Engineering Translational Models of Lung Homeostasis and Disease / edited by Chelsea M. Magin.

Format:

Book

Contributor:

Magin, Chelsea M., editor.

Series:

Advances in Experimental Medicine and Biology, 2214-8019 ; 1413

Language:

English

Subjects (All):

Regenerative medicine.

Biomedical engineering.

Cytology.

Biomaterials.

Cells.

Biotechnology.

Regenerative Medicine and Tissue Engineering.

Biomedical Engineering and Bioengineering.

Cell Biology.

Biomaterials-Cells.

Local Subjects:

Regenerative Medicine and Tissue Engineering.

Biomedical Engineering and Bioengineering.

Cell Biology.

Biomaterials-Cells.

Biotechnology.

Biomaterials.

Physical Description:

1 online resource (328 pages)

Edition:

1st ed. 2023.

Place of Publication:

Cham : Springer International Publishing : Imprint: Springer, 2023.

Summary:

Cutting-edge engineering approaches towards modelling lung homeostasis and disease have created dynamic new opportunities for interdisciplinary collaboration and unprecedented progress toward understanding and treating lung disease. This text connects established research in lung biology and physiology to innovative engineering strategies for pulmonary modelling. This unique approach aims to encourage and facilitate progress among a greater audience of basic and translational scientists, clinicians, and medical practitioners. Engineering Translational Models of Lung Homeostasis and Disease illustrates the advances in lung tissue characterization, revealing dynamic changes in the structure, mechanics, and composition of the extracellular matrix. This information paves the way for tissue-informed engineering models of pulmonary tissue, improved design of clinical materials, and advances against a variety of common pathologies. Current translational challenges arehighlighted, as are engineering opportunities to overcome these barriers. This foundational text holds valuable lessons for researchers and clinicians throughout the fields of engineering, materials science, cell biology, pulmonary medicine, and clinical science. Chapter 4 is available open access under a Creative Commons Attribution 4.0 International License via link.springer.com.

Contents:

Intro

Foreword

Preface

Contents

Chapter 1: An Introduction to Engineering and Modeling the Lung

1.1 Introduction

1.2 Broader Impacts of Understanding Lung Biology in Health and Disease

1.3 Lung Physiology in Homeostasis and Disease

1.4 Engineering Translational Models of Lung Homeostasis and Disease

1.5 Conclusion

References

Part I: Engineering and Modeling the Developing Lung

Chapter 2: Simple Models of Lung Development

2.1 Introduction

2.1.1 Basics of Lung Development

2.2 Models to Study Lung Development

2.3 Models of Early Lung Development (Airways)

2.3.1 Explant Cultures

2.3.2 2D and 3D Imaging of Branching Morphogenesis

2.3.3 Time-Lapse Imaging

2.3.4 Organoids

2.4 Models of Late Lung Development

2.4.1 Saccular Phase Models

2.4.2 Alveologenesis

2.4.3 Other 3D Models of Alveologenesis

2.5 Conclusion

Chapter 3: Lung Development in a Dish: Models to Interrogate the Cellular Niche and the Role of Mechanical Forces in Development

3.1 Introduction

3.2 Self-Assembled Organoid and Spheroid Models

3.2.1 Creating Lung Organoid Models That Represent Regional Composition and Heterogeneity

3.2.2 Advancing the Complexity of Organoids to Investigate Tissue Crosstalk

3.2.3 Induction of Lung Organoids to Create Multiple Tissue Compartments

3.3 Microfluidic and Organ-on-a-Chip Models to Study Lung Development

3.3.1 Moving Toward More Complex Physiology with Multiple Channels

3.3.2 Integration of Dimensionality and Biomaterials into Organ-on-a-Chip Platforms

3.4 Whole Organ Models to Understand the Mechanics of Lung Development

3.5 Conclusion

Chapter 4: Multipotent Embryonic Lung Progenitors: Foundational Units of In Vitro and In Vivo Lung Organogenesis

