Independent application of pressure and shear stress on endothelial cells in controlled bioreactors Federico Vozzi 1 , Francesca Bianchi 2 , Arti Ahluwalia 2 , Claudio Domenici 1 1) Biomimetic Materials and Tissue Engineering Laboratory, CNR Institute of Clinical Physiology, Via G. Moruzzi 1, Pisa, Italy 2) Research Center “E. Piaggio”, University of Pisa, Via Diotisalvi 2, Pisa, Italy Abstract The principal physical forces exerted on the blood vessel wall by the passage of intra-luminal blood are pressure and shear. In order to analyze their independent effects, these two stresses were applied to cultured cells by means of two different bioreactors: the Pressure Controlled Bioreactor (PCB) and the Laminar Flow Bioreactor (LFB), in which controlled levels of pressure and shear stress can be respectively generated. Using the bioreactor systems, Endothelin-1 and Nitric Oxide release from human umbilical vein endothelial cells (HUVEC) were measured in varying conditions of shear stress and pressure. As result, a decrease of Endothelin-1 production from the cells cultured in both bioreactors, with respect to the controls, was observed, whereas Nitric Oxide synthesis was up-regulated only in the presence of shear stress but not modulated by hydrostatic pressure. These results show that the two hemodynamic forces acting on blood vessels affect endothelial cell function in different ways, and that both should be considered when planning in vitro experiments in the presence of flow.