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Table of Contents
                            Biomaterials as Stem Cell Niche (Studies in Mechanobiology, Tissue Engineering and Biomaterials, Volume 2)
	Biomaterials as
Stem Cell Niche
Engineering ECM Complexity into Biomaterials for Directing Cell Fate
	1…Cell--ECM Interactions
		1.1 ECM Composition and Signaling
		1.2 ECM Regulation
			1.2.1 Proteolytic Processing of the ECM
			1.2.2 Mechanochemical Translation of Cell-binding ECM Domains
	2…ECM and the Stem Cell Niche
		2.1 Integrins: A Sign of ‘‘Stemness’’
		2.2 Neural Stem Cells and Integrin/ECM Alterations
			2.2.1 Integrin and ECM Profile During Neural Development
			2.2.2 ECM and Integrin Profile in Adult Neural Stem Cell Niche
			2.2.3 Functional Role of ECM/Integrin Interactions
	3…Current Biomaterials Approaches
		3.1 Biomimetic Approaches
		3.2 Engineering Protein Variants
		3.3 Future Directions for Biomaterials as Stem Cell Niches
Functional Biomaterials for Controlling Stem Cell Differentiation
		1.1 Emergence of Stem Cell Engineering  in Regenerative Medicine
		1.2 Stem Cell Sources
	2…Stem Cell Expansion and Differentiation Using Biomaterials
		2.1 Roles of ECM in Stem Cell Differentiation
		2.2 Mimicking ECM with Synthetic Biomaterials
			2.2.1 Mimicking the Biophysical and Biochemical Properties of ECM
				Functionalization of Synthetic Substrates with ECM Derived Ligands
			2.2.2 Effects of the Cell--Matrix Interface
				Surface Chemistry and Interfacial Energy
			2.2.3 Mineralization of Matrix Materials
				Mineralization of Polymeric Matrices
				Effect of Mineralization on Cell Adhesion, Proliferation and Differentiation
			2.2.4 Mechanical Properties
		2.3 Biomaterial Based Delivery of Soluble Factors  for 3D Cell Culture
			2.3.1 Incorporation of Bioactive Agents into Matrix Materials
			2.3.2 Effects of Controlled Delivery of Bioactive Agents  on Stem Cell Differentiation
				Delivery of Bioactive Agents to Embryonic Stem Cells
				Tissue Specific Differentiation of Stem Cells Using  Delivery of Bioactive Agents
		2.4 In Vivo Applications
		2.5 Future Perspectives
Integration of Biomaterials into  3D Stem Cell Microenvironments
		1.1 Culture in Two or Three Dimensions
		1.2 Strategies for Biomaterial Control of the 3D Microenvironment
	4…Microcarriers and Microparticles
		4.1 Microcarriers
		4.2 Microparticles
	5…Summary and Conclusions
Stem Cell Interaction with Topography
		1.1 Extracellular Topography
		1.2 Nanotopography
	2…Nanofabrication Techniques
	3…Stem Cells Reception to Topography
		3.1 Embryonic Stem Cells
		3.2 Neural Progenitor Cells/Neural Stem Cells
		3.3 Mesenchymal Stem Cells
	4…Making Sense of Physical Cues in the Extracellular Matrix: Mechanotransduction
		4.1 Introduction to the ECM
		4.2 Mechanotransduction: A Direct Connection?
		4.3 Connecting with the ECM: Cell--Matrix Interactions
		4.4 Integrins and Focal Adhesions: Inside Out and Outside In
		4.5 Cytoskeleton: Force Transmission
			4.5.1 Cell Exerting Forces on the Underlying Substrate
		4.6 Filopodia: Probing the ECM
		4.7 Nucleus: Gene Regulation
The Nanofiber Matrix as an Artificial Stem Cell Niche
	1…The Stem Cell Niche
	2…Nanoscale Topography in the Extracellular Matrix
	3…Methods to Generate Nanofibrous Matrices
		3.1 Electrospinning
		3.2 Self-assembly
		3.3 Solution Phase Separation
		3.4 Comparison of Nanofiber Generation Methods
	4…Nanofibrous Matrices for Stem Cell Expansion
		4.1 Nanofiber-mediated Expansion of Human Hematopoietic  Stem Cells (HSCs)
		4.2 Nanofiber-mediated Expansion of Neural Stem Cells (NSCs)
		4.3 Nanofiber-mediated Expansion of Embryonic Stem  Cells (ESCs)
		4.4 Nanofiber-mediated Expansion of Mesenchymal  Stem Cells (MSCs)
	5…Nanofiber Matrices for Differentiation of Stem Cells
		5.1 Nanofiber-mediated Stem Cell Differentiation into  Neuronal Lineages
		5.2 Nanofiber-mediated Stem Cell Differentiation into  Chondrogenic and Osteogenic Lineages
		5.3 Nanofiber-mediated Stem Cell Differentiation into  Myogenic Lineage
	6…Nanofibrous Matrices for Stem Cell Delivery
Micropatterned Hydrogels  for Stem Cell Culture
	1…Introduction: Application of Biomaterial Technologies  to Stem Cell Research
	2…Stem Cells
		2.1 MSC General Characteristics
		2.2 MSC Differentiation and Plasticity
		3.1 Natural Versus Synthetic Polymers
		3.2 Gelation Mechanisms
			3.2.1 Radical Chain Polymerization
			3.2.2 Chemical Cross-linking
		3.3 Functionalization of Hydrogels
			3.3.1 Biodegradable Hydrogels
			3.3.2 Biomimetic hydrogels
		4.1 Microfabrication Technology
		4.2 Applications in Hydrogel Patterning
			4.2.1 Photolithography
			4.2.2 Laser-scanning lithography
			4.2.3 Stop-flow Lithography
			4.2.4 Optofluidic Maskless Lithography
			4.2.5 Photodegradation
			4.2.6 Micromolding
			4.2.7 Two-dimensional Templating
	5…Micropatterning Hydrogels with Embedded Cells
		5.1 Culture of One Cell Type
			5.1.1 Cell Viability
			5.1.2 Cell Migration (and Morphology)
			5.1.3 Cell Differentiation
		5.2 Culture of Multiple Cell Types
			5.2.1 Microfluidics
			5.2.2 Bioreactors