4.1 Introduction

4.2 Overview of Embryonic Lung Progenitors.

4.2.1 Stage-Specific Epithelial Progenitors (Primordial, Distal Tip, Basal)

Lung Primordial Progenitors

Distal Tip Progenitors

Airway Basal Cells

4.2.2 Stage-Specific Mesenchymal Progenitors

4.3 Ex Vivo Culture of Multipotent Embryonic Lung Progenitors

4.3.1 Ex Vivo Culture of Mouse Embryonic Progenitors

4.3.2 Ex Vivo Culture of Human Embryonic Progenitors

4.4 In Vitro Derivation of Multipotent Embryonic Lung Progenitors

4.5 Progenitor Cell Similarity Models

4.6 Conclusion

Part II: Engineering and Modeling Large Airways

Chapter 5: Basic Science Perspective on Engineering and Modeling the Large Airways

5.1 Introduction

5.2 Proximal Airways: Composition and Function

5.3 Regeneration of the Airways

5.3.1 Endogenous Stem Cells

5.3.2 The Stem Cell Niche

5.3.3 Stem Cell Attrition with Disease and Aging

5.4 Developing Cellular Therapies for Regeneration of Airway Tissues

5.5 In Vitro Models of the Human Airways

5.5.1 Transwell Air-Liquid Interface (ALI) Cultures

5.5.2 Airway Spheroids: Tracheo/Bronchospheres

5.5.3 Organoids

5.5.4 Lung-on-a-Chip

5.5.5 Xenografts

5.6 Cell-Matrix Interactions

5.7 Conclusion

Chapter 6: Computational, Ex Vivo, and Tissue Engineering Techniques for Modeling Large Airways

