Study Effects of Drug Treatment and Physiological Physical Stimulation on Surfactant Protein Expression of Lung Epithelial Cells Using a Biomimetic Microfluidic Cell Culture Device

Abstract

This paper reports a biomimetic microfluidic device capable of reconstituting physiological physical microenvironments in lungs during fetal development for cell culture. The device integrates controllability of both hydrostatic pressure and cyclic substrate deformation within a single chip to better mimic the in vivo microenvironments. For demonstration, the effects of drug treatment and physical stimulations on surfactant protein C (SPC) expression of lung epithelial cells (A549) are studied using the device. The experimental results confirm the device’s capability of mimicking in vivo microenvironments with multiple physical stimulations for cell culture applications. Furthermore, the results indicate the critical roles of physical stimulations in regulating cellular behaviors. With the demonstrated functionalities and performance, the device is expected to provide a powerful tool for further lung development studies that can be translated to clinical observation in a more straightforward manner. Consequently, the device is promising for construction of more in vitro physiological microenvironments integrating multiple physical stimulations to better study organ development and its functions.

Transwell Insert-Embedded Microfluidic Devices for Time-Lapse Monitoring of Alveolar Epithelium Barrier Function under Various Stimulations

“…Furthermore, a biomimetic microfluidic device capable of reconstituting physiological physical microenvironments in the lungs during fetal development for cell culture is developed. The device can be exploited to investigate effects of drug treatment and physical stimulation on surfactant protein expression of lung epithelial cells [ 22 ].…”

Editorial for the Special Issue on Organs-on-Chips

“…Since the cost of drug discovery is constantly increasing due to the limited predictability of conventional monolayer culture methods and animal models, this technology has great potential to promote drug discovery and development as well as to model human physiology and disease.This Special Issue is themed to provide insight and advancements in organ-on-chip microdevices. There are fifteen papers including three review papers, covering a novel material to fabricate microfluidic organs-on-chips [1], methods to deliver mechanical stimuli [2,3], methods to measure mechanical forces [4,5], methods to evaluate cellular functions in 3D cultures [6][7][8], and specific organ models; lung chips [3,9], liver chips [10,11], blood vessel chips [12][13][14][15] including models of the outer blood-retina barrier [14] and ischemia-reperfusion injury [15].Inside the body, cells are exposed to biomechanical forces, including fluidic shear stress and mechanical strain, which regulate cell function and contribute to disease. Kaarj et al reviewed methods to produce mechanical stimuli focusing on the technical details of devices [2].…”

“…This paper shows organ-on-chip systems that incorporate various types of mechanical stimuli and their potential applications to develop physiologically relevant models and to study mechanobiology. Lin et al developed a simple yet powerful microfluidic device that can generate hydrostatic pressure and cyclic strain to mimic the lung physiological microenvironment [3]. This device paves the way to better understand the cellular behaviors under various lung physiological conditions for future translational studies.…”