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International Journal of Bioprinting dECM bioink for in vitro disease modeling

thereby successfully forming a vascular network where because of the inclusion of a vascular structure, it is
microvessels are interconnected. An in vitro vascularized possible for the model to be connected with other organs
airway model containing a multilayered cell structure of the respiratory system and contribute to the overall
was successfully fabricated after integrating the epithelial research related to tracheal disease.
and vascular parts. Judging based on the functional While numerous models have been created using 3D
activation of the cells constituting the models, tmdECM bioprinting and diverse hydrogels, such as airway-derived
is more suitable than Matrigel, which is widely used in dECMs, to effectively replicate numerous aspects of the
fabricating in vitro respiratory models, for simulating the respiratory system in vitro, several areas still require further
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airway-specific microenvironment. Moreover, asthma- improvement and practical implementation. Recently, Park
specific features were well expressed in the disease model, et al. demonstrated the swift production of a multilayer
as confirmed by the secretion of inflammatory cytokines. structure of the respiratory system using extrusion-based
This study is significant because it used a tmdECM bioink 3D bioprinting. The recent 3D-bioprinted respiratory
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and 3D bioprinting to create a model that precisely features models focus on featuring the simulation of more complex
the airway-specific microenvironment and mimics the respiratory structures using various respiratory cells and
functions of most airways, and showed that the model is the integration of different cell types to realistically mimic
applicable for investigating asthma, which is an airway- physiological characteristics. However, the current 3D
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specific disease. However, the model has limitations in that bioprinting technology is not capable of rapid creation of
it does not have an airflow structure, and the inflammatory a respiratory structure encompassing cells and an airflow
response cannot be precisely simulated owing to the absence passage on one single platform and has limited strength in
of inflammatory cells. Nevertheless, this study showcases a simulating respiratory function, including gas exchange.
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pioneering in vitro model that features an airway-specific Additionally, since most respiratory diseases have a
microenvironment and can aid the development of new fundamental link with the immune system, including an
asthma therapies and related research. etiological connection with microorganisms, it becomes
Nam et al. fabricated tmdECM and VdECM bioinks, in evident that a 3D bioprinting technology that can integrate
which they encapsulated epithelial and endothelial cells, and immune cells and microbial composition to build a model is
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with which they fabricated normal in vitro tracheal models urgently needed. Recently, Cho et al. developed a blood-
using extrusion-based 3D bioprinting (Figure 4D). They lymphatic-integrated in vitro model using 3D bioprinting
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developed cylindrical airway vascular structures via coaxial and successfully implemented the vascular system and
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bioprinting using a sacrificial layer. This printing method immune system on one platform. However, there has yet
is suitable for reproducing normal vascular structures to be an attempt to combine respiratory cells within a lung
because it can mimic the shapes of real vascular structures model; thus, it is necessary to secure cell lines that can be
and adjust the structure’s diameter. A module containing used for 3D bioprinting and develop technology that can
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tracheal epithelial cells was combined with this vascular produce a model in one step in a short time. 224
structure to create the resultant in vitro tracheal model. Additionally, more precise recapitulation of the
In this model, tracheal epithelial cells formed an epithelial microenvironment in respiratory models is warranted.
barrier, and treatment with IL-13 induced an inflammatory In particular, the respiratory system functions in a
response. In particular, immune cell transmigration and dynamic environment. To reflect this, Sengupta et al.
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infiltration occurred in the monocyte/macrophage lineage have recently created a model equipped with electro-
cells that flowed with the media through the blood vessels. pneumatic devices and used elastic silicone to observe
This is representative of the airway immune response to physiological responses on the platform under changing
exposure to an inflammatory environment. In this pressure conditions. Nevertheless, to simulate a dynamic
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study, a trachea-specific microenvironment was precisely environment, a bioreactor that can mimic gas dynamics
created using tmdECM, VdECM bioink, and advanced 3D and control pressure and can reproduce various dynamic
bioprinting. Additionally, the inflammatory mechanism in characteristics of the respiratory system and realistic chest
the 3D-bioprinted cylindrical matured vascular structure movements must be developed in the future. Combining
could be precisely simulated by flushing immune cells the bioreactor with a 3D-printed airway model can create
with medium. However, this structure did not possess a microenvironment that better resembles the actual
trachea-specific microbial composition and was unable to respiratory system. To more accurately mimic pulmonary
simulate air flow, which is the main function of the trachea. function, it is essential to incorporate methods such as
Nevertheless, this study developed an advanced in vitro sensors for real-time assessment of functional respiration,
model that reflects the airway-specific microenvironment gas exchange, and mucosal movement into the bioreactor.
and overall tracheal multilayer structure. Moreover, With the real-time evaluation results, operational errors of

Volume 10 Issue 2 (2024) 150 doi: 10.36922/ijb.1970