			5.2.3 Micromolding
			5.2.4 Stop-flow Lithography
	6…Future Outlook
Microengineering Approach for Directing Embryonic Stem Cell Differentiation
	2…Control of the Cellular Microenvironment
		2.1 Cell--cell Contacts
		2.2 Cell--soluble Factor Interactions
		2.3 Cell--extracellular Matrix Interactions
	3…Microengineering the Environment
		3.1 Microfluidic Platforms for Controlling Cell--soluble Factor Interactions
		3.2 Controlled Microbioreactors
		3.3 Surface Micropatterning for Controlling Cell--cell Contacts
		3.4 High-throughput Microarrays for Screening Microenvironments
		3.5 Three Dimensional Scaffolds for Culturing ESCs
		3.6 Tissue Engineering Using Assembly of Microengineered Building Blocks
Biomaterials as Stem Cell Niche: Cardiovascular Stem Cells
	2…Adult Cardiovascular Stem Cells and Their Niches
		2.1 Cardiac Stem Cells
		2.2 Endothelial Progenitor Cells
		2.3 Mural Cell Progenitors/Mesenchymal Stem Cells
		2.4 Adult Cardiovascular Stem Cell Niches
	3…Biomaterials as Stem Cell Niches for 3D Cell Culture
		3.1 3D Cell Culture Systems for Pluripotent Stem Cells
		3.2 3D Cell Culture Systems for Adult Stem Cells
	4…Biomaterials as Stem Cell Niches for Cardiac Cell Therapy
		4.1 Cardiac Cell Therapy
		4.2 Biomaterial Scaffolds for Cardiac Cell Therapy
The Integrated Role of Biomaterials  and Stem Cells in Vascular Regeneration
	2…Stem Cells for Vascular Regeneration
		2.1 Vascular Development of ECs and SMCs from Pluripotent Stem Cells
		2.2 Stem-cell-derived Vascular Cells
			2.2.1 Stem-cell-derived ECs
				Endothelial Progenitor Cells
				ECs Derived from ESC and iPSC Populations
			2.2.2 Stem-cell-derived SMCs
	3…Biomimetic Scaffolds for Vascular Regeneration
		3.1 General Requirements for Biomimetic Scaffolds
		3.2 Polymeric Biomimetic Scaffolds
		3.3 Scaffold Types
			3.3.1 Hydrogels
			3.3.2 Electrospun Fibers
			3.3.3 Other Scaffolds
		3.4 Vascular Engineering Scaffold Properties
			3.4.1 Degradation Properties
			3.4.2 Substrate Topography
			3.4.3 Mechanical Stimulation
	4…Inclusion of Vascular Stem and Somatic Cells into Biomaterials
		4.1 Biomaterials to Engineer Blood Vessels
		4.2 Biomaterials to Deliver Cells to Host Vasculature
		4.3 Biomaterials to Induce Differentiation
	5…Future Perspectives
Synthetic Niches for Stem Cell Differentiation into T cells
	2…The T Cell Niche
		2.1 T Cell Receptor Gene Rearrangement
		2.2 T Cell Microenvironment
	3…T Cell Differentiation Through Co-culture
	4…T Cell Differentiation Through Immobilization  of Notch Ligands
		4.1 T Cell Differentiation Through Plate Immobilization
		4.2 T Cell Differentiation Through Notch--Ligand Presenting Microbeads
	5…Generation of Antigen-specific T Cells from Stem Cells
		5.1 Retroviral Transduction of T Cell Receptors
		5.2 T Cell Differentiation in a Three-dimensional Matrix
Understanding Hypoxic Environments: Biomaterials Approaches to Neural Stabilization and Regeneration after Ischemia
	1…Ischemic Brain Damage in Adult and Neonatal Humans
	2…Response of NSPCs to Ischemic Brain Damage
	3…NSPC Implants to Treat Ischemic Brain Damage
	4…NSPC Isolation and Culture: State-of-the-Art
	5…Biomaterials Use in NSPC Applications: State-of-the-Art
	6…Current Challenges in Biomaterials for NSPC Applications
	7…Potential of Biomaterials for Reverse-engineering NSPC Microenvironments
		7.1 Neurosphere Culture
		7.2 The Stem Cell Niche
		7.3 ‘‘Physiological Hypoxia’’ and Hypoxic/Ischemic Injury
Biomaterial Applications in the Adult Skeletal Muscle Satellite Cell Niche: Deliberate Control of Muscle Stem Cells and Muscle Regeneration  in the Aged Niche
	2…Skeletal Muscle is Regenerated and Maintained  by Muscle Stem Cells
		2.1 Delta/Notch Signaling Leads to Activation  and Proliferation of Satellite Cells
		2.2 Wnt Signaling Cues Myogenic Progenitor Cells to Differentiate
	3…The Aged Skeletal Muscle Niche Impairs Normal 	Regeneration: TGF- beta 1 Signaling Maintains Satellite 	Cell Quiescence and Leads to Scar Tissue Formation
	4…Toolbox to Combat TGF- beta 1-induced Aging 	of Satellite Cell Niche
	5…Biomaterials to the Rescue: Proposed Strategies for Adult Skeletal Muscle Regeneration
		5.1 Engineering an In Vitro Niche for Robust  Skeletal Muscle Regeneration
			5.1.1 Alignment of In Vitro Skeletal Muscle Fibers
			5.1.2 Effects of Synthetic Niche Stiffness on Skeletal Muscle Regeneration
			5.1.3 Electrical Stimulation of Tissue-engineered Skeletal Muscle
			5.1.4 Vascularization of Tissue-engineered Skeletal Muscle
			5.1.5 Natural Skeletal Muscle Niches: Mimicking the In Vivo Environment
		5.2 Biomaterial Strategies to Combat Aging  of the Muscle Stem Cell Niche
			5.2.1 Gene and Drug Delivery Methods to Promote  Skeletal Muscle Regeneration
			5.2.2 Novel Targeting Strategies for TGF- beta 1 Inhibition
				A biomaterial platform for regulating TGF- beta 1 levels to ‘young’ levels in the aged niche
		5.3 Satellite Cells and Muscle Stem Cells: Biomaterials 	to Help Determine Who is Who
		5.4 Use of Biomaterials in Tissue Engineering Applications
Author Index
Document Text Contents
Page 2

