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International Journal of Bioprinting 3D-bioprinted multicellular lung organoids

2. Organoids within the alveoli and are primarily responsible for the
production and secretion of surfactant, which reduces
2.1. Lung structure and cellular function surface tension within the alveoli to prevent collapse. In
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The lungs are intricately structured and play a crucial addition, AT2 cells have the potential to differentiate into
role in the gas exchange processes essential to our body. type I cells when necessary, thereby playing a critical role
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This vital function is enabled by the unique anatomical in lung tissue repair and regeneration. The surfactant
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architecture and complex cellular composition of the lungs, production and regenerative capabilities of AT2 cells are
which are divided into distinct parts: airways, alveoli, and essential for maintaining overall lung health (Figure 1A). 31
blood vessels, with each component made up of highly
specialized cells. The primary gas exchange occurs in Fibroblasts provide structural support to lung tissue
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the alveoli, where a variety of cells and blood vessels, such by producing fibrous proteins such as collagen and elastin,
as alveolar type I (AT1) cells, alveolar type II (AT2) cells, and are crucial for maintaining the elasticity and structural
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fibroblasts, and vascular endothelial cells (ECs), perform integrity of the lungs. However, excessive activation or
essential roles. 24 abnormal proliferation of fibroblasts can lead to diseases
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such as pulmonary fibrosis. Pulmonary fibrosis involves
AT1 cells cover most of the alveolar wall and are flat the abnormal hardening and functional degradation of lung
and thin, maximizing the efficiency of gas exchange. Their tissue, primarily caused by the overactivity of fibroblasts.
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extremely thin cell membranes allow oxygen and carbon ECs are essential for maintaining lung function by
dioxide to move rapidly between the blood and the alveoli. optimizing gas exchange in the lungs, regulating the
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While AT1 cells are essential for efficient gas exchange, they transfer of substances between blood and tissue, and
have limited regenerative capabilities. Therefore, recovery modulating inflammatory responses and blood clotting
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from damage to these cells can be slow and sometimes (Figure 1B). In particular, disruption of the blood-air
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incomplete, complicating lung repair processes. AT2 cells barrier due to damage or dysfunction of endothelial cells
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play a critical role in regulating the microenvironment can be associated with a variety of pathological conditions,

Figure 1. Schematic of lung cellular function and lung organoid. The structure of the lung is largely composed of alveolar type I (AT1) cells, alveolar
type II (AT2) cells, fibroblasts, and vascular endothelial cells (ECs). Each cell has a unique function and regulates the microenvironment within the
lung parenchyma. Generally, lung organoids are developed by harnessing the differentiation of only AT1 and AT2 cells, whereas organoids containing
fibroblasts and ECs are constructed using 3D bioprinting. This diagram was created with BioRender.com.

Volume 10 Issue 6 (2024) 3 doi: 10.36922/ijb.4092