Handbook of Biomaterials Biocompatibility (Woodhead Publishing Series in Biomaterials)

Cover
HANDBOOK OF
BIOMATERIALS
BIOCOMPATIBILITY
Copyright
Contents
List of Contributors
Preface
Acknowledgments
Sec1
1 Principles of biocompatibility
	1.1 Introduction
	1.2 Conclusion
	References
	Further reading
2 Bacterial cell–biomaterials interactions
	2.1 Introduction
	2.2 Theoretical theories of bacterial adhesion to biomaterial surfaces
	2.3 Factors influencing bacterial adhesion to biomaterial surfaces
		2.3.1 Biomaterial surface properties
		2.3.2 Plasma proteins
		2.3.3 Platelets
		2.3.4 Fluid flow
	2.4 Bacterial interaction with antibacterial biomaterial surfaces
	2.5 Signaling molecules in the regulation of bacterial adhesion on biomaterial surfaces
	2.6 Summary and perspectives
	References
3 Macrophage response to biomaterials
	3.1 The macrophage
	3.2 Macrophage plasticity and polarization
	3.3 The macrophage response to biomaterials
	3.4 The macrophages and the development of immunomodulatory biomaterials
		3.4.1 Immunomodulatory biomaterials
		3.4.2 Macrophages in immunomodulation
	References
4 Dendritic cells responses to biomaterials
	4.1 Introduction
	4.2 Natural polymer biomaterials
	4.3 Gelatin
	4.4 Alginate
	4.5 Chitosan
	4.6 Synthetic polymer biomaterials
	4.7 Poly(lactic-co-glycolic acid)
	4.8 Polyethylene glycol
	4.9 Blends
	4.10 Poly(lactic-co-glycolic acid)-chitosan
		4.10.1 Monomethoxy poly(ethylene glycol)-poly(lactic-co-glycolic acid)
	4.11 Conclusion and future directions
	References
5 Impact of biomaterials’ physical properties on cellular and molecular responses
	Abbreviations
	5.1 Introduction
	5.2 Cellular and molecular response following implantation
		5.2.1 Blood-materials interaction
		5.2.2 Acute inflammation
		5.2.3 Chronic inflammation
		5.2.4 Wound healing
		5.2.5 Foreign body reaction
		5.2.6 Fibrous capsule formation
	5.3 Impact of physical properties on modulation of the host response
		5.3.1 Size
		5.3.2 Configuration and topography
		5.3.3 Stiffness
		5.3.4 Surface chemistry
	5.4 Conclusion
	References
6 Impact of biomaterial mechanics on cellular and molecular responses
	6.1 Introduction
	6.2 Host response—biomaterial interplay
		6.2.1 Phase I
		6.2.2 Phase II
		6.2.3 Phase III
		6.2.4 Phase IV
		6.2.5 Phase V
	6.3 Other significant players of the foreign body reaction
	6.4 Impact of biomaterial surface characteristics on the sequential phases of host response
		6.4.1 On protein adsorption
		6.4.2 On acute inflammation
		6.4.3 On chronic inflammation
		6.4.4 On foreign body giant cell formation
		6.4.5 On capsule formation and fibrosis
	6.5 Conclusion
	Conflict of interest
	References
7 Cell–biomaterials interactions: the role of growth factors
	7.1 Introduction
	7.2 What are growth factors?
	7.3 Growth factors in bone tissue engineering
	7.4 Bone morphogenetic proteins
	7.5 Transforming growth factor βs
	7.6 Platelet-derived growth factors
	7.7 Fibroblast growth factors
	7.8 Insulin-like growth factors
	7.9 Bone growth factors clinical applications
	7.10 Conclusion and perspectives
	Conflict of interest
	References
8 Cell–biomaterial interactions: the role of ligand functionalization
	8.1 Introduction
	8.2 Ligand functionalization in the design of bioactive hydrogels
		8.2.1 General functionalization strategies for hydrogels
		8.2.2 Peptide functionalization of hydrogels for cardiac tissue engineering
	8.3 Ligand surface functionalization in the design of scaffolds and implants
	8.4 Ligand functionalization of nanoparticles for cell targeting
	8.5 General discussion and conclusion
