Biomaterials in Tissue Engineering and Regenerative Medicine: From Basic Concepts to State of the Art Approaches

Contents
About the Editors
List of Abbreviations
Part I: Fundamentals of Biomaterials
	1: Biomaterials, Tissue Engineering, and Regenerative Medicine: A Brief Outline
		1.1 Introduction
			1.1.1 Biomaterials
			1.1.2 Tissue Engineering
			1.1.3 Regenerative Medicine
		References
	2: Metallic Biomaterials in Tissue Engineering: Retrospect and Prospects
		2.1 Introduction
			2.1.1 Traditional Metallic Biomaterials
			2.1.2 Advanced and Revolutionizing Metallic Biomaterials
			2.1.3 Metallic Biomaterials and Biocompatibility
		2.2 Properties of Metallic Biomaterials
			2.2.1 Phase Transformation and Elastic Moduli
			2.2.2 Porosity
			2.2.3 Corrosion Resistance
			2.2.4 Anti-Bacterial Properties
			2.2.5 Bioactivation of Metallic Biomaterials
			2.2.6 Biodegradation
			2.2.7 MRI Compatibility
			2.2.8 Radiopacity
		2.3 Permanent Metallic Biomaterials
			2.3.1 Stainless Steel
			2.3.2 Co-Based Biomaterials
			2.3.3 Ti-Based Biomaterials
			2.3.4 Tantalum and Its Alloys
			2.3.5 Zirconium Alloys
		2.4 Biodegradable Metallic Biomaterials
			2.4.1 Mg-Based Biomaterials
			2.4.2 Zinc-Based Biomaterials
			2.4.3 Iron-Based Biomaterials
		2.5 Advanced Metallic Biomaterials
			2.5.1 Bulk Metallic Glasses
			2.5.2 Shape Memory Alloys
		2.6 Tissue Engineering Applications of Metallic Biomaterials
			2.6.1 Bone Tissue Engineering
			2.6.2 Cartilage Tissue Engineering
			2.6.3 Cardiovascular Tissue Engineering
			2.6.4 Dental Tissue Engineering
		2.7 Future Prospects of Metallic Biomaterials in Tissue Engineering
		References
	3: Bioceramics in Tissue Engineering: Retrospect and Prospects
		3.1 Introduction
		3.2 Background Perspective
		3.3 Bioactivity of Calcium Phosphate
			3.3.1 Calcium Phosphates: Variants and Effects
			3.3.2 CaPO4 Bioceramics in Tissue Engineering
			3.3.3 Clinical Vignettes
		3.4 Summary and Outlook
		References
	4: Polymeric Biomaterials in Tissue Engineering: Retrospect and Prospects
		4.1 Introduction
		4.2 Extracellular Matrix-the Framework Enabling Tissue Growth
		4.3 Polymeric Materials as Ideal Scaffold
		4.4 Natural and Synthetic Polymers as Scaffolds
		4.5 Natural Biodegradable Polymers
			4.5.1 Collagen
			4.5.2 Gelatin
			4.5.3 Chitosan
			4.5.4 Alginate
			4.5.5 Fibrin
			4.5.6 Hyaluronic Acid
			4.5.7 Silk
		4.6 Synthetic Biodegradable Polymers
			4.6.1 Poly Lactic Acid (PLA)
			4.6.2 Poly (glycolic acid) (PGA)
			4.6.3 Poly (lactic-co-glycolic acid) (PLGA)
			4.6.4 Poly(caprolactone) (PCL)
			4.6.5 Poly Vinyl Alcohol (PVA)
			4.6.6 Poly-β-hydroxybutyrate
			4.6.7 Polyethylene Glycol-Based Polymers
		4.7 Polymer Scaffold Fabrication Techniques
			4.7.1 Conventional (Traditional) Manufacturing Techniques
			4.7.2 Nano Fabrication-Based Techniques
			4.7.3 Additive Manufacturing-Based Techniques
		4.8 Conclusion and Perspectives
		References
	5: Composite Biomaterials in Tissue Engineering: Retrospective and Prospects
		5.1 Introduction
		5.2 Bio-Composite Components: Classes and Desirable Properties
