Enhancement of Endothelial Cell Retention on ePTFE Vascular Constructs by siRNA-Mediated SHP-1 or SHP-2 Gene Silencing

Abstract

Insufficient retention of endothelial cells to the luminal surface of small-diameter tissue engineered vascular grafts has precluded clinical translation. This study utilized a gene silencing strategy to enhance the adhesion strength of vascular endothelial cells to fibronectin-coated expanded polytetrafluoroethylene, a common vascular graft material. SHP-1 and SHP-2 are both phosphatases known to inhibit the formation of focal contacts. By employing siRNA to knockdown the expression of SHP-1 or SHP-2, we observed a significant improvement in cell retention following 6 h of pulsatile fluid shear stress. At an average fluid shear stress of 15 dyn/cm 2 , cell retention was improved from approximately 30% for control groups to approximately 70 and 85% for cells treated with SHP-1 and SHP-2 specific siRNA, respectively (n = 8 for all groups). We also observed that treatment with SHP-1 or SHP-2 specific siRNA caused a modest increase in focal contact density and did not cause a significant effect on the expression of the endothelial cell markers VEGFR-2, VE-cadherin, and PECAM-1. These findings indicate that molecular modulation may be an effective strategy for improving the retention of endothelial cells within tissue engineered vascular grafts, which may in turn improve their clinical performance.

Cell and nanoparticle transport in tumour microvasculature: the role of size, shape and surface functionality of nanoparticles

“…The IMFEM [78][79][80][81][82][83] is a computational framework to concurrently deal with the relevant physical interactions in biological environments [80,84,85], including fluid-structure interaction (FSI) [82,86,87], cell-cell interaction [81,88,89], thermal fluctuation [78,79,90], electrokinetics [83,91,92], self-assembly behaviour [79,[93][94][95] and other mesoscale and molecular effects [96]. In this work, the IMFEM will be used to simulate the blood flow as well as the microcirculation of NPs.…”