Biomaterials: The Intersection of Biology and Materials Science

Cover
Contents
Foreword
Preface
Acknowledgments
1 Materials for Biomedical Applications
	1.1 Introduction to Biomaterials
		1.1.1 Important Definitions
		1.1.2 History and Current Status of the Field
		1.1.3 Future Directions
	1.2 Biological Response to Biomaterials
	1.3 Biomaterial Product Testing and FDA Approval
	1.4 Types of Biomaterials
		1.4.1 Metals
		1.4.2 Ceramics
		1.4.3 Polymers
		1.4.4 Naturally Derived vs. Synthetic Polymers
	1.5 Processing of Biomaterials
	1.6 Important Properties of Biomaterials
		1.6.1 Degradative Properties of Biomaterials
		1.6.2 Surface Properties of Biomaterials
		1.6.3 Bulk Properties of Biomaterials
		1.6.4 Characterization Techniques
	1.7 Principles of Chemistry
		1.7.1 Atomic Structure
		1.7.2 Atomic Models
		1.7.3 Atomic Orbitals
		1.7.4 Valence Electrons and the Periodic Table
		1.7.5 Ionic Bonding
		1.7.6 Covalent Bonding
		1.7.7 Metallic Bonding
		1.7.8 Secondary Forces
	Summary
	Problems
	References
	Additional Reading
2 Chemical Structure of Biomaterials
	2.1 Introduction: Bonding and the Structure of Biomaterials
	2.2 Structure of Metals
		2.2.1 Crystal Structures
		2.2.2 Crystal Systems
		2.2.3 Defects in Crystal Structures
		2.2.4 Solid State Diffusion
	2.3 Structure of Ceramics
		2.3.1 Crystal Structures
		2.3.2 Defects in Crystal Structures
	2.4 Structure of Polymers
		2.4.1 General Structure
		2.4.2 Polymer Synthesis
		2.4.3 Copolymers
		2.4.4 Methods of Polymerization
		2.4.5 Crystal Structures and Defects
	2.5 Techniques: Introduction to Material Characterization
		2.5.1 X-Ray Diffraction
		2.5.2 Ultraviolet and Visible Light Spectroscopy (UV-VIS)
		2.5.3 Infrared Spectroscopy (IR)
		2.5.4 Nuclear Magnetic Resonance Spectroscopy (NMR)
		2.5.5 Mass Spectrometry
		2.5.6 High-Performance Liquid Chromatography (HPLC): Size-Exclusion Chromatography
	Summary
	Problems
	References
	Additional Reading
3 Physical Properties of Biomaterials
	3.1 Introduction: From Atomic Groupings to Bulk Materials
	3.2 Crystallinity and Linear Defects
		3.2.1 Dislocations
		3.2.2 Deformation
	3.3 Crystallinity and Planar Defects
		3.3.1 External Surface
		3.3.2 Grain Boundaries
	3.4 Crystallinity and Volume Defects
	3.5 Crystallinity and Polymeric Materials
		3.5.1 Percent Crystallinity
		3.5.2 Chain-Folded Model of Crystallinity
		3.5.3 Defects in Polymer Crystals
	3.6 Thermal Transitions of Crystalline and Non-Crystalline Materials
		3.6.1 Viscous Flow
		3.6.2 Thermal Transitions
	3.7 Techniques: Introduction to Thermal Analysis
		3.7.1 Differential Scanning Calorimetry
	Summary
	Problems
	References
	Additional Reading
4 Mechanical Properties of Biomaterials
	4.1 Introduction: Modes of Mechanical Testing
	4.2 Mechanical Testing Methods, Results and Calculations
		4.2.1 Tensile and Shear Properties
		4.2.2 Bending Properties
		4.2.3 Time-Dependent Properties
		4.2.4 Influence of Porosity and Degradation on Mechanical Properties
	4.3 Fracture and Failure
		4.3.1 Ductile and Brittle Fracture
		4.3.2 Polymer Crazing
		4.3.3 Stress Concentrators
	4.4 Fatigue and Fatigue Testing
		4.4.1 Fatigue
		4.4.2 Fatigue Testing
		4.4.3 Factors that Affect Fatigue Life