	References
9 On the proliferation of cell proliferation tests
	9.1 Introduction
		9.1.1 The need and challenge of assessing cell proliferation on biomaterials
		9.1.2 Cell proliferation versus cell viability
	9.2 Methods to measure cell proliferation
		9.2.1 Metabolism-based assays
			9.2.1.1 MTT
			9.2.1.2 Other tetrazolium salts
				WST-1
				XTT
				MTS
				CCK8
		9.2.2 alamarBlue
		9.2.3 Nucleic acid-based assays
			9.2.3.1 PicoGreen and CyQUANT
			9.2.3.2 Thymidine analogues
		9.2.4 Other methods
			9.2.4.1 Adenosine triphosphate
			9.2.4.2 Immunofluoresence markers
			9.2.4.3 Nuclei counting
			9.2.4.4 Hemacytometer
			9.2.4.5 Transepithelial/transendothelial electrical resistance
			9.2.4.6 Flow cytometry
	9.3 Comparison of proliferation tests
	9.4 Special challenges and experimental design considerations
		9.4.1 Cell seeding and proliferation in three-dimensional scaffolds
		9.4.2 Cell density
		9.4.3 Bioactive materials
		9.4.4 Controls
	9.5 Conclusion
	References
10 In vivo models for biomaterials: applications from cardiovascular tissue engineering
	Abbreviations
	10.1 Introduction
	10.2 Constructs and biomaterials used in cardiac tissue engineering
		10.2.1 Materials for cell delivery to cardiac tissue
		10.2.2 Cardiac tissue patches
			10.2.2.1 Decellularized materials
			10.2.2.2 Electrically conductive materials
		10.2.3 Construct performance in vivo
			10.2.3.1 Material degradation
			10.2.3.2 Immunogenicity: macrophage infiltration
			10.2.3.3 Neovasculature and angiogenesis
		10.2.4 Scarring and arrhythmogenesis
			10.2.4.1 Assessment of arrhythmogenicity
			10.2.4.2 Arrhythmogenicity of biomaterials
			10.2.4.3 Mitigating the risk of arrhythmogenesis
		10.2.5 Challenges of biomaterials used in cardiac tissue engineering
	10.3 Constructs and biomaterials used in vascular tissue engineering
		10.3.1 Biomaterials used in vascular tissue engineering
		10.3.2 Fabrication methods
		10.3.3 Construct performance in vivo
			10.3.3.1 Blood clots
			10.3.3.2 Vessel integrity and aneurysm formation
			10.3.3.3 Immunogenicity
	10.4 In vivo applications of constructs and biomaterials
	10.5 Conclusion
	References
11 Clinical and surgical aspects of medical materials’ biocompatibility
	Author disclosure statement
	Abbreviations
	11.1 Introduction
	11.2 Orthopedic biomaterials
		11.2.1 Fracture fixation applications
		11.2.2 Joint replacement applications
		11.2.3 Graft applications (auto-, allo-, xeno-)
		11.2.4 Synthetic grafts and filling material applications
	11.3 General and reconstructive surgery biomaterials
		11.3.1 Injectable biomaterials
		11.3.2 Reconstructive breast surgery and breast implants
		11.3.3 Hernia repair and mesh materials
	11.4 Cardiovascular biomaterials
		11.4.1 Coronary stents
		11.4.2 Heart valves
		11.4.3 Implantable pacemakers
		11.4.4 Left ventricular assist devices
		11.4.5 Vascular grafts
	11.5 Conclusion
	References
12 Standardization and regulation of biomaterials
	12.1 Introduction
	12.2 Biomaterials for therapeutic and regenerative medicine
		12.2.1 Biomaterial design, fabrication, characterization, and documentation
		12.2.2 In vitro cellular response analysis for biomaterials study
		12.2.3 In vivo animal model for biomaterials study
	12.3 Discussion
		12.3.1 Standardization of experimental protocols
		12.3.2 Biomaterial regulations and policies
		12.3.3 Translation and society
		12.3.4 Medico-legal and health insurance systems
	12.4 Conclusion
	References
Sec2
13 Cellular response to synthetic polymers
	Abbreviations
	13.1 Introduction