		5.3 Strategies of Bio-Composite Development
			5.3.1 Conventional Blending and Mixing Technique
			5.3.2 Advanced Bio-Fabrication Methods
				5.3.2.1 Co-electrospinning
				5.3.2.2 Bioprinting
				5.3.2.3 Reinforcement Methods
			5.3.3 Nano-Particle Reinforced Bio-Composites
			5.3.4 Surface Modifications
			5.3.5 Surface Effects and Characterization
		5.4 Retrospectives of Composite Biomaterials in Tissue Engineering
			5.4.1 Composite Biomaterials for Hard Tissue Regeneration
				5.4.1.1 Bone Tissue Regeneration
				5.4.1.2 Dentistry
			5.4.2 Composite Biomaterials in Soft Tissue Engineering
				5.4.2.1 Vascular Grafting
				5.4.2.2 Cardiac Tissue Engineering
				5.4.2.3 Contact Lens and Cornea
				5.4.2.4 Neural Tissue Engineering
		5.5 Bottlenecks of Composite Biomaterial Applications
		5.6 Prospects of Composite Biomaterials
		5.7 Conclusion
		References
Part II: Trends in Biomaterials
	6: Trends in Bio-Derived Biomaterials in Tissue Engineering
		6.1 Introduction
		6.2 Concept of Bio-Derived Biomaterials and their Applications in Tissue Engineering
		6.3 Decellularized Extracellular Matrix (DECM) as Biomaterials
			6.3.1 ECM and Decellularization
			6.3.2 Methods of Decellularization
			6.3.3 Regenerative Properties of DECM
			6.3.4 Decellularized Material Systems: Applications in Tissue Engineering
		6.4 Naturally Derived Biomaterials
			6.4.1 Proteins Based Bio-Derived Biomaterials
				6.4.1.1 Collagen
				6.4.1.2 Gelatin
				6.4.1.3 Fibrin
				6.4.1.4 Silk
				6.4.1.5 Keratin
			6.4.2 Polysaccharides Based Bio-Derived Biomaterials
				6.4.2.1 Glycosaminoglycans
				6.4.2.2 Alginates
				6.4.2.3 Agarose
				6.4.2.4 Carrageenan
				6.4.2.5 Chitosan
			6.4.3 Other Bio-Derived Biomaterials
		6.5 Microbial Derived Biopolymers
			6.5.1 Types of Bacterial Polymers
			6.5.2 Biosynthesis and Purification of Bacterial-Derived Polymers
				6.5.2.1 Polyamides
				6.5.2.2 Polyesters
				6.5.2.3 Polysaccharides
			6.5.3 Microbial Derived Biopolymers for Tissue Engineering
				6.5.3.1 Poly-γ-Glutamic Acid (γ-PGA)
				6.5.3.2 Polyhydroxyalkanoates (PHAs)
				6.5.3.3 Polysaccharides
		6.6 Conclusion and Future Directions
		References
	7: Trends in Functional Biomaterials in Tissue Engineering and Regenerative Medicine
		7.1 Functionalized Biomaterials
		7.2 Surface Functionalization Methods
			7.2.1 Surface Roughening and Patterning
			7.2.2 Surface Films and Coatings
				7.2.2.1 Physical Methods
					7.2.2.1.1 Physical Adsorption of Active Biomolecules
					7.2.2.1.2 Langmuir-Blodgett Method
					7.2.2.1.3 Physical Vapor Deposition
						Evaporation
						Deposition by Sputtering
						Plasma immersion ion implantation and deposition (PIIIandD)
					7.2.2.1.4 Electrophoretic Deposition
					7.2.2.1.5 Spraying Techniques
				7.2.2.2 Chemical Methods
					7.2.2.2.1 Adsorption Via Covalent Bonding
					7.2.2.2.2 Alkali Acid Hydrolysis
					7.2.2.2.3 Chemical Vapor Deposition
						Plasma-Enhanced Chemical Vapor Deposition
						Plasma Polymerization
						Atomic Layer Deposition