	4.5 Methods to Improve Mechanical Properties
	4.6 Techniques: Introduction to Mechanical Analysis
		4.6.1 Mechanical Testing
	Summary
	Problems
	References
	Additional Reading
5 Biomaterial Degradation
	5.1 Introduction: Degradation in the Biological Environment
	5.2 Corrosion/Degradation of Metals and Ceramics
		5.2.1 Fundamentals of Corrosion
		5.2.2 Pourbaix Diagrams and Passivation
		5.2.3 Contribution of Processing Parameters
		5.2.4 Contribution of the Mechanical Environment
		5.2.5 Contribution of the Biological Environment
		5.2.6 Means of Corrosion Control
		5.2.7 Ceramic Degradation
	5.3 Degradation of Polymers
		5.3.1 Primary Means of Polymer Degradation
		5.3.2 Chain Scission by Hydrolysis
		5.3.3 Chain Scission by Oxidation
		5.3.4 Other Means of Degradation
		5.3.5 Effects of Porosity
	5.4 Biodegradable Materials
		5.4.1 Biodegradable Ceramics
		5.4.2 Biodegradable Polymers
	5.5 Techniques: Assays for Extent of Degradation
	Summary
	Problems
	References
	Additional Reading
6 Biomaterial Processing
	6.1 Introduction: Importance of Biomaterials Processing
	6.2 Processing to Improve Bulk Properties
		6.2.1 Metals
		6.2.2 Ceramics
		6.2.3 Polymers
	6.3 Processing to Form Desired Shapes
	6.4 Processing of Metals
		6.4.1 Forming Operations
		6.4.2 Casting Metals
		6.4.3 Powder Processing of Metals
		6.4.4 Rapid Manufacturing of Metals
		6.4.5 Welding Metals
		6.4.6 Machining of Metals
	6.5 Processing of Ceramics
		6.5.1 Glass Forming Techniques
		6.5.2 Casting and Firing of Ceramics
		6.5.3 Powder Processing of Ceramics
		6.5.4 Rapid Manufacturing of Ceramics
	6.6 Processing of Polymers
		6.6.1 Thermoplasts vs. Thermosets
		6.6.2 Forming Polymers
		6.6.3 Casting Polymers
		6.6.4 Rapid Manufacturing of Polymers
	6.7 Processing to Improve Biocompatibility
		6.7.1 Sterilization
		6.7.2 Fixation of Natural Materials
	Summary
	Problems
	References
	Additional Reading
7 Surface Properties of Biomaterials
	7.1 Introduction: Concepts in Surface Chemistry and Biology
		7.1.1 Protein Adsorption and Biocompatibility
		7.1.2 Surface Properties Governing Protein Adsorption
	7.2 Physicochemical Surface Modification Techniques
		7.2.1 Introduction to Surface Modification Techniques
		7.2.2 Physicochemical Surface Coatings: Covalent Surface Coatings
		7.2.3 Physicochemical Surface Coatings: Non-Covalent Surface Coatings
		7.2.4 Physicochemical Surface Modification Methods with No Overcoat
		7.2.5 Laser Methods for Surface Modification
	7.3 Biological Surface Modification Techniques
		7.3.1 Covalent Biological Coatings
		7.3.2 Non-Covalent Biological Coatings
		7.3.3 Immobilized Enzymes
	7.4 Surface Properties and Degradation
	7.5 Patterning Techniques for Surfaces
	7.6 Techniques: Introduction to Surface Characterization
		7.6.1 Contact Angle Analysis
		7.6.2 Light Microscopy
		7.6.3 Electron Spectroscopy for Chemical Analysis (ESCA) or X-ray Photoelectron Spectroscopy (XPS)
		7.6.4 Attenuated Total Internal Reflectance Fourier Transform––Infrared Spectroscopy (ATR-FTIR)
		7.6.5 Secondary Ion Mass Spectrometry (SIMS)
		7.6.6 Electron Microscopy: Transmission Electron Microscopy (TEM) and Scanning Electron Microscopy (SEM)
		7.6.7 Scanning Probe Microscopy (SPM): Atomic Force Microscopy (AFM)
	Summary
