Airway smooth muscle--on-a-chip: a microfluidic approach to study alveolar smooth muscle remodelling

Abstract

Respiratory illnesses, like chronic obstructive pulmonary disease (COPD) and asthma, pose significant global health challenges due to their chronic nature and limited treatment options. Airway smooth muscle (ASM) plays a vital role in respiratory diseases, particularly in airway remodelling and obstruction. ASM, which encircles the bronchial tree and extends to the trachea, plays a vital yet not fully understood role in lung physiology. However, its dysfunction is strongly associated with asthma and COPD progression, leading to excessive contraction, increased inflammatory mediator release, and ASM hypertrophy. However, identifying its precise function is challenging due to limitations in existing research models for assessing ASM contraction. In vivo models offer a comprehensive physiological perspective but possess ethical concerns and they do not allow for the direct measurement of ASM contraction. Meanwhile, ex vivo and in vitro models provide a more direct assessment; however, they lack crucial physiological factors. Understanding how ASM cells interact with their surroundings is essential for gaining deeper insights into respiratory disorders. To address this gap, we aimed to mimic the human airway smooth muscle-on-a-chip model, incorporating ASM cells in a 3D microenvironment. This microfluidic platform provides a physiologically relevant environment, allowing for studying complex mechanisms that drive airway remodelling and dysfunction in respiratory diseases. The ASM-on-a-chip is designed for long-term 3D cell culture of ASM cells that reorient itself to form a smooth muscle fibre. The design provides side channels for manipulating the constituent of the hydrogel to study the effect of compounds on AMS remodelling.