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International Journal of Bioprinting dECM bioink for in vitro disease modeling

Additionally, many research teams have created high- of complex structure seen in the respiratory system and
fidelity liver models, which enable accurate and rapid drug the in vitro configurations of various respiratory cells for
screening. However, these models do not recapitulate the creating the models. Previous studies have demonstrated
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liver-specific microenvironment. Therefore, hydrogels such using Transwell and in vitro models to generate air–liquid
as dECM bioink that can simulate liver microenvironment interface (ALI) models, which possess multilayered
while maintaining high fidelity are promising ingredients structures composed of various alveolar cells on one
for making liver models. Additionally, automated platform. 205-208 Of particular importance, several studies
bioprinting technologies and advanced control systems have created models that simultaneously mimic repetitive
must be introduced to increase efficiency and improve breathing motion as well as blood and air flow, using
result consistency. flexible biomaterials and by means of photolithography-
based microfabrication. 209,210
4.4. Respiratory tissue-derived decellularized
extracellular matrix The in vitro respiratory models should not only mimic
Nasal meatus, airways, trachea, and lung are the structural features, but also reproduce the interactions
representative tissues and organs of the respiratory between immune cells and microbial ecosystem in the
system, whose most important function is to facilitate respiratory system. However, the existing, conventional
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the exchange of oxygen and carbon dioxide. Respiratory models have limitations in portraying interplay between
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the microenvironment of respiratory system and the
diseases include infectious diseases (e.g., pneumonia ), external environment. 211,212 These models are also not
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airway-related diseases (e.g., asthma, COPD ), and useful for studying pathophysiological mechanisms behind
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malignant tumors. Chronic respiratory diseases can the pathogenesis of asthma and COPD. Therefore, in vitro
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develop into fibrosis, leading to organ failure. Since models are urgently needed for therapy testing and disease
there is no perfect treatment for these diseases, it is investigation. 213,214 One solution is to use airway-derived
necessary to develop new treatments for respiratory dECM as a bioink for 3D bioprinting to mimic the airway-
diseases and efficient in vitro respiratory models for specific microenvironments and pathophysiological
research and drug testing. 199 environments of airway diseases. Unlike conventional
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The development of conventional in vitro respiratory manufacturing methods, 3D bioprinting is suitable for
model entails a step of culturing respiratory cells in two precise airway simulation because it can manufacture
dimensions. For example, this can be achieved with co- multilayered cellular structures and simultaneously enable
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culturing methods of respiratory epithelial cell lines and fluid and air flows on a single platform. 215,216 This allows
endothelial cells, or air–liquid interface (ALI) culture 3D-bioprinted models to precisely reproduce the complex
methods. These traditional in vitro models are relatively 3D structure and microenvironment of the airway,
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easy to set up, and the experimental conditions are easy more closely reflecting the pathophysiology of various
to control. They are also relatively inexpensive compared respiratory diseases and making research results more
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with other models and are suitable for conducting basic realistic. In particular, it can more effectively mimic the
research on respiratory system function and physiology. role of the immune system and inflammatory response,
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However, the 2D culture is unable to produce 3D enabling a better understanding of the mechanisms of
structure and to simulate the functional interactions of progression of respiratory diseases and the development of
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the lung; additionally, it faces challenges in reproducing treatment strategies.
complex physiological functions, such as gas exchange The importance of 3D bioprinting is exemplified
and respiratory movements. Additionally, it does by an in vitro respiratory model fabricated through 3D
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not sufficiently mimic the role of the immune system bioprinting using airway-derived dECM bioink. Park et al.
and inflammatory response. To address these issues, developed a tracheal mucosa-derived dECM (tmdECM)
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various 3D in vitro respiratory models have been created. bioink, in which they encapsulated epithelial cells and
An effective in vitro respiratory model should possess fibroblasts, and with which they fabricated an in vitro
multilayer structure made of the epithelium, basement normal vascularized airway model by means of extrusion-
membrane, and endothelium, and should be able to based 3D bioprinting (Figure 4C). Additionally, an in
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carry out the repetitive contraction and relaxation for gas vitro asthma model has been created by treating a normal
exchange. 195,202 Air and blood flows are also important model with interleukin-13 (IL-13), an asthma-inducing
features of the model. To incorporate these features in the factor. To create a vascular part, 3D bioprinting was
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model, flexible biomaterials must be used in the fabrication utilized to fabricate a vascular scaffold incorporating
of the in vitro model. The characteristics mentioned vascular cells. After undergoing a maturation process,
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above reflect the requirements to realize the generation the scaffold was induced to generate microvessels,
Volume 10 Issue 2 (2024) 149 doi: 10.36922/ijb.1970