LAUSR

Abstract Introduction: In addition to mechanical forces caused by blood flow, lung vascular networks undergo additional forces in the form of cyclic stretch from respiration. These forces act on the microvascular wall and play an important role in the regulation of vascular structure. Local changes in the mechanical microenvironment lead to functional changes in the system. However, the mechanisms by which the mechanical stretch is transduced into cellular signals remain to be clarified. Advanced in vitro platforms, better mimic the in vivo conditions and offer a potential alternative to traditional animal experiments. Objective: We developed a dynamic microvasculature platform to investigate the effect of 3D cyclic stretch of the rhythmic breathing movements on human microvascular remodelling, sprouting and barrier regulation. Results: A perfusable microvasculature was reproduced in the fibrinogen layer in by seeding Human Umbilical Vascular Endothelial Cells in a tube formed by a needle that was removed after gelation of the fibrinogen. The microvasculature was subjected to a 3D cyclic strain with magnitude of 8-10%. Consequently, low magnitude cyclic stretch increased the integrity of the barrier, decreased the size and number of gaps in the microvessel wall, and significantly decreased permeability coefficient of in vitro microvasculature Conclusion: Dynamic conditions appear to improve the integrity of the microvasculature, by aiding in the formation of tighter vessel walls, with smaller gaps sizes. This research may result in the development of novel therapeutic approaches in the treatment of pathologic conditions such as pulmonary hypertension and ventilator-induced lung injury.