An In Vitro Microfluidic Alveolus Model to Study Lung Biomechanics

Abstract

The gas exchange units of the lung, the alveoli, are mechanically active and undergo cyclic deformation during breathing. The epithelial cells that line the alveoli contribute to lung function by reducing surface tension via surfactant secretion, which is highly influenced by the breathing-associated mechanical cues. These spatially heterogeneous mechanical cues have been linked to several physiological and pathophysiological states. Here, we describe the development of a microfluidically assisted lung cell culture model that incorporates heterogeneous cyclic stretching to mimic alveolar respiratory motions. Employing this device, we have examined the effects of respiratory biomechanics (associated with breathing-like movements) and strain heterogeneity on alveolar epithelial cell functions. Furthermore, we have assessed the potential application of this platform to model altered matrix compliance associated with lung pathogenesis and ventilator-induced lung injury. Lung microphysiological platforms incorporating human cells and dynamic biomechanics could serve as an important tool to delineate the role of alveolar micromechanics in physiological and pathological outcomes in the lung.

Biomimetic and soft lab-on-a-chip platform based on enzymatic-crosslinked silk fibroin hydrogel for colorectal tumor model

“…The chip was stretched, bent, and twisted without breaking or damaging the inner channel for at least 3 days when kept in medium or PBS to avoid dehydration (Figure 4 A) (see supplementary info ). This deformation ability could be optimal in a myriad of tissue models, such as lung, heart and colon, which present dynamic stretching movements (30,31). Moreover, this opens the way to deepen mechanobiology studies in the field of cancer.…”

Self-assembled innervated vasculature-on-a-chip to study nociception

“…Such devices can serve as invaluable tools for understanding the molecular mechanism underlying pain as well as platforms for testing therapeutics and analgesics. Besides leveraging the perfusable vascular network to examine the effect of bloodborne factors on nociception, microfluidic-assisted microphysiological systems are ideally poised to incorporate dynamic mechanical cues [66][67][68][69] as well as vascular specific functions such as vasodilation; all these microenvironmental cues are important in nociception [70,71].…”

The breathtaking world of human respiratory in vitro models: Investigating lung diseases and infections in 3D models, organoids, and lung‐on‐chip

“…Microphysiological systems (Table 1) composed of interacting organs-on-chip or connected 3D tissue constructs provide more physiologically relevant alternatives to monolayer cultures or animal studies, in particular if studying the interactions of human pathogens at barrier sites. In vitro microfluidic models of the upper and lower respiratory tract [19] down to the alveolus, including dynamic biomechanics to mimic respiration and/or vascularization [15]. These microfluidic organ-on-chips show continuous development and enable inclusion of physical, mechanical, and organizational features of the respiratory tract/lung microenvironment [16][17][18].…”