SHEAR STRESS-CONDITIONED, ENDOTHELIAL CELL-SEEDED VASCULAR GRAFTS - IMPROVED CELL ADHERENCE IN RESPONSE TO IN-VITRO SHEAR-STRESS

Background. Prosthetic vascular grafts with adherent endothelial cell monolayers may prove useful for small-caliber vessel bypass. However, endothelial cells adhere poorly to prosthetic graft material, and they are stripped when exposed to in vivo shear stress. This study sought to determine whether in vitro shear stress conditioning improves endot helial cell adhesion and decreases thrombogenicity of endothelial cell -seeded grafts. Methods. The lumens of 1.5 mm (inside diameter) spun;b olyurethane polymer vascular grafts were seeded with bovine aortic end othe[ial cells and cultured in vitro for 6 days with or without contin uous laminar shear stress, first at I to 2 dynes/cm(2) for 3 days, the n at approximately 25 dynes/cm(2) for 3 days. Grafts preconditioned by shear stress and the static control grafts were then exposed to arter ial shear stress at 25 dynes/cm(2) for 25 seconds. The number of dislo dged cells was counted, and the grafts were examined by light and scan ning electron microscopy. Whole blood clotting time in the grafts was also determined. Results. Exposure of grafts to acute shear stress dis lodged 1.35 x 10(6) +/- 0.44 x 10(6) cells from static grafts compared with 1.05 x 10(4) +/- 0.16 x 10(4) cells from grafts preconditioned b y shear stress. By light and electron microscopy an intact endothelial monolayer was observed to cover the lumen of shear stress-conditioned grafts, whereasfew cells remained on the luminal surface of grafts no t previously exposed to shear stress. The clotting time in shear stres s-conditioned grafts was significantly prolonged in relation to grafts not exposed to shear stress. Conclusions. These findings show that en dothelial cell adhesion and retention on vascular grafts in vitro is m arkedly enhanced by preconditioning the seeded endothelial cell monola yer with long-term shear stress. Consequently, vascular grafts contain ing shear stress-conditioned endothelial monolayers are less thromboge nic in vitro than small-caliber vascular grafts without intact endothe lial cell monolayers.