Implantable Devices in Bone Healing
17.3.2 Implantable Devices in the Cardiovascular System
Vascular Grafts
Cardiac Remodeling
17.3.3 Soft Tissue Healing
Reduction of Peritoneal Fibrosis and Adhesions
Control of Scar Formation and Contractures
17.3.4 Stem Cells in Tissue Engineering
Scaffolds with Adjustable Stiffness for Engineering of Tissues
Cyclic Stretching in Stem Cell Engineering of Tissues
17.4 Outcomes of Transduction of Extracellular Stresses and Responses
17.5 Concluding Remarks
Problems
References
Further Reading
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 Reactive Oxygen Species
18.4.3 Phagocytosis by Neutrophils
18.4.4 Neutrophil Extracellular Traps (NETs)
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
Further Reading
19 Immune Responses to Biomaterials. 19.1 Introduction
19.2 Adaptive Immune System
19.2.1 Lymphocyte Origins of Two Types of Adaptive 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‐Based Biomaterials and Complexes
19.5 Designing Biomaterials to Modulate Immune Responses
19.6 Concluding Remarks
Problems
References
Glossary
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 Implant Surface
20.4.2 Specific Irreversible Attachment of Bacteria 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 Effect of Biomaterial Characteristics on Bacterial Adhesion
20.6 Biofilm Shielding of Infection from Host Defenses and Antibiotics
20.7 Effects of Biofilm 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
Further Reading
21 Response to Surface Topography and Particulate Materials. 21.1 Introduction
21.2 of Biomaterial Surface Topography on Cell Response
21.2.1 Microscale Surface Topography in Osseointegration
21.2.2 Microscale and Nanoscale Patterned Surfaces in Macrophage Differentiation
21.2.3 Microscale Patterned Surfaces in Neural Regeneration
21.3 Biomaterial Surface Topography for Antimicrobial Activity
21.3.1 Microscale Topography with Antimicrobial Activity
21.3.2 Nanoscale Topography with Antimicrobial Activity
Nanoscale Surface Parameters
Mechanism of Bactericidal Activity
Effect of Nanoscale Surface Parameters on Bactericidal Activity
21.4 Microparticle‐Induced Host Responses
21.4.1 Mechanisms of Microparticle Endocytosis
21.4.2 Response to Microparticles
Effect of Microparticle Size
Effect of Microparticle Shape
Effect of Microparticle Composition
Effect of Microparticle Mechanical Properties
21.4.3 Microparticle Distribution in the Organs
21.4.4 The Inflammasome and Microparticle‐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
Effect of Nanoparticle Size
Effect of Nanoparticle Shape
Effect of Nanoparticle Surface Composition
21.5.3 Cytotoxicity Effects of Nanoparticles
21.6 Concluding Remarks
Problems
References
Further Readings
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
Direct Contact Assay
Agarose Overlay Test
MTT Assay
Live/Dead Cell Staining
22.3.2 Genotoxicity Tests. The Ames Test
Mammalian Genotoxicity Tests
22.3.3 Hemocompatibility Tests
Complement Activation C3a and SC5b Assay
Platelets
Coagulation
Blood Cell Numbers and Hemolysis
Blood Flow Loop
22.4 In vivo Biocompatibility Test Procedures
22.4.1 Implantation Tests
Subcutaneous Implantation Tests
Intramuscular Implantation Tests
Bone Implantation Tests In Vivo
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 FDA Review and Approval
22.7 Case Study: The Proplast Temporomandibular Joint
22.8 Concluding Remarks
Problems
References
Further Reading
23 Biomaterials for Hard Tissue Repair. 23.1 Introduction
23.2 Healing of Bone Fracture
23.2.1 Mechanism of Fracture Healing
Hematoma Formation
Soft Callus Formation
Bony Callus Formation
Bone Remodeling
23.2.2 Internal Fracture Fixation Devices
23.3 Healing of Bone Defects
23.3.1 Bone Defects
23.3.2 Bone Grafts
Bone Autografts
Bone Allografts
23.3.3 Bone Graft Substitutes
Ceramic‐Based Bone Graft Substitutes
Polymer‐Based Bone Graft Substitutes
Metal‐Based Bone Graft Substitutes
Composite Bone Graft Substitutes
Combination of Biomaterials with Cells and Growth Factors
23.3.4 Healing of Nonstructural 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 Direct Dental Restorations
23.6.3 Indirect Dental Restorations
Metal‐Ceramic Dental Restorations
Glass‐Ceramic Dental Restorations
Polycrystalline Ceramic Dental Restorations
23.7 Concluding Remarks
Problems
References
Further Reading
24 Biomaterials for Soft Tissue Repair. 24.1 Introduction
24.2 Surgical Sutures and Adhesives
24.2.1 Sutures
Types of Sutures
Degradable Sutures
24.2.2 Soft Tissue Adhesives
24.3 The Cardiovascular System
24.3.1 The Heart
24.3.2 The Circulatory System
24.4 Vascular Grafts
24.4.1 Desirable Properties and Characteristics of Synthetic Vascular Grafts