					7.2.2.2.4 Sol-Gel Technique
					7.2.2.2.5 Layer-by-Layer (LbL) Deposition
				7.2.2.3 Radiation Methods
			7.2.3 Surface Modification by Addition of Signaling Biomolecules
		7.3 Functionalized Scaffolds Towards Organ Development
			7.3.1 Cardiac Tissue
			7.3.2 Liver
			7.3.3 Lung
			7.3.4 Bone
			7.3.5 Dental Implants
		7.4 Conclusion and Future Perspectives
		References
	8: Trends in Bioactive Biomaterials in Tissue Engineering and Regenerative Medicine
		8.1 Tissue Engineering
		8.2 Bioactive Scaffolds
		8.3 Incorporation of Bioactive Components
			8.3.1 Bioactivity by Incorporation of Adhesion Sites
			8.3.2 Nanopatterning
			8.3.3 Bioactivity by Incorporation of Growth Factors
			8.3.4 Bioactivity by Physiochemical Interactions
			8.3.5 Bioactivity by Material Transformation
		8.4 Bioactive Inorganic Biomaterials for Tissue Engineering
		8.5 Injectable Biomaterials
		8.6 Bioactive Scaffolds: Tissue Engineering Applications
			8.6.1 Neural Tissue Engineering
			8.6.2 Vascular Tissue Engineering
			8.6.3 Cardiac Tissue Engineering
		8.7 Biomaterial Based Stem Cell Therapy in Regenerative Medicine
		8.8 Scaffolds for Biomolecule Delivery
			8.8.1 Properties
		8.9 Biomolecule Delivery Systems
			8.9.1 Hydrogel-Based Systems
			8.9.2 Nanoparticle Based Systems
			8.9.3 Liposomes
			8.9.4 Micelles
			8.9.5 Microparticles
			8.9.6 Dendrimers and Elastomers
			8.9.7 Microchips
		8.10 Scaffold Based Biomolecule Delivery
			8.10.1 Delivery of Therapeutic Drugs
			8.10.2 Delivery of Therapeutic Cells
			8.10.3 Scaffold Based Peptide Delivery
			8.10.4 Scaffolds for Gene Delivery
		8.11 Biomolecule Loaded Scaffolds in Tissue Engineering: Applications
			8.11.1 Bone Tissue Engineering
			8.11.2 Skin Tissue Engineering
			8.11.3 Cartilage Tissue Engineering
		8.12 Future Perspectives
		References
	9: Trends in Stimuli Responsive Biomaterials in Tissue Engineering
		9.1 Introduction
		9.2 Stimuli Responsive Biomaterials in Tissue Engineering
			9.2.1 Electroactive Biomaterials
				9.2.1.1 Conducting Polymers
					9.2.1.1.1 Conducting Polymers in Tissue Engineering
				9.2.1.2 Piezoelectric Material
					9.2.1.2.1 Piezoelectric Materials in Tissue Engineering
				9.2.1.3 Electrets
					9.2.1.3.1 Electrets in Tissue Engineering
				9.2.1.4 Photovoltaics
					9.2.1.4.1 Photovoltaic Materials in Tissue Engineering
				9.2.1.5 Carbon Based Nanomaterials
					9.2.1.5.1 Carbon Based Nanomaterials in Tissue Engineering
			9.2.2 Magnetoresponsive Biomaterials
			9.2.3 Thermoresponsive Biomaterials
			9.2.4 Photoresponsive Biomaterials
			9.2.5 Chemical Stimuli Responsive Biomaterials
			9.2.6 Biological Stimuli Responsive Biomaterials
		9.3 Conclusions and Future Outlook
		References
Part III: Applications of Biomaterials
	10: Biomaterials for Hard Tissue Engineering: Concepts, Methods, and Applications
		10.1 Introduction
		10.2 Biomaterials for Bone Tissue Engineering
			10.2.1 Polymers and Hydrogels
			10.2.2 Hybrid Scaffolds in Bone Tissue Engineering
		10.3 Applications of Tissue Engineering in Dentistry