	Problems
	References
	Additional Reading
8 Protein Interactions with Biomaterials
	8.1 Introduction: Thermodynamics of Protein Adsorption
		8.1.1 Gibbs Free Energy and Protein Adsorption
		8.1.2 System Properties Governing Protein Adsorption
	8.2 Protein Structure
		8.2.1 Amino Acid Chemistry
		8.2.2 Primary Structure
		8.2.3 Secondary Structure
		8.2.4 Tertiary Structure
		8.2.5 Quaternary Structure
	8.3 Protein Transport and Adsorption Kinetics
		8.3.1 Transport to the Surface
		8.3.2 Adsorption Kinetics
	8.4 Reversibility of Protein Adsorption
		8.4.1 Reversible and Irreversible Binding
		8.4.2 Desorption and Exchange
	8.5 Techniques: Assays for Protein Type and Amount
		8.5.1 High-Performance Liquid Chromatography (HPLC): Affinity Chromatography
		8.5.2 Colorimetric Assays
		8.5.3 Fluorescent Assays
		8.5.4 Enzyme-linked Immunosorbent Assay (ELISA)
		8.5.5 Western Blotting
	Summary
	Problems
	References
	Additional Reading
9 Cell Interactions with Biomaterials
	9.1 Introduction: Cell-Surface Interactions and Cellular Functions
	9.2 Cellular Structure
		9.2.1 Cell Membrane
		9.2.2 Cytoskeleton
		9.2.3 Mitochondria
		9.2.4 Nucleus
		9.2.5 Endoplasmic Reticulum
		9.2.6 Vesicles
		9.2.7 Membrane Receptors and Cell Contacts
	9.3 Extracellular Environment
		9.3.1 Collagen
		9.3.2 Elastin
		9.3.3 Proteoglycans
		9.3.4 Glycoproteins
		9.3.5 Other ECM Components
		9.3.6 Matrix Remodeling
		9.3.7 ECM Molecules as Biomaterials
	9.4 Cell–Environment Interactions that Affect Cellular Functions
		9.4.1 Cell Survival
		9.4.2 Cell Proliferation
		9.4.3 Cell Differentiation
		9.4.4 Protein Synthesis
	9.5 Models of Adhesion, Spreading and Migration
		9.5.1 Basic Adhesion Models: DLVO Theory
		9.5.2 DLVO Theory Limitations and Further Models
		9.5.3 Models of Cell Spreading and Migration
	9.6 Techniques: Assays to Determine Effects of Cell-Material Interactions
		9.6.1 Cytotoxicity Assays
		9.6.2 Adhesion/Spreading Assays
		9.6.3 Migration Assays
		9.6.4 DNA and RNA Assays
		9.6.5 Protein Production Assays: Immunostaining
	Summary
	Problems
	References
	Additional Reading
10 Biomaterial Implantation and Acute Inflammation
	10.1 Introduction: Overview of Innate and Acquired Immunity
		10.1.1 Characteristics of Leukocytes
		10.1.2 Sources of Innate Immunity
	10.2 Clinical Signs of Inflammation and Their Causes
	10.3 Role of Tissue Macrophages and Neutrophils
		10.3.1 Migration of Neutrophils
		10.3.2 Actions of Neutrophils
	10.4 Role of Other Leukocytes
		10.4.1 Monocytes/Macrophages
		10.4.2 Actions of Macrophages
		10.4.3 Other Granulocytes
	10.5 Termination of Acute Inflammation
	10.6 Techniques: In Vitro Assays for Inflammatory Response
		10.6.1 Leukocyte Assays
		10.6.2 Other Assays
	Summary
	Problems
	References
	Additional Reading
11 Wound Healing and the Presence of Biomaterials
	11.1 Introduction: Formation of Granulation Tissue
	11.2 Foreign Body Reaction
	11.3 Fibrous Encapsulation
	11.4 Chronic Inflammation
	11.5 Four Types of Resolution
	11.6 Repair vs. Regeneration: Wound Healing in Skin
		11.6.1 Skin Repair
		11.6.2 Skin Regeneration
	11.7 Techniques: In Vivo Assays for Inflammatory Response
		11.7.1 Considerations in Development of Animal Models
		11.7.2 Methods of Assessment
