###### Abstract  
Recently, respiratory systems are increasingly threatened by high levels of environmental pollution. Organ-on-a-chip technology has the advantage of enabling more accurate preclinical experiments by reproducing in vivo organ physiology. To investigate disease mechanisms and treatment options, respiratory-physiology-on-a-chip systems have been studied for the last decade. Here, we delineate the strategic approaches to develop respiratory-physiology-on-a-chip that can recapitulate respiratory system in vitro. The state-of-the-art biofabrication methods and biomaterials are considered as key contributions to constructing the chips. We also explore the vascularization strategies to investigate complicated pathophysiological phenomena including inflammation and immune responses, which are the critical aggravating factors causing the complications in the respiratory diseases. In addition, challenges and future research directions are delineated to improve the mimicry of respiratory systems in terms of both structural and biological behaviors.  
respiratory system; organ-on-a-chip; vascularization; biofabrication; extracellular matrix 2020 10 900 000 00.  
Extracellular matrix (ECM) has been studied to recapitulate the microenvironment closed to the native tissue and organ [6; 7]. Basically, cells are surrounded by a complex ECM for biochemical and mechanical interactions. It regulates cellular behaviors such as cell adhesion, growth, migration, differentiation, and function by controlling the focal adhesion and cytoskeletal dynamics [8]. ECM contains various proteins including fibronectin, collagen, and elastin. To mimic the ECM's role, biocompatible polymers like natural and synthetic polymer have been used [9].  
OoC are fabricated through various technologies to simulate the function of the tissue. There are critical effects on cell behaviors, so the trend is to implement the OoC in three dimensional (3D) rather than two dimensional (2D) [10]. Among the 3D fabrication technologies, the most widely used approach is the use of microfluidic chips to control the flow of fluid and air to provide OoC with a mechanical environment similar to that of the actual tissue [11].  
Vasculature plays an important role in mimicking living tissues. The vasculature is the pathway to transport nutrients, toxic substances, and body waste and they affect all cells in the body. The presence of appropriate vasculatures is critical to investigate complicate pathophysiological phenomena including inflammation and immune responses [12; 13]. In addition, by generating a flow in the vasculatures, a physiological motion can be provided to mimic the tissue fluid environment [14]. Accordingly, research on the fabrication and application of OoC incorporated vasculatures are being actively pursued [15].  
In this sense, we delineate the strategic approaches to develop respiratory-physiology-on-a-chip that can recapitulate respiratory system in vitro. The state-of-the-art biofabrication methods and biomaterials are considered as major contributions to building the chips. We also explore the vascularization strategies to investigate complicated pathophysiological phenomena including inflammation and immune responses, which are the critical aggravating factors that cause the complications in the respiratory diseases. In addition, challenges and future research directions are delineated to improve the mimicry of respiratory systems in both structural and biological behaviors.