			10.3.1 Tooth Regeneration
			10.3.2 Bone Regeneration in Dental Application
			10.3.3 Enamel Regeneration
			10.3.4 Dentin and Dental Pulp Regeneration
		10.4 Biomaterials Used in Dentistry
		10.5 Dental Stem Cells in Hard and Soft Tissue Engineering in Dentistry
		10.6 Advanced Tissue Engineering Strategies
			10.6.1 3D Printing in Hard Tissue Engineering
			10.6.2 3D Bioprinting in Hard Tissue Engineering
		10.7 Shape Memory Polymers in Hard Tissue Engineering
		10.8 Tissue Engineering Challenges in Dentistry
		10.9 Current Clinical Trials in Dentistry
		10.10 Concluding Remarks and Outlook
		References
	11: Biomaterials for Soft Tissue Engineering: Concepts, Methods, and Applications
		11.1 Introduction
		11.2 The Properties of Scaffolds for Soft Tissue Engineering
			11.2.1 Biological Properties
			11.2.2 Physicochemical Properties
				11.2.2.1 Cytotoxicity
				11.2.2.2 Fabrication Techniques
				11.2.2.3 Surface Properties of TE Scaffolds
			11.2.3 Mechanical Properties
		11.3 Application of TE Scaffolds in Soft Tissue Engineering
			11.3.1 Vascular Tissue Engineering
				11.3.1.1 Structure of Blood Vessels
				11.3.1.2 Need for Vascular Tissue Engineering
				11.3.1.3 Tissue Engineered Vascular Graft
					11.3.1.3.1 Electrospun Scaffold-Guided Vascular Grafts
			11.3.2 Skin Regeneration
				11.3.2.1 Structure of Skin
				11.3.2.2 Need for Skin Tissue Engineering
				11.3.2.3 Tissue Engineered Skin Grafts
					11.3.2.3.1 Injectable Hydrogels for Skin Tissue Engineering
					11.3.2.3.2 Nanofibrous Scaffolds for Skin Tissue Engineering
			11.3.3 Cartilage Tissue Engineering
				11.3.3.1 Structure of Cartilage
				11.3.3.2 Need for Cartilage Regeneration
				11.3.3.3 Tissue Engineered Cartilage
					11.3.3.3.1 Injectable Hydrogels
					11.3.3.3.2 Nanofibrous Scaffolds
			11.3.4 Intervertebral Disc (IVD)
				11.3.4.1 The Structure of the IVD
				11.3.4.2 Need for the Disc Repair
				11.3.4.3 Tissue Engineered Disc
					11.3.4.3.1 Nanofibrous/Hydrogel Scaffolds for Disc Repair
			11.3.5 Tendon Repair and Regeneration
				11.3.5.1 Structure of Tendon
				11.3.5.2 Need for Tendon Repair
				11.3.5.3 Tissue Engineered Tendon
					11.3.5.3.1 Injectable Hydrogels Systems
					11.3.5.3.2 Implantable Fibers System
			11.3.6 Skeletal Muscle Tissue Engineering
				11.3.6.1 Structure of Skeletal Muscle
				11.3.6.2 Need for Skeletal Repair/Regeneration
				11.3.6.3 Tissue Engineered Skeletal Muscle
					11.3.6.3.1 Injectable Hydrogels for Skeletal Muscle Regeneration
					11.3.6.3.2 Nanofibrous Scaffolds for Skeletal Muscle Regeneration
		11.4 Future Perspective
		11.5 Conclusion
		References
	12: Biomaterials for Specialized Tissue Engineering: Concepts, Methods, and Applications
		12.1 Introduction
		12.2 Biomaterials for Nerve Tissue Engineering
			12.2.1 Nerve Guidance Conduits
				12.2.1.1 Biological Conduits
				12.2.1.2 Synthetic NGCs
				12.2.1.3 Surface Micropatterning of NGCs
				12.2.1.4 NGC Luminal Fillers
				12.2.1.5 Stem Cell-Based NGCs
				12.2.1.6 NGCs with Sustained Release of Growth Factors
				12.2.1.7 Conductive NGCs