	13.2 Cellular response to synthetic nondegradable polymers
		13.2.1 Poly(ethylene), poly(methyl methacrylate), and poly(tetrafluoroethylene) in bone regeneration
			13.2.1.1 Inflammatory changes preceding osteolysis
			13.2.1.2 Osteolysis
		13.2.2 Poly(propylene), poly(tetrafluoroethylene), and poly(ethylene terephthalate) as surgical meshes
			13.2.2.1 Biologic response to mesh
		13.2.3 Cellular response to synthetic polymers used in cardiac surgery
			13.2.3.1 Poly(vinyl chloride), poly(tetrafluoroethylene), poly(urethane), and poly(ethylene) as catheters in cardiac surgery
			13.2.3.2 Poly(ethylene terephthalate) and poly(tetrafluoroethylene) used in cardiac surgery
		13.2.4 Cellular response to poly(methyl methacrylate)
		13.2.5 Cellular response to poly(urethane) and poly(amides) (nylon)
		13.2.6 Cellular response to poly(styrene)
			13.2.6.1 Poly(styrene) as a cell culture material
			13.2.6.2 Surface functionalization by liquid treatment
			13.2.6.3 Surface functionalization by plasma treatment
			13.2.6.4 Surface functionalization by other methods
		13.2.7 Cellular response to other synthetic polymers
			13.2.7.1 Poly(sulfone)
			13.2.7.2 Polyethersulfone
			13.2.7.3 Poly(etherimide)
			13.2.7.4 Poly(etheretherketone)
	13.3 Cellular response to biodegradable/resorbable polymers
		13.3.1 Cellular response to poly(lactic acid)
		13.3.2 Cellular response to polycarbonates
	13.4 Conclusion and future trends
	References
14 Cellular responses to zirconia
	14.1 Introduction
	14.2 “Aging” of zirconia
	14.3 Definitions of biocompatibility, osseointegration, osteoinductivity, and osteoconductivity
	14.4 In vitro zirconia biocompatibility
		14.4.1 Cellular response of the fibroblasts
		14.4.2 Cellular response of leukocyte cell lines
		14.4.3 Cellular response of osteoblasts and osteoclast
	14.5 In vivo zirconia biocompatibility
	14.6 Conclusion
	References
15 Cellular response to alumina
	15.1 Introduction
	15.2 Physicochemical properties of alumina surface
	15.3 Cellular responses and protein adsorption on alumina surface
	15.4 Futures and conclusion
	References
16 Biocompatibility of graphene quantum dots and related materials
	Abbreviations
	16.1 Introduction
	16.2 In vitro biocompatibility studies
		16.2.1 In vitro biocompatibility study of graphene quantum dot
		16.2.2 In vitro biocompatibility study of graphene derivatives
	16.3 In vivo biocompatibility studies
		16.3.1 In vivo biocompatibility study of graphene quantum dots
		16.3.2 In vivo biocompatibility study of graphene derivatives
	16.4 Biocompatibility study of other carbon nanostructures
		16.4.1 Biocompatibility study of carbon nanotube
		16.4.2 Biocompatibility study of fullerene
		16.4.3 Biocompatibility study of carbon dot
		16.4.4 Biocompatibility study of nanodiamond
	16.5 Approaches to reduce toxicity
		16.5.1 Green synthesis
		16.5.2 Coating/functionalization
	16.6 Conclusion
	References
17 Cellular response to calcium phosphate cements
	17.1 Introduction
	17.2 General characteristics of calcium phosphate cement
	17.3 Chemistry and handling
	17.4 Biological evaluation of calcium phosphate cements
	17.5 Biodegradation of calcium phosphate cements
	17.6 Bioactivity of calcium phosphate cements
	17.7 Osteoconductivity of calcium phosphate cements
	17.8 Osteoinductivity of calcium phosphate cements
	17.9 Cellular response to calcium phosphate cements
	17.10 Clinical applications
	References
18 Cellular response to bioactive glasses and glass–ceramics
	18.1 Introduction
	18.2 Biological responses to biomaterials
	18.3 Bioactive glasses and glass–ceramics: structure and their physicochemical properties
