## 4 Vascular Respiratory-Physiology-On-A-Chip
### Vascular Respiratory-Physiology-On-A-Chip
#### 4.3.2 Airway-On-A-Chip  
The trachea is a tubular structure that connects the larynx to the bronchi. The trachea branches vertically down the front of the esophagus, splitting into the left and right bronchus. These are the pathways that takes air in and out. In addition, when a substance from outside enters, the airway cilia function to discharge the extrinsic substance. [PERSON] et al. [33] succeeded in mimicking the structure and functions of the human airway in vitro and modeling disease and inflammatory responses. They used soft lithography to fabricate  
Figure 1: Vascularized lung-on-a-chip. All chip with two channels cultured of epithelial and endothelial cells that are separated by a stretching porous membrane. (**a** and **b**) Successfully co-cultured patient-derived human primary alveolar type I and type II-like epithelial cells and pulmonary endothelial cells on this lung-on-chip for over several days. This system is meaningful for the ability to mimic the in vivo environment using actual patient-derived lung epithelial cells. (**c**) In order to mimic the human lung, the upper chamber supports the growth of human lung alveolar epithelial cells and was filled with air, while the lower chamber cultivates pulmonary microvascular endothelial cells and was filled with liquid. (**a**) Reproduced with permission from [31]. Copyright © 2001 ROYAL SOCIETY OF CHEMISTRY (**b**) Reproduced with permission from [72]. Copyright © 2018 Springer Nature. (**c**) Reproduced with permission [73]. Copyright © 2017 John Wiley and Sons. \begin{table}
\begin{tabular}{c c c c} \hline \hline
**Couting Material** & **Cell Population** & **Features** & **Ref.** \\ \hline Fibronectin or collagen & Human alveolar epithelial cells and microvascular endothelial cells & Stretchable microfluidic system & [32] \\ Fibronectin or gelatin and & Bronchial epithelial cells & epithelial cells, & Stretchable microfluidic system & [31] \\ collagen1 & primary HUVECs & & \\ Fibronectin and collagen IV/1 & Bronchial epithelial 16 HEHE-cells, primary human alveolar epithelial cells & Stretchable microfluidic system & [72] \\ Fibronectin and collagen I & Human umbilical vein endothelial cells from pooled donors, primary alveolar epithelial cells containing type I and II cells & Microfluidic system & [73] \\ \hline \hline \end{tabular}
\end{table} 
Table 3: Vascular lung-on-a-chip. a microfluidic device that included an upper airway channel along with a microvascular channel. To mimic the physiological microenvironment of the native tissue, human alveolar epithelial cells were cultured in the upper airway and human pulmonary microvascular endothelial cells were used on opposite sides. They were also able to independently control various system parameters to reproduce complex integrated organ-level responses. The mechanical strain increases the uptake of nanoparticles and stimulates their transport into microvascular channels. [PERSON] et al. [74] used 3D printing to fabricate an airway-on-a-chip comprising the human alveolar epithelial type II cell line A549 and the EA.hy926 hybrid human cell line derived by fusing human umbilical vein endothelial cells (HUVEC) with A549 cells on the commercial transwells (Figure 2). The use of 3D bioprinting technology enables the automated and reproducible creation of thin and homogeneous cell layers and complex cell-cell interactions. These studies showed that the vascularized airway-on-a-chip by 3D bioprinting more faithfully reflects the structural and functional resemblance of the actual tissue. [PERSON] et al. [75] applied 3D bioprinting to simply and quickly construct a chip. To mimic the microenvironment of a trachea, decellularized trachea ECM bioink was used for printing. The primary human tracheal epithelial cells (hTEpCs) were seeded onto the vitrified membrane by decellularized trachea ECM on a transwell. Human extracellular microvascular endothelial cells (hDMEC) and lung fibroblasts were encapsulated and printed within designated polycarprolactone (PCL) frames using decellularized trachea ECM bioink.