6.1 Large Airways: Structure-Function Relationship

6.2 Pathologies and the Need for Modeling the Large Airways

6.2.1 Conditions That Cause Large Airway Dysfunction

6.2.2 Need for Computational and Physiological Models of the Large Airways

6.3 Computational Modeling

6.4 Ex Vivo Testing

6.5 Tissue Engineering Techniques for Modeling the Large Airways

6.5.1 Biomaterial Scaffolds

Decellularized Scaffolds

Cellular, Synthetic, or Hybrid Biomaterial Approaches

6.5.2 Manufacturing Techniques for Large Airway Models.

6.6 Tools for Functional Assessment of Large Airway Models

6.7 Limitations and Future Considerations

Chapter 7: Engineering Large Airways

7.1 Introduction

7.2 Forces During Respiration and How They Can Influence Construct Design

7.3 The Structure of the Trachea and Its Mechanical Properties

7.3.1 Tracheal Cartilage

7.3.2 Trachealis Muscle

7.3.3 Annular Ligament

7.4 Mechanical Properties of the Whole Trachea and the Implications of Mechanical Property Mismatch

7.4.1 Compliance

7.4.2 Extension and Bending

7.5 Key Considerations and Summary of Recommended Mechanical Tests

7.6 Conclusion

Part III: Engineering and Modeling the Mesenchyme and Parenchyma

Chapter 8: Engineering and Modeling the Lung Mesenchyme

8.1 Introduction

8.2 Advancing the Discovery of Fibroblast Heterogeneity

8.3 The Organization and Heterogeneity of Lung Fibroblasts

8.3.1 Platelet-Derived Growth Factor Receptor Alpha (PDGFRα)-Expressing Alveolar Fibroblasts 1 and 2

8.3.2 Platelet-Derived Growth Factor Beta (PDGFRβ)-Expressing Pericytes

8.3.3 Airway and Vascular Smooth Muscle (ASM and VSM)

8.4 Other Fibroblast Subtypes

8.4.1 Developmental Secondary Crest Myofibroblasts (SCMF)

8.4.2 Fibrotic Disease-Associated Myofibroblasts (MyoF)

8.5 Bioengineering Approaches to Characterize Complex Fibroblast Behaviors

8.5.1 Organoids to Model Mesenchymal-Epithelial Interactions

8.5.2 Lung-on-a-Chip to Model Human Lung Architecture and Environmental Forces

8.5.3 Acellular Tissue Scaffolds to Model Fibroblast and ECM Interactions

8.6 Targeting Fibroblasts with Nanoparticles as Strategy for Intervention

8.7 Conclusion

Chapter 9: Engineering Dynamic 3D Models of Lung

9.1 Introduction

9.2 Building the Extracellular Microenvironment

9.2.1 Biomaterials.

9.2.2 Lung Decellularization and Recellularization

9.2.3 dECM Hydrogels

9.2.4 Synthetic Hydrogels

9.2.5 Hybrid-Hydrogels

9.3 Constructing Relevant Tissue Geometries

9.3.1 Precision-Cut Lung Slices

9.3.2 Organoids

9.3.3 Engineered 3D Hydrogel Constructs

9.3.4 3D Bioprinting

9.4 Incorporating Dynamic Mechanical Forces

9.4.1 Biomechanical Modeling

9.4.2 Lung-on-a-Chip

9.5 Conclusion

Chapter 10: Lung-on-a-Chip Models of the Lung Parenchyma

10.1 Introduction

10.2 Lung Alveolar Cells and the Alveolar Environment

10.2.1 Lung Alveolar Cells and Their Environment

10.2.2 Lung Alveolar Epithelial Cells In Vitro

10.3 Reproducing the Alveolar Barrier with a Lung-on-a-Chip

10.3.1 Reproducing the Lung Alveolar Environment on Chip

Scaffolds for the Alveolar Barrier: Engineering a Thin, Flexible and Soft Basement Membrane

Mechanical Stress Induced by the Respiratory Movements

10.3.2 Effects of Biochemical and Physical Cues on the Lung Alveolar Barrier

Effects of Mechanical Forces on Alveolar Epithelial Cells

Effects of Mechanical Forces on Lung Endothelial Cells

Lung Alveolar Extracellular Matrix (ECM)

Effects Induced by the Air-Liquid Interface

10.3.3 Read-Outs: Extracting Information from a Lung-on-a-Chip

10.4 Lung Disease-on-a-Chip Models

10.4.1 Idiopathic Pulmonary Fibrosis (IPF)

10.4.2 Emphysema

10.4.3 Acute Respiratory Distress Syndrome (ARDS)

10.4.4 COVID

10.4.5 Lung Adenocarcinoma

10.5 Challenges of Lung-on-a-Chip Technologies

10.6 Perspectives for Lung-on-a-Chip Technologies

Chapter 11: Assessment of Collagen in Translational Models of Lung Research

11.1 Introduction

11.2 Quantification of Collagen

11.2.1 The Sircol Assay

11.2.2 Hydroxyproline Quantification

11.2.3 Immuno-Based Methods.

11.3 Mass Spectrometry Characterization of Collagen

11.3.1 Assessment of Collagens in Proteomics Analyses of Pulmonary ECM

11.3.2 Analysis of Posttranslational Modifications of Collagen

11.3.3 Assessment of Enzymatic Crosslinks in Collagen

11.4 Assessment of Collagen Architecture In Situ

11.4.1 Masson's Trichrome Staining

11.4.2 Picrosirius Red Staining

11.4.3 Second Harmonic Generation Microscopy

11.4.4 Immunohistochemistry

11.4.5 Transmission Electron Microscopy

11.4.6 Selected Complementary and Emerging Techniques

Confocal Reflection Microscopy (CRM)

Atomic Force Microscopy (AFM)

Imaging Probes for Magnetic Resonance Imaging (MRI)

11.5 Monitoring Fibril Formation in Real Time Using Purified Collagen

11.6 Assessment of Collagen Turnover by Peripheral Markers

11.7 Conclusion

Part IV: Engineering and Modeling the Pulmonary Vasculature

Chapter 12: Understanding and Engineering the Pulmonary Vasculature

12.1 Pulmonary Vasculature in Development and Diseases

12.2 Pulmonary ECs and Their Angiocrine Functions

12.3 Engineering the Pulmonary Vasculature

12.3.1 Generation of Vascularized Organoids

12.3.2 Bioengineered Lung and Vasculature Using Acellular Native Lung Scaffold

12.3.3 Vascularized Lung-on-a-Chip

12.3.4 Guided Vascularization Through 3D Bioprinting

12.4 Pulmonary Vascular Diseases

12.5 Conclusion

Chapter 13: An Overview of Organ-on-a-Chip Models for Recapitulating Human Pulmonary Vascular Diseases

13.1 Introduction

13.2 Microfluidics and Organ-on-a-Chip

13.2.1 Concepts

Microfluidics in Vascular Biology

Patterning Microvascular Networks

13.3 OoC for Pulmonary Vascular Diseases

13.4 Conclusion

Chapter 14: Clinical Translation of Engineered Pulmonary Vascular Models

14.1 Introduction.

14.2 Brief Overview of Pulmonary Vascular Physiology.

Notes:

Includes bibliographical references.

ISBN:

9783031266256