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Physiological vessel on chip model with integrated flow and oxygen control for in vitro small pulmonary artery studies

Huisman, Janet (2021) Physiological vessel on chip model with integrated flow and oxygen control for in vitro small pulmonary artery studies.

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Abstract:Oxygen tension and shear stress are believed to play a crucial role in the development of various vascular diseases such as pulmonary arterial hypertension. Since no physiological in vitro model yet exists to study the effect of these stimuli on the behaviour of patient-specific vascular cells, the aim of this research was to develop a three dimensional (3D) small pulmonary artery on chip (sPAoC) model with integrated flow and oxygen control. The proposed design consists of an oxygen impermeable microfluidic chip in which oxygen tension and flow rate can be controlled to mimic both the small pulmonary artery and the surrounding alveoli. The vessel is formed via displacement of collagen by a less viscous fluid (viscous finger patterning) to obtain a perfusable 3D collagen lumen in which human induced pluripotent stem cell (hiPSC) derived endothelial cells (ECs), smooth muscle cells and fibroblasts can be cultured. Although earlier characterization of these h iPSC-ECs revealed an immature arterial/venous phenotype, their response to hypoxia was found to be similar to primary pulmonary arterial ECs, providing previously unknown information about the current phenotype of the hiPSC-ECs. Additionally, a concept version of the chip system was fabricated without the alveolar compartment and imaging confirmed successful formation of cylindrical lumens in these chips with an average diameter of 313 ± 34 μm and a success rate of 90%. Finally, oxygen sensor spots and unidirectional flow were successfully integrated in this chip system. Together these initial results demonstrate the possibilities of the proposed sPAoC model for analysis of the vascular behaviour in response to stimuli such as (patho)physiological oxygen tensions and shear stresses.
Item Type:Essay (Master)
Faculty:TNW: Science and Technology
Subject:44 medicine
Programme:Nanotechnology MSc (60028)
Link to this item:http://purl.utwente.nl/essays/88710
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