## 6 Future Perspectives and Concluding Remarks  
In this review paper, we present the lower respiratory-physiology-on-a-chip and describe related research advances. Because of the current levels of environmental pollution, respiratory organs are threatened more than ever. Lower respiratory-physiology-on-a-chip have been developed and researched for the prevention and treatment of respiratory diseases. The developed chips are being studied in efforts to mimic tissue such that results can be applied to humans rather than using animal experiments. Vascularization of organ chips, which allows the mimicking not only of structural and mechanical properties but also immune responses and the internal networking of tissue, are a good example of these efforts. The research on vascularized respiratory chips is ongoing, and the prospects are bright. In order to manufacture a vascularized respiratory chip that more closely resembles human tissue, the following components are required. Most conventional respiratory chips have used cell lines or primary epithelial cell cultures. These have limited ability to reproduce the physiological characteristics of actual respiratory organs. It is necessary to mimic in vivo respiratory environments for disease modeling and drug testing. It should be possible to incorporate the structural, functional, and mechanical features of human respiratory epithelium along with the composition of various cells such as airway SMCs, fibroblasts, and immune cells. For this purpose, the utilization of patient-derived cells and organoids, an area of active research, may be considered a challenge. In most respiratory chip studies, cells have been cultured using coating materials such as collagen and fibronectin. However, the ECM in vivo is composed of various proteins, and the use of a single material limits the ability of the system to mimic cell-cell and cell-substrate interactions. Therefore, to study the drug reactivity and molecular features similar to the in vivo context, tissue-specific decellularized extracellular matrices can be applied to the chip to mimic the tissue microenvironment more accurately. The majority of lower respiratory-physiology-on-a-chip studies have fabricated chips using soft lithography. This method is advantageous in terms of mass production and precision, but it requires a high level of skill and time for mold making. For this reason, the use of 3D bioprinting technology that can produce chips in a shorter time period and facilitate flexibility in design changes represents an appealing alternative for the development of lower respiratory-physiology-on-a-chip. Many researchers have investigated the relationships between respiratory risk factors and lung disease using lower respiratory-physiology-on-a-chip. However, these systems have limits in their ability to mimic the respiratory microenvironment, such as the lack of vasculatures or of an air-liquid interface environment. When humans inhale harmful respiratory risk factors, the particles are filtered several times, with only tiny particles reaching the alveoli. Therefore, there may be errors in the results of the toxicity test in chip, currently used in the respiratory field. Therefore, future developments with lower respiratory-physiology-on-a-chip require an advanced vascularized respiratory-physiology-on-a-chip that implements blood flow along with a structural simulation of the respiratory system that is similar to the actual human body. All authors contributed to the writing of this manuscript. All authors have read and agreed to the published version of the manuscript. This work was partly supported by Institute for Information & communications Technology Promotion (IITP) grant funded by the Korea government (MSIP) (No.