				12.2.1.8 Carbon-Based Nanomaterial-Interfaced NGCs
				12.2.1.9 Ultrasound Treatment Following NGC Implantation
				12.2.1.10 Porcine Small Intestine Submucosa Made NGCs
			12.2.2 Scaffolds for Nerve Tissue Engineering
				12.2.2.1 Synthetic Scaffolds
				12.2.2.2 Piezoelectric Scaffolds
				12.2.2.3 Electroconductive Scaffolds
				12.2.2.4 Conductive Hydrogels
				12.2.2.5 Magnetic Scaffolds and Nanoparticles
				12.2.2.6 ECM-Derived Scaffolds
		12.3 Biomaterials for Pancreatic Tissue Engineering
			12.3.1 Biomaterials in Restoring Pancreatic Function
				12.3.1.1 Biological Polymer Scaffolds
				12.3.1.2 Synthetic Polymer Scaffolds
				12.3.1.3 Silk Fibroin
			12.3.2 Decellularized Pancreas as Native ECM Scaffold
			12.3.3 Surface Engineering of the Pancreatic Islets
		12.4 Future Perspectives
		References
	13: Biomaterials and Stem Cells in Tissue Engineering and Regenerative Medicine: Concepts, Methods, and Applications
		13.1 Introduction
			13.1.1 Biomaterials
			13.1.2 Stem Cells
			13.1.3 Concept of Stem Cell
			13.1.4 Different Types of Stem Cells
			13.1.5 Tissue Engineering and Regenerative Medicine
		13.2 Biomaterials and Stem Cells in TE and RM
		13.3 Applications of Biomaterials and Stem Cells in TE and RM
			13.3.1 Stem Cells and Biomaterials in Bone Tissue Engineering
			13.3.2 Stem Cells and Biomaterials in Cardiovascular TE and RM
			13.3.3 Stem Cells and Biomaterials in Pancreatic Tissue Engineering
			13.3.4 Stem Cells and Biomaterials in Nerve TE
			13.3.5 3D Bioprinting and Stem Cells in TE
		13.4 Conclusion
		13.5 Future Prospects
		References
Part IV: Advances in Biomaterials
14: Biomaterials in Tissue Engineering and Regenerative Medicine: In Vitro Disease Models and Advances in Gene-Based Therapies
	14.1 Introduction
	14.2 In Vitro Disease Models
		14.2.1 Different In Vitro Disease Models Used in TE andRM
			14.2.1.1 Primary Skin Fibroblasts as a Model of Parkinson´s Disease
				14.2.1.1.1 Advantage of Skin Fibroblasts as an In Vitro Model of PD
		14.2.2 In Vitro Model Study of Fibroblast Activation Using Hydrogel Scaffolds
		14.2.3 Induced Pluripotent Stem Cells as In Vitro Disease Models
		14.2.4 Human Mesenchymal Stem Cells as In Vitro Disease Models
		14.2.5 Progress in In Vitro Disease Models
	14.3 Gene Therapy and Its Applications
		14.3.1 Applications
		14.3.2 GT in Tissue Engineering and Regenerative Medicine
			14.3.2.1 Heart Diseases
			14.3.2.2 Lungs Diseases
			14.3.2.3 Liver Diseases
			14.3.2.4 Kidney Diseases
			14.3.2.5 Brain Diseases
	14.4 Advances in Gene-Based Therapies and Its Applications in TE and RM
		14.4.1 Adenovirus as Gene Therapy Vectors
			14.4.1.1 Adenovirus Based Therapy Using Antisense/Small Interfering RNA
			14.4.1.2 Cancer Vaccines Based on Adenoviruses
			14.4.1.3 Gene Therapy: Applications with Haematopoietic Stem Cells
			14.4.1.4 Gene Therapy and CAR-T
			14.4.1.5 Gene Therapy in the Treatment of Adult-Onset Glaucoma
	14.5 Biomaterials in TE Based on GT
	14.6 Challenges and Future Prospects
	References