24.4.2 Synthetic Vascular Graft Materials
24.4.3 Patency of Vascular Grafts
Influence of the Mechanical Properties of the Graft
Influence of the Composition and Nature of the Graft
24.5 Balloon Angioplasty
24.6 Intravascular Stents
24.6.1 Bare‐Metal Stents
24.6.2 Drug‐Eluting Stents
24.6.3 Degradable Stents
24.7 Prosthetic Heart Valves
24.7.1 Mechanical Valves
24.7.2 Bioprosthetic Valves
Performance of Heart Valves
24.8 Ophthalmologic Applications
24.8.1 Contact Lenses
Soft Contact Lens Materials
Performance of Contact Lenses
24.8.2 Intraocular Lenses
Intraocular Lens Materials
Biocompatibility of Intraocular Lenses
24.9 Skin Wound Healing
24.9.1 Skin Wound Healing Fundamentals
Hemostasis
Inflammation
Proliferation
Remodeling
24.9.2 Complicating Factors in Skin Wound Healing
24.9.3 Biomaterials‐Based Therapies
Therapies Based on the Use of Biomaterials Alone
Biomaterials in Combination with Biomolecules
Biomaterials in Combination with Cells
24.9.4 Nanoparticle‐Based Therapies
24.10 Concluding Remarks
Problems
References
Further Reading
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
Differentiated Cells
Cells with Differentiation Potential
Induced Pluripotent Cells
25.2.2 Biomolecules and Nutrients for in vitro Cell Culture
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
Porous Solids Composed of Synthetic Polymers
Porous Solids Composed of Natural Polymers
Copolymers, Blends, and Composites
Porous Solids Composed of Ceramics
25.3.4 Hydrogels
25.3.5 Extracellular Matrix (ECM) Scaffolds
25.4 Creation of Scaffolds for Tissue Engineering
25.4.1 Creation of Scaffolds in the Form of Porous Solids
Thermal Bonding of Particles
Use of a Pore‐forming Agent
Foaming Techniques
Polymer Foam Replication
Freezing Techniques
25.4.2 Electrospinning
Principles of the Electrospinning Process
Parameters and Variations of the Electrospinning Process
Electrospun Scaffolds for Tissue Engineering
25.4.3 Additive Manufacturing (3D Printing) Techniques
Fused Deposition Modeling
Selective Laser Sintering
Stereolithography
Robocasting
Inkjet Printing
25.4.4 Formation of Hydrogel Scaffolds
25.4.5 Preparation of Extracellular Matrix (ECM) Scaffolds
25.5 Three‐dimensional Bioprinting
25.5.1 Inkjet‐Based Bioprinting
25.5.2 Microextrusion‐Based Bioprinting
25.6 Tissue Engineering Techniques for the Regeneration of Functional Tissues and Organs
25.6.1 Bone Tissue Engineering
25.6.2 Articular Cartilage Tissue Engineering
Composition, Structure, and Function of Articular Cartilage
Biomaterials and Strategies in Cartilage Tissue Engineering
25.6.3 Tissue Engineering of Articular Joints
25.6.4 Tissue Engineering of Tendons and Ligaments
Structure and Function of Tendons and Ligaments
Biomaterials and Strategies for Tendon and Ligament Tissue Engineering
25.6.5 Skin Tissue Engineering
Tissue‐engineered Skin Substitutes
25.6.6 Bladder Tissue Engineering
25.7 Concluding Remarks
Problems
References
Further Reading
26 Biomaterials for Drug Delivery. 26.1 Introduction
26.2 Controlled Drug Release
26.2.1 Drug Delivery Systems
26.2.2 Mechanisms of Drug Release
Release by Diffusion
Release by Erosion
Release by Cleavage of Chemical Bonds
Release by Osmosis
26.3 Designing Biomaterials for Drug Delivery Systems
26.4 Microparticle‐based Delivery Systems
26.4.1 Preparation of Polymer Microsphere Delivery Systems
26.4.2 Applications of Microparticle Delivery Systems
26.5 Hydrogel‐based Delivery Systems
26.5.1 Environmentally Responsive Drug Delivery Systems
pH Responsive Hydrogels
Temperature Responsive Hydrogels
26.5.2 Drug Delivery Systems Responsive to External Physical Stimuli
Acoustic Stimulated Drug Delivery
Magnetic Stimulated Drug Delivery
26.6 Nanoparticle‐based Delivery Systems
26.6.1 Distribution and Fate of Nanoparticle‐based Drug Delivery Systems
26.6.2 Targeting of Nanoparticles to Cells
Tumor Vasculature and Microenvironment
Passive Targeting
Active Targeting
Antibody Ligands
Aptamers
Small Molecule Targeting
26.6.3 Polymer‐based Nanoparticle Systems
26.6.4 Lipid‐based Nanoparticle Systems
Liposomes
Lipid–Polymer Hybrid Nanoparticles
Polymersomes
Micelles
26.6.5 Polymer Conjugates
Polymer–Protein Conjugates
Polymer–Drug Conjugates
26.6.6 Dendrimers
26.6.7 Inorganic Nanoparticles
26.7 Delivery of Ribonucleic Acid (RNA)
26.7.1 Chemical Modification of siRNA
26.7.2 Biomaterials for siRNA Delivery
Lipid‐based Delivery Systems
Polymer‐based Nanoparticle Delivery Systems
Inorganic Nanoparticles for siRNA Delivery
26.8 Biological Drug Delivery Systems
26.8.1 Exosomes for Therapeutic Biomolecule Delivery
26.9 Concluding Remarks
Problems
References
Further Reading
Index. a
b
c
d
e
f
g
h
i
j
k
l
m
n
o
p
q
r
s
t
u
v
w
x
y
z
WILEY END USER LICENSE AGREEMENT
