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Bio-Instructive Scaffolds for Musculoskeletal Tissue Engineering and Regenerative Medicine

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Contents

Contributors

Part I: Introduction

Chapter 1: Bio-Instructive Cues in Scaffolds for Musculoskeletal Tissue Engineering and Regenerative Medicine

1.1 Introduction

1.1.1 Role of the Cellular Microenvironment

1.1.2 Current Challenges

1.2 The Cellular Microenvironment: Key Aspects

1.2.1 What is the Microenvironment?

1.2.2 Components of the Microenvironment

1.2.2.1 Cells

1.2.2.2 Soluble Signaling Molecules

1.2.2.3 Extracellular Matrix

Biochemical Properties of ECM: Molecular Structure and Composition

Biochemical Properties of ECM: Cell–ECM Interactions

Physical Properties of ECM

1.3 Recapitulation of Cellular Microenvironments With Bioinstructive Scaffolds

1.3.1 Natural Versus Synthetic Biomaterials

1.3.2 Engineering Biochemical Properties

1.3.2.1 Adhesion Ligands

1.3.2.2 Growth Factors and Cytokines

1.3.3 Engineering Physical Properties

1.3.3.1 Mechanics

1.3.3.2 Anisotropy

1.3.3.3 Porosity

1.3.3.4 Topography

1.3.4 Summary

1.4 Cellular Detection of the Microenvironment

1.4.1 Biochemical Signals

1.4.2 Biophysical Signals

1.4.2.1 Mechanotransduction

Role of Focal Adhesions

Role of Adherens Junctions

Integrative Pathways of Focal Adhesions and Adherens Junctions

1.5 Responding to the Microenvironment

1.6 Conclusion

References

Chapter 2: Functionalizing With Bioactive Peptides to Generate Bio-Instructive Scaffolds