Studies in Mechanobiology, Tissue Engineering
and Biomaterials

Volume 2

Series Editor
Dr. Amit Gefen
Department of Biomedical Engineering
The Iby and Aladar Fleischman Faculty of Engineering
Tel Aviv University
69978 Ramat Aviv
e-mail: [email protected]

Further volumes of this series can be found on our homepage:

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Page 311

Author Index

Ali Khademhosseini, 153
Ameya Phadke, 19
Amir Foudeh, 153
Andres Bratt Leal, 45
Ankur Singh, 225
Ashley Carson Brown, 1

Behnam Zamanian, 153
Benjamin K. K. Teo, 61

Cheong Hoon Kwon, 153
Chien Wen Chang, 19

Elizabeth M. Powell, 247
Eric Jabart, 275
Evelyn K. F. Yim, 61

Ge Zhang, 173
Gregory Christopherson, 89
Guoming Sun, 195

Hai Quan Mao, 89
Hang Lu, 119
Hojae Bae, 153

Irina Conboy, 275

Jason W. Nichol, 153
Jennie B. Leach, 247
Johnna S. Temenoff, 119

Korey Kam, 89
Krishnendu Roy, 225

Laura J. Suggs, 173

Richard Carpenedo, 45

Sarah E. Stabenfeldt, 1
Sharon Gerecht, 195
Sharon K. Hamilton, 119
Shawn H. Lim, 89
Shuming Zhang, 89
Shyni Varghese, 19
Soneela Ankam, 61
Sravanti Kusuma, 195
Stephen Fischer, 89

Thomas H. Barker, 1
Todd McDevitt, 45


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