		18.3.1 Silicate-based glasses
		18.3.2 Borate-based glasses
		18.3.3 Phosphate-based glasses
	18.4 Innovative strategies for selective contribution of bioactive glasses
		18.4.1 Cellular and molecular behavior of bioactive glasses in response to different doped ions
			18.4.1.1 Fluoride-containing bioactive glasses
			18.4.1.2 Magnesium containing bioactive glasses
			18.4.1.3 Strontium containing bioactive glasses
			18.4.1.4 Silver-containing bioactive glasses
			18.4.1.5 Copper-containing bioactive glasses
			18.4.1.6 Zinc-containing bioactive glasses
			18.4.1.7 Cobalt-containing bioactive glasses
		18.4.2 Silanization
		18.4.3 Surface functionalization of bioactive glasses through biological approaches
	18.5 Commercialized bioactive glasses and glass–ceramics
	18.6 Discussion
	18.7 Conclusion
	References
19 Cell responses to titanium and titanium alloys
	19.1 Introduction
	19.2 Surface modification of titanium alloys to induce appropriate cell responses
		19.2.1 Repair and regeneration of hard tissues
			19.2.1.1 Surface topography and surface roughness
			19.2.1.2 Surface wettability and free energy
			19.2.1.3 Surface chemistry
				Inorganic coatings
				Organic coatings
		19.2.2 Repair and attachment of soft tissue
		19.2.3 Modulation of the immune response
	19.3 Antimicrobial coatings on titanium
		19.3.1 Coatings
			19.3.1.1 Antibiotic coatings
			19.3.1.2 Antimicrobial peptide coatings
			19.3.1.3 Other organic antimicrobial coatings
			19.3.1.4 Inorganic antimicrobial coatings
		19.3.2 Surface nanostructures to prevent bacteria colonization
	19.4 Conclusion
	References
20 Cellular response to metal implants
	20.1 Introduction
	20.2 Metallic implants
		20.2.1 Orthopedic devices
		20.2.2 Cardiac and endovascular implants
		20.2.3 Dental and oral/maxillofacial devices
		20.2.4 Neurological devices
		20.2.5 Gynecological devices
	20.3 Corrosion and metal ion release
	20.4 Cellular response to metal implants
		20.4.1 Inflammatory response
			20.4.1.1 Coagulation, complement activation, and protein adsorption
			20.4.1.2 Danger signals and recognition
			20.4.1.3 Activation of inflammatory cells
		20.4.2 Chronic inflammation
		20.4.3 Adaptive immune response
			20.4.3.1 Sensitization
			20.4.3.2 Effects of metals in adaptive immunity
	20.5 Modulation of host response to implants
	20.6 Conclusion
	References
21 Cellular response to nanobiomaterials
	21.1 Introduction
	21.2 Factors affecting nanobiomaterial–cell interactions
		21.2.1 Chemistry of nanobiomaterials
		21.2.2 Size of nanobiomaterials
		21.2.3 Shape of nanobiomaterials
		21.2.4 Surface topography and stiffness of nanobiomaterials
		21.2.5 Surface charge
		21.2.6 Functional groups of nanobiomaterials
		21.2.7 Hydrophobicity/hydrophilicity of nanobiomaterials
	21.3 Various interactions between nanobiomaterials and cells
		21.3.1 Nanobiomaterial–ECM interactions
		21.3.2 Nanobiomaterial–cell membrane interaction
		21.3.3 Nanobiomaterial–cytoskeleton interactions
		21.3.4 Nanobiomaterial–organelle interactions
		21.3.5 Nanobiomaterial–nuclei interactions
	21.4 Conclusion
	References
Sec 3
22 Central nervous system responses to biomaterials
	22.1 Introduction
		22.1.1 The need for the use of biomaterials in central nervous system
		22.1.2 Classification of biomaterials used in central nervous system
	22.2 Polymers
		22.2.1 Synthetic polymers
			22.2.1.1 Poly(glycolic acid)/poly(lactic acid)/poly(lactic-co-glycolic acid)
			22.2.1.2 Poly(ε-caprolactone)
			22.2.1.3 Poly(ethylene glycol)/poly(ethylene oxide)
