DISSECTING THE ROLE OF TOPOGRAPHICAL CUES IN ENDOTHELIALIZATION PROCESS

Abstract

A major challenge in the treatment of cardiovascular disease is graft failure due to late endothelialization of small synthetic vascular grafts. Although several biochemical and mechanical strategies have been applied to promote endothelialization of the graft surfaces, enhancement of implant endothelialization has been limited. The integrity of Endothelial Cells (ECs) monolayer is crucial for endothelialization, but the understanding of the crosstalk between surface modification and cell-cell connectivity is still limited. Toward a more effective approach to enhance endothelialization, in this thesis a combined strategy making use of both topographical features and biochemical perturbations was investigated. The effect of micron-scale anisotropic topography on ECs behaviors is analyzed in conjunction with pharmacological perturbations of EC junctions regulators. We identified a protein tyrosine phosphatase, PTP1B, as a potent regulator of ECs junction stability. Our results showed that PTP1B inhibition synergized with grating topographies to modulate EC adherens junction’s rearrangement resulting in global EC monolayer sheet orientation, connectivity, and migration. Our data suggest utilizing grating topographies and PTP1B inhibitor together as a possible platform to enhance endothelialization of vascular grafts.