2021/04/21 | Research | In-vitro & Organs-on-Chip

A 3D in-vitro model of the lung microvasculature

Up to date, researchers mostly use 2D cell culture platforms to study the biology of the vasculature of the lung. Now the ARTORG Organs-on-Chip Technologies laboratory, in collaboration with the Max-Delbrück Center in Berlin and the Departments of Pneumology and Thoracic Surgery of Bern University Hospital, has developed a more in vivo-like 3D model, which can be exposed to mechanical cyclic stretch, such as that induced by the breathing motions.

Left: schematic of a blood vessel in static mode (top) and cyclically stretched (bottom). The effect of 3D cyclic stretch on vascular remodeling in vitro can be seen. Endothelial cells align and create a tight barrier (middle and right bottom). Red: F-actin, Blue: DAPI (ARTORG Center, https://aip.scitation.org/doi/10.1063/5.0010159)

In the lung, small blood vessels and capillaries continuously experience cyclic mechanical strain resulting from the rhythmic breathing motions and from the intraluminal blood pressure. These mechanical forces deform these vessels and alter the physiology, morphology, biochemistry and gene expression of endothelial cells. However, the exact mechanisms of the mechanical signal transduction into biological responses remain to be clarified.

Existing in vitro models used to investigate the effect of mechanical stretch on endothelial layers are limited to two-dimensional cell culture platforms, which poorly mimic the typical three-dimensional structure of the vessels. For this reason, the ARTORG Center has developed a new perfusable 3D vasculature model on a chip.

One of the major findings of this study is that a 3D microvasculature can be exposed to a much higher mechanical cyclic stress level than previously reported with 2D models without any dysfunction of the endothelial barrier. These new results corroborate clinical data from the literature obtained with computed tomography. This new model thus mimics the in-vivo situation more closely than standard 2D models and in addition demonstrates that the dynamic breathing movements is an important parameter of the cellular environment.