Haemodynamic Regulation of Gene Expression in Vascular Tissue Engineering

Dina      S. Vara; Geoffrey      Punshon; Kevin      M. Sales; George      Hamilton; Alexander      M. Seifalian

Abstract

Synthetic grafts, namely expanded polytetrafluoroethlene (ePTFE) and poly(ethylene terephthalate) (Dacron), used for cardiovascular bypass surgery are thrombogenic. Lining the inner lumen (“seeding”) of synthetic grafts with endothelial cells (ECs) increases patency rates similar to those of autologous grafts (e.g. saphenous vein). The major drawback with seeding grafts is the retention of cells present on the graft after implantation in vivo, where large portions of cell wash off. Preconditioning the seeded EC monolayer with shear stress has been shown to promote the reorganisation of the EC cytoskeleton and production of extracellular matrix, resulting in higher EC retention after exposure to blood flow. Vascular ECs have a number of essential and complex roles. ECs synthesise and secrete vasoconstrictors, vasodilators, growth factors, fibrinolytic factors, cytokines, adhesion molecules, matrix proteins and mitogens that modulate many physiological processes such as wound healing, haemostasis, vascular remodelling, inflammatory and immune responses. Vascular cells in vivo are exposed to haemodynamic forces created by the pulsatile flow of blood through the vessel. Due to their unique anatomical position, ECs are constantly exposed to shear stress forces and allow the vessel wall to adapt to changes by modulating EC structure and function. This review describes the mainly in vitro and in vivo studies used to define the molecular role haemodynamics have in vascular disease and its usage in developing tissue engineered vascular bypass grafts.

Keywords: Endothelial cells, shear stress, drug delivery, biomaterials, gene expression, patency, intimal hyperplasia

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