			22.2.1.4 Poly(ethylene-co-vinylacetate)
			22.2.1.5 Poly(2-hydroxyethyl methacrylate) and poly(2-hydroxyethyl methacrylate-co-methyl methacrylate)
		22.2.2 Natural polymers
			22.2.2.1 Agarose/alginate
			22.2.2.2 Chitosan/methylcellulose/nitrocellulose
			22.2.2.3 Collagen
			22.2.2.4 Dextran
			22.2.2.5 Fibrin/fibronectin
			22.2.2.6 Hyaluronan/hyaluronic acid
		22.2.3 Conductive polymers
			22.2.3.1 Polypyrrole
			22.2.3.2 Polyaniline
			22.2.3.3 Poly(3,4-ethylenedioxythiopene)
			22.2.3.4 Indium phosphide
			22.2.3.5 Carbon nanomaterials (i.e., graphene, carbon nanotubes)
	22.3 Metals
		22.3.1 Introduction and unspecific toxicities
		22.3.2 Iron (Fe)
		22.3.3 Chromium (Cr)
		22.3.4 Cobalt (Co)
		22.3.5 Molybdenum (Mo)
		22.3.6 Nickel (Ni)
		22.3.7 Titanium (Ti)
		22.3.8 Tungsten (W) and iridium (Ir)
		22.3.9 Platinum (Pt)
		22.3.10 Management of metal induced toxicities
	22.4 Ceramics
		22.4.1 Silicon oxides
		22.4.2 Aluminum oxides
		22.4.3 Titanium oxides
	22.5 Hybrid or composite biomaterials
		22.5.1 Interaction of nanomaterials and nanoparticles with central nervous system
		22.5.2 Carbon nanomaterials
			22.5.2.1 Carbon nanotubes
			22.5.2.2 Fullerenes
			22.5.2.3 Graphene oxide and derived nanomaterials
			22.5.2.4 Nanodiamonds
			22.5.2.5 Carbon nanohorns and carbon nanofibers
			22.5.2.6 Carbon dots
	22.6 Conclusion and future directions
	Conflicts of interest
	References
23 Peripheral nervous system responses to biomaterials
	23.1 Introduction
		23.1.1 Non synthetic nerve guidance conduits
			23.1.1.1 Autografts
			23.1.1.2 Blood vessels
			23.1.1.3 Muscle
	23.2 Allografts
	23.3 Xenografts
	23.4 Natural degradable nerve guidance conduits
		23.4.1 Collagen
		23.4.2 Gelatin
		23.4.3 Fibrin
		23.4.4 Keratin
		23.4.5 Silk
		23.4.6 Chitosan
	23.5 Synthetic nerve guidance conduits
	23.6 Synthetic degradable nerve guidance conduits
	23.7 Polymers
		23.7.1 Poly (e-caprolactone) (PCL)
		23.7.2 Polyurethanes
		23.7.3 Polyglycolic acid
	23.8 Summary
	References
24 Cardiac responses to biomaterials
	24.1 Biomaterials for cardiac applications
	24.2 Foreign body response
	24.3 Biocompatibility testing of biomaterials
		24.3.1 Identification and quantification of the foreign body response—histology
		24.3.2 Identification and quantification of the foreign body response—proteomics
	24.4 Biomaterials
		24.4.1 Mechanical support
			24.4.1.1 Alginate
			24.4.1.2 Decellularized tissue
			24.4.1.3 Hyaluronic acid
			24.4.1.4 Synthetic biomaterials
		24.4.2 Cell delivery
			24.4.2.1 Fibrin
			24.4.2.2 Poly(ethylene glycol)
			24.4.2.3 Cardiac patches—poly(ester urethane)
			24.4.2.4 Cardiac patches—polycaprolactone
			24.4.2.5 Cardiac patches—collagen
			24.4.2.6 Cardiac patches—poly(urethane)
		24.4.3 Growth factor/small molecule delivery
			24.4.3.1 Chitosan
			24.4.3.2 Poly(lactide-co-glycolic acid)
			24.4.3.3 N-isopropylacrylamide
		24.4.4 Prosthetic valves
		24.4.5 Traditional medical devices
			24.4.5.1 Pacemakers and Implantable Cardioverter Defibrillators (ICDs)
			24.4.5.2 Stents
	24.5 State of the art approaches to reduce the foreign body response
		24.5.1 Material properties
		24.5.2 Device design
		24.5.3 Coatings
		24.5.4 Use of angiogenic agents
		24.5.5 Inhibition of TGF-β/use of corticosteroids
		24.5.6 Mechanical actuation
		24.5.7 Monitoring the foreign body response
	24.6 Potential uses of the foreign body response
	24.7 Conclusion
	References
25 Vascular responses to biomaterials
	25.1 Introduction
	25.2 Biomaterials in vascular diseases
		25.2.1 Biocompatibility
		25.2.2 Metals and alloys
		25.2.3 Polymer-based implants