	Summary
	Problems
	References
	Additional Reading
12 Immune Response to Biomaterials
	12.1 Introduction: Overview of Acquired Immunity
	12.2 Antigen Presentation and Lymphocyte Maturation
		12.2.1 Major Histocompatibility Complex (MHC) Molecules
		12.2.2 Maturation of Lymphocytes
		12.2.3 Activation and Formation of Clonal Populations
	12.3 B Cells and Antibodies
		12.3.1 Types of B Cells
		12.3.2 Characteristics of Antibodies
	12.4 T Cells
		12.4.1 Types of T Cells
		12.4.2 Helper T Cells (T[sub(h)])
		12.4.3 Cytotoxic T Cells (T[sub(c)])
	12.5 The Complement System
		12.5.1 Classical Pathway
		12.5.2 Alternative Pathway
		12.5.3 Membrane Attack Complex
		12.5.4 Regulation of the Complement System
		12.5.5 Effects of the Complement System
	12.6 Undesired Immune Responses to Biomaterials
		12.6.1 Innate vs. Acquired Responses to Biomaterials
		12.6.2 Hypersensitivity
	12.7 Techniques: Assays for Immune Response
		12.7.1 In Vitro Assays
		12.7.2 In Vivo Assays
	Summary
	Problems
	References
	Additional Reading
13 Biomaterials and Thrombosis
	13.1 Introduction: Overview of Hemostasis
	13.2 Role of Platelets
		13.2.1 Platelet Characteristics and Functions
		13.2.2 Platelet Activation
	13.3 Coagulation Cascade
		13.3.1 Intrinsic Pathway
		13.3.2 Extrinsic Pathway
		13.3.3 Common Pathway
	13.4 Means of Limiting Clot Formation
	13.5 Role of the Endothelium
	13.6 Tests for Hemocompatibility
		13.6.1 General Testing Concerns
		13.6.2 In Vitro Assessment
		13.6.3 In Vivo Assessment
	Summary
	Problems
	References
	Additional Reading
14 Infection, Tumorigenesis and Calcification of Biomaterials
	14.1 Introduction: Overview of Other Potential Problems with Biomaterial Implantation
	14.2 Infection
		14.2.1 Common Pathogens and Categories of Infection
		14.2.2 Steps to Infection
		14.2.3 Characteristics of the Bacterial Surface, the Biomaterial Surface, and the Media
		14.2.4 Specific and Non-Specific Interactions Involved in Bacterial Adhesion
		14.2.5 Summary of Implant-Associated Infections
	14.3 Techniques for Infection Experiments
		14.3.1 Characterizing Bacterial Surfaces
		14.3.2 In Vitro and In Vivo Models of Infection
	14.4 Tumorigenesis
		14.4.1 Definitions and Steps of Tumorigenesis
		14.4.2 Chemical vs. Foreign Body Carcinogenesis
		14.4.3 Timeline for Foreign Body Tumorigenesis
		14.4.4 Summary of Biomaterial-Related Tumorigenesis
	14.5 Techniques for Tumorigenesis Experiments
		14.5.1 In Vitro Models
		14.5.2 In Vivo Models
	14.6 Pathologic Calcification
		14.6.1 Introduction to Pathologic Calcification
		14.6.2 Mechanism of Pathologic Calcification
		14.6.3 Summary and Techniques to Reduce Pathologic Calcification
	14.7 Techniques for Pathologic Calcification Experiments
		14.7.1 In Vitro Models of Calcification
		14.7.2 In Vivo Models of Calcification
		14.7.3 Sample Assessment
	Summary
	Problems
	References
	Additional Reading
Appendix I: List of Abbreviations and Symbols
Index
	A
	B
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	D
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	H
	I
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	N
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	Q
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