15: Nanobiomaterials in Tissue Engineering and Regenerative Medicine: Current Landscape and Future Prospects
	15.1 Introduction
		15.1.1 Bio and Immuno Compatibility of Nanobiomaterials
	15.2 Nanobiomaterials in Tissue Engineering and Regenerative Medicine
		15.2.1 Neural Tissue Engineering
			15.2.1.1 Types of Nano-Based Scaffolds Used in NTE
	15.3 Nanobiomaterials and Bone Tissue Engineering/Regeneration
		15.3.1 Nanobiomaterials Used in BTE
		15.3.2 Nanohydroxyapatite (nHA)
			15.3.2.1 nHA in Stem Cell Differentiation During Bone TE
			15.3.2.2 nHA in Skeletal Defects Restoration
			15.3.2.3 nHA in Internal Fixation
			15.3.2.4 nHA in Spinal Fusion
		15.3.3 Nanostructured Calcium Phosphate (CaP)
		15.3.4 Graphene Nanobiomaterials
		15.3.5 Titanium Nanobiomaterials
		15.3.6 Silica Nanobiomaterials
		15.3.7 Bioactive Glass Nanobiomaterials
	15.4 Nanobiomaterials in Tissue Engineering of Bone Associated Tissues
		15.4.1 Craniofacial and Dental Tissue Engineering
			15.4.1.1 nHA in Dental Restoration
			15.4.1.2 Nano-Titanium in Dental Regeneration
			15.4.1.3 Synthetic Silicate Nanoparticles in Dentistry
			15.4.1.4 Graphene in Craniofacial Bone Tissue Engineering
		15.4.2 Cartilage Tissue Regeneration (Temporomandibular Joint)
	15.5 Nanobiomaterials in Corneal Tissue Engineering
		15.5.1 Natural Polymers
		15.5.2 Synthetic Polymers
		15.5.3 Nanobiomaterials in Corneal Epithelial Tissue Engineering
		15.5.4 Nanobiomaterials in Corneal Endothelial Tissue Engineering
		15.5.5 Nanobiomaterials in Corneal Stroma Tissue Engineering
		15.5.6 Cell Sheet Engineering in Corneal Tissue Engineering
	15.6 Limitations and Future Prospects
	References
16: Intelligent Biomaterials for Tissue Engineering and Biomedical Applications: Current Landscape and Future Prospects
	16.1 Introduction
	16.2 Historical Account of Intelligent Biomaterials
	16.3 Shape Changing Materials
	16.4 Thermoresponsive Biomaterials
	16.5 Photoresponsive Biomaterials
	16.6 pH-Responsive Biomaterials
	16.7 Magneto-Responsive Biomaterials
	16.8 Electro-Responsive Biomaterials
	16.9 Bio-Responsive Biomaterials
		16.9.1 Enzyme-Responsive Biomaterials
		16.9.2 Stress-Responsive Biomaterials
		16.9.3 Immuno-Responsive Biomaterials
	16.10 Other Stimuli-Responsive Biomaterials
	16.11 Summary and Future Prospects
	References
17: 3D Bioprinting in Tissue Engineering and Regenerative Medicine: Current Landscape and Future Prospects
	17.1 Introduction
	17.2 Background to 3D Bioprinting
		17.2.1 Historical Account of 3D Printing/Bioprinting
		17.2.2 Set Up and Work Flow of 3D Printing/Bioprinting
		17.2.3 Types and Principles of 3D Bioprinting
			17.2.3.1 Extrusion Bioprinting
			17.2.3.2 Inkjet Bioprinting
			17.2.3.3 Laser Assisted Bioprinting
	17.3 Bioinks in 3D Bioprinting
	17.4 Approaches in Bioprinting
		17.4.1 Single Component Bioink Based Approaches
		17.4.2 Multi-component Bioink Based Approaches
		17.4.3 Approaches Involving Bioinks with Sacrificial Elements
		17.4.4 Combinatorial Approaches in 3D Printing/Bioprinting
	17.5 Summary and Future Prospects
	References
Index