		25.2.4 Biological materials
	25.3 Vascular response to biomaterials
		25.3.1 Biomaterials and clotting
		25.3.2 Biomaterials and acute inflammation
		25.3.3 Restenosis
		25.3.4 Fibrosis
	25.4 Vascular response to biofunctionalization of biomaterials
		25.4.1 Antiproliferative strategies
		25.4.2 Antithrombogenic strategies
		25.4.3 Reendothelialization strategies
		25.4.4 Antiinflammatory and antifibrotic strategies
	25.5 Future perspectives
	References
26 Bone responses to biomaterials
	Abbreviations
	26.1 Introduction
	26.2 Skeletal cell response to biomaterials
		26.2.1 Osteoblasts
		26.2.2 Osteoclasts
		26.2.3 Osteocytes
	26.3 Immune cell response to biomaterials
		26.3.1 Macrophages
		26.3.2 Neutrophils and dendritic cells
		26.3.3 T cells
	26.4 Vascular cell response to biomaterials
	26.5 Conclusion
	References
27 Tendon and muscle responses to biomaterials
	27.1 Introduction
		27.1.1 Composition of tendon and muscle tissues
		27.1.2 Injury and healing of tendon/muscle
	27.2 Management of tendon/muscle injuries and responses
		27.2.1 Suture
		27.2.2 Tissue grafting
	27.3 Regenerative strategies for tendon/muscle injuries
		27.3.1 Hydrogel biomaterials for small tissue repair
		27.3.2 Natural biomaterials for large tissue repairs
			27.3.2.1 Collagen
			27.3.2.2 Silk
		27.3.3 Synthetic materials for large tissue repairs
	27.4 Conclusion
	References
28 Pulmonary system responses to biomaterials
	28.1 Introduction
	28.2 Synthetic biomaterials and their applications in pulmonary administration
		28.2.1 Poly(ethylene terephthalate)
		28.2.2 Poly(tetrafluoroethylene)
		28.2.3 Poly(glycolic acid)
		28.2.4 Polyvinyl alcohol
		28.2.5 Polyethylene glycol
	28.3 Synthetic biomaterials for drug delivery in lungs
	28.4 Uses of synthetic biomaterials in lung tissue engineering
	28.5 Natural biomaterials for pulmonary applications
		28.5.1 Albumin-based biomaterials
		28.5.2 Derivatives from silk
		28.5.3 Chitosan and its derivatives
		28.5.4 Gelatin
		28.5.5 Hyaluronic acid
	28.6 Conclusion
	References
29 Gastrointestinal response to biomaterials
	29.1 Introduction
	29.2 Oral cavity and pharynx
	29.3 Oesophagus
	29.4 Stomach
	29.5 Small intestine
	29.6 Large intestine
	29.7 Conclusion
	References
30 Ocular responses to biomaterials
	30.1 Introduction to biocompatibility in the eye
	30.2 Anatomy and physiology of the eye in relation to biomaterial applications
		30.2.1 The ocular surface
		30.2.2 The anterior segment of the eye
		30.2.3 The posterior segment
	30.3 Ocular response to biomaterials in the anterior chamber
		30.3.1 Ocular response to contact lens and artificial cornea materials
		30.3.2 Ocular response to intraocular lens
		30.3.3 Ocular response to glaucoma shunts and (noncontact lens) drug delivery systems in the anterior eye
	30.4 Ocular response to biomaterials in the posterior segment
	30.5 Conclusion
	References
31 Skin responses to biomaterials
	31.1 Introduction
	31.2 General description of the skin tissue
	31.3 Skin responses to biomaterials
		31.3.1 The inflammatory response induced by biomaterials on skin
		31.3.2 The hypersensitivity responses induced by biomaterials on skin
		31.3.3 The stimuli responses induced by biomaterials on skin
			31.3.3.1 Biomaterial physical properties
			31.3.3.2 Bioactive strategies
			31.3.3.3 Biomaterial mechanical properties and stimulus signal
			31.3.3.4 Metal ions and inorganic compounds
	31.4 The role of scaffolding materials in skin tissue engineering
	31.5 Future perspectives
	References
Index
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