3D Lung Models for Regenerating Lung Tissue

Front Cover
3D Lung Models for Regenerating Lung Tissue
Copyright Page
Contents
List of contributors
Preface
1 Is the lung a complex organ to rebuild?
Overview: the form, function, and beauty of the lung
The mucus barrier and lung sentinel immunity
The trachea and upper airways
The airway epithelium
Spatial organization of integrated innate and adaptive immunity in the lung
The lung circulation
Gas exchange: the core job of the lungs
Bioengineering in the lungs is key to function
The lung lymphatics
Testing lung function
The lung microbiome in normal lung homeostasis
References
I. 2D culture and the microenvironment
2 Two-dimensional cell culturing on glass and plastic: the past, the present, and the future
Definition of two-dimensional cell culturing
Glass: the two-dimensional surface in the beginning of cell culturing
Glass: a two-dimensional surface used today
Plastic for two-dimensional cell culturing
Hydrophilicity, surface chemistry, and cell attachment
Cells in two dimensions and three dimensions in the body and relevance for two-dimensional cell culturing
The impact of switching between different kinds of surfaces and the role of medium composition
Conclusions
References
3 The importance of lung microenvironment
Introduction
Collagen and fibril formation
Fibrillary collagens and fibril formation
Nonfibrillary collagens
Supportive glycoproteins
Elastin, fibrillin, and emilin
Laminin and the basement membrane
Fibronectin
Proteoglycans
Chondroitin sulfate/dermatan sulfate proteoglycans
Heparan sulfate proteoglycans
Keratan sulfate proteoglycan
Glycosaminoglycan structure and function
Chondroitin sulfate/dermatan sulfate
Heparan sulfate
Hyaluronan
Microenvironments
Cells in the microenvironments of the human lung
Fibroblasts
Conclusions
References
II. 3D lung models
4 The air–liquid interface model
Introduction
Lung structure and epithelium composition
Air–liquid interface models of the lung epithelium: what can we measure?
Single-cell RNA sequencing analysis of air–liquid interface–differentiated cell subtypes and states: how well do these repr...
Recapitulation of epithelial phenotype in air–liquid interface cultures from asthma patients
Recapitulation of epithelial phenotype in air–liquid interface cultures from chronic obstructive pulmonary disease patients
Use of air–liquid interface culture to study effects of environmental insults: respiratory virus
Use of air–liquid interface culture to study effects of environmental insults: cigarette smoke
Use of air–liquid interface culture to study effects of environmental insults: air pollution
Concluding remarks
References
5 Lung organoid models
Introduction
Mouse lung organoids
Human adult lung organoids
Human lung organoids—embryonic
iPSC-derived lung organoids
Disease models using lung organoids: chronic lung diseases
Fibrosis
COPD and emphysema
Disease models using lung organoids: genetic lung diseases
Cystic fibrosis
Hermansky-Pudlak syndrome
Disease models using lung organoids: viral lung infections
Conclusion
References
6 Biomaterials for in vitro models in lung research
Introduction to biomaterials
Brief history of biomaterials
Properties and types of biomaterials
Natural biomaterials
Synthetic biomaterials
Scaffold fabrication and modification strategies
Biomaterials for lung-related applications
Specific features of the lung
Biomaterials for healthy and diseased lung modeling
Biomaterials for organoid formation and engraftment
Biomaterials in air-liquid interphase cultures
New biomaterial-based strategies for modeling the lung microenvironment
Conclusions
References
7 Three dimensional lung models - Three dimensional extracellular matrix models
Introduction
Extracellular matrix changes in chronic lung diseases
Asthma
Chronic obstructive pulmonary disease
Idiopathic pulmonary fibrosis
Two-dimensional versus three-dimensional cell culture systems
Three-dimensional models—1: single-protein models
Collagen
Gelatin and methacrylated gelatin
Other extracellular matrix components
Three-dimensional models—2: extracellular matrix models with complex extracellular matrix mixtures
Decellularized lung scaffolds
Decellularized lung extracellular matrix–derived hydrogels
Challenges
Conclusions
References
8 Lung-on-chip
Introduction
Brief historical background of organ-on chip technology
Alveolus lung-on-chip models
Mimicking lung parenchymal diseases on-chip
Airway lung-on-chip models
Application of lung-on-chip disease models with a focus on regenerative medicine
Use of lung-on-chip models to study effects of environmental insults
Advantages and challenges of lung-on-chip technology
Concluding remarks
References
9 Mechanical stimuli in lung regeneration
Introduction
Stiffness of the cell microenvironment
Cell stretch
Cell shear stress
Microbioreactors for mechanically preconditioning lung cells
Mechanical stimuli in whole lung bioreactors
Conclusion
Funding
References
III. New directions
10 Advanced manufacturing: three-dimensional printing and bioprinting of models of lung and airways
Introduction
Design considerations for manufactured lung scaffolds
Biomaterials for manufacturing lung scaffolds
Natural materials
Synthetic materials
Hybrid materials
Manufacturing porous lung scaffolds
Casting
Self-assembly
Electrospinning
Manufacturing methods with true architecture control
3D printing
Bioprinting
Four-dimensional printing and responsive materials
Summary and future directions
References
11 Drug screening and high throughput in three-dimensional lung models
Introduction
The main difficulties associated with the identification of new pharmacological approaches
How three-dimensional models can help to overcome these problems
Target discovery
Improving physiological complexity
Recapitulating human biology
High-throughput screening and lead optimization
Phenotypic screening and drug repurposing
Absorption, distribution, metabolism and excretion and inhalation safety studies
Inhaled drugs
The role of three-dimensional in vitro models
Concluding statements
References
12 Model visualization: from micro to macro
Model validation: from micro to macro
Light versus electron microscopy
Light microscopy across scales
Imaging at the organelle level
Imaging at the organ level
Conclusion
References
13 Artificial intelligence and computational modeling
Introduction
Definition and history of artificial intelligence and machine learning
What is machine learning?
What is deep learning?
Machine learning in thoracic imaging
Computer-aided detection
Radiomics
Applications of machine learning in pulmonary diseases
Machine learning for lung cancer diagnosis
Deep learning model for airway localization
Deep learning model for classification of chronic obstructive pulmonary disease
Detection of Covid-19 on medical imaging
Challenges to further implementation of computer-aided diagnosis and radiomics
Conclusion
References
IV. Concluding remarks and future directions
14 Challenges and opportunities for regenerating lung tissue using three-dimensional lung models
Acknowledgments
Index
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