2.1 Adhesion Molecules

2.1.1 Adhesion Receptors

2.1.2 Adhesion Receptor-Binding Peptides

2.2 Methods of Identifying Cell-Binding Peptides

2.3 Peptides in Tissue Engineering

2.3.1 Self-Assembled Peptide Scaffolds

2.3.2 Cell-Binding Peptides

2.3.2.1 RGD

2.3.2.2 GFOGER

2.3.2.3 REDV

2.3.2.4 KLPGWSG

2.3.2.5 DHLSDNYTLDHDRAIH

2.3.2.6 Summary

2.4 Conclusion

Acknowledgments

References

Part II: Bone

Chapter 3: Bio-Instructive Scaffolds for Bone Regeneration

3.1 Introduction

3.2 Commonly Used Linear Polymers in Bone Tissue Engineering

3.2.1 Natural Materials

3.2.1.1 Protein-Based Biomaterials

3.2.1.2 Polysaccharides-Based Biomaterials

3.2.2 Synthetic Polymers

3.2.2.1 Aliphatic Polyesters

3.2.2.2 Polyalcohols

3.2.2.3 Other Polyesters

3.2.2.4 Poly(Amino Acids)

3.2.2.5 Other Linear Polymers

3.2.3 Hybrid Materials

3.3 Interactions Between Materials and Cells

3.3.1 The Effect of Material Morphology on Cells: Geometry Sensing of the Surrounding Network

3.3.1.1 Porous Scaffolds

3.3.1.2 Hydrogels

3.3.1.3 Electrospun Fibers

3.3.1.4 Pattern

3.3.2 Other Factors

3.4 Bioactive Modification of Linear Polymers for Bone Regeneration

3.4.1 Delivery of Bioactive Substances

3.4.2 Surface Modification

3.5 Concluding Remarks

Acknowledgments

References

Part III: Tendon/Ligament

Chapter 4: Bio-Instructive Scaffolds for Tendon/Ligament Regeneration

4.1 Introduction

4.1.1 Anterior Cruciate Ligament: Physical Properties and Treatment Options

4.1.2 Tendon/Ligament Tissue Engineering

4.2 Synthetic Polymer Scaffolds

4.2.1 Linear Degradable Polymers

4.2.2 Braided Fibrous Scaffolds

4.2.2.1 Fabrication and Mechanical Response

4.2.2.2 In Vitro Outcomes

4.2.2.3 In Vivo Outcomes

4.2.2.4 Conclusions

4.2.3 Knitted Fibrous Scaffolds

4.2.3.1 Fabrication and Mechanical Response

4.2.3.2 In Vitro Outcomes

4.2.3.3 In Vivo Outcomes

4.2.3.4 Conclusions

4.2.4 Electrospun Nonwoven Micro-Fiber Networks

4.2.4.1 In Vitro Outcomes

4.2.4.2 In Vivo Outcomes

4.2.4.3 Conclusions

4.3 Bioactive Materials

4.3.1 Blending and Encapsulation

4.3.2 Adsorption

4.3.3 Conjugation

4.3.4 Conclusions

4.4 Composite Materials

4.5 Graded Materials

4.5.1 Bone Insertion Site

4.5.2 Muscle Attachment

4.5.3 Conclusions

4.6 Conclusions and Future Directions

References

Part IV: Cartilage

Chapter 5: Bio-Instructive Scaffolds for Cartilage Regeneration

5.1 Introduction

5.2 Structure and Function of Cartilage

5.3 Cells Used for Cartilage Regeneration

5.4 Growth Factors and Their Mechanisms That Effect Differentiation

5.5 ECM-Derived Scaffolds

5.6 Scaffolds Fabricated From Natural Polymers

5.7 Synthetic Polymer Scaffolds

5.8 Nanostructured Scaffolds

5.9 Maintenance of Neotissue

5.10 Conclusion

Acknowledgments

References

Part V: Muscle

Chapter 6: Ultrastructure and Biomechanics of Skeletal Muscle ECM: Implications in Tissue Regeneration

6.1 Skeletal Muscle Injury and Regenerative Strategy

6.2 Major Components of Skeletal Muscle ECM

6.2.1 The Epimysium

6.2.2 The Perimysium

6.2.3 The Endomysium

6.2.4 The Basement Membrane

6.3 Ultrastructure and Functionalities of the Skeletal Muscle ECM

6.3.1 Ultrastructure of Endomysial ECM and Its Force Transmission Role

6.3.2 Ultrastructure of Perimysial ECM and Its Interaction With Myocytes and Tendon

6.3.3 Epimysium ECM and Its Force Transmission Role

6.3.4 Ultrastructure of Basement Membrane and Its Binding Function

6.3.5 Biomechanical Functionalities of the Skeletal Muscle ECM

6.4 Biomechanical Properties of Skeletal Muscle and Skeletal Muscle ECM

6.4.1 Passive Biomechanical Properties of Skeletal Muscle

6.4.2 A Comparative Study Between Porcine Skeletal Muscle and Skeletal Muscle ECM

6.4.2.1 Sample Preparation

6.4.2.2 Mechanical Testing Protocols

6.4.2.3 Mechanical Properties of Skeletal Muscle and Skeletal Muscle ECM

6.4.2.4 A Few Discussion Points

6.5 The Implications in Skeletal Muscle Regeneration

6.5.1 Skeletal Muscle ECM as Graft Material

6.5.2 Acellular Skeletal Muscle ECM Hydrogel for Injection Therapy

6.6 Summary

Acknowledgment

References

Chapter 7: Bio-Instructive Scaffolds for Muscle Regeneration: NonCrosslinked Polymers

7.1 Skeletal Muscle Physiology

7.2 Scaffolds’ Materials and Fabrication Techniques

7.2.1 Synthetic Polymeric Materials

7.2.1.1 Polyesters

7.2.1.2 Polyurethanes

7.2.2 Fabrication Techniques

7.2.2.1 2D Topographical Configurations

Surface Patterning

Electrospinning

7.2.2.2 3D Topographical Configurations

Microgrooved

Porous Scaffolds

7.3 2D Topographical Configurations

7.3.1 2D Patterning

7.3.2 Electrospun Aligned Fiber Mats

7.4 3D Topographical Configurations

7.4.1 Microgrooved Scaffolds

7.4.2 Scaffolds With Aligned Pores

7.5 Conclusions

References

Chapter 8: Bio-Instructive Scaffolds for Skeletal Muscle Regeneration: Conductive Materials

8.1 Progress of Skeletal Muscle Tissue Engineering

References

Part VI: Musculoskeletal Interfaces

Chapter 9: Bio-Instructive Scaffolds for Musculoskeletal Interfaces

9.1 Background

9.2 Muscle Interfaces

9.2.1 Myotendinous Junctions 3D Scaffolds

9.2.2 Neuromuscular Junctions 3D Scaffolds

9.2.3 Vascularization

9.2.4 Conclusions

9.3 Cartilage Bone Interface Section

9.3.1 The Bone Cartilage Interface

9.3.2 Gradient Biomaterials

9.3.3 Tissue Adhesives

9.3.4 Composite and Drug Releasing Scaffolds

9.3.5 Scaffold-Free Constructs

9.3.6 Cell Sheet Technologies

9.3.7 Dual Phase Scaffolds

9.3.8 Conclusions

9.4 Bone:Tendon, Bone:Ligament Interface

9.4.1 Interface Anatomy

9.4.2 Stratified Scaffold Design

9.4.3 Cell Gradients

9.4.4 Material Gradients

9.4.5 Biochemical Gradients

9.4.6 Conclusions

9.5 Summary

References

Index

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