NATURALLY PRODUCED EXTRACELLULAR-MATRIX IS AN EXCELLENT SUBSTRATE FORCANINE ENDOTHELIAL-CELL PROLIFERATION AND RESISTANCE TO SHEAR-STRESS ON PTFE VASCULAR GRAFTS

Purpose: Successful development of a vascular prosthesis lined with en dothelial cells (EC) may depend on the ability of the attached cells t o resist shear forces after implantation. The present study was design ed to investigate EC detachment from extracellular matrix (ECM) precoa ted vascular prostheses, caused by shear stress in vitro and to test t he performance of these grafts in vivo. Methods: Bovine aortic endothe lial cells were seeded inside untreated polytetrafluoro-ethylene (PTFE ) vascular graft (10 x 0.6 cm), PTFE graft precoated with fibronectin (FN), or PTFE precoated with FN and a naturally produced ECM (10(6) ce lls/graft). Sixteen hours after seeding the medium was replaced and un attached cells counted. The strength of endothelial cell attachment wa s evaluated by subjecting the grafts to a physiologic shear stress of 15 dynes/cm(2) for 1 h. The detached cells were collected and quantita ted. PTFE or EC preseeded ECM coated grafts were implanted in the comm on carotid arteries of dogs. Results: While little or no differences w ere found in the extent of endothelial cell attachment to the various grafts (79%, 87% and 94% of the cells attached to PTFE, FN precoated P TFE, or FN+ECM precoated PTFE, respectively), the number of cells reta ined after a shear stress was significanly increased on ECM coated PTF E (20%, 54% and 85% on PTFE, FN coated PTFE, and FN+ECM coated PTFE, r espectively, p <0.01). Implantation experiments in dogs revealed a sig nificant increase in EC coverage and a reduced incidence of thrombus f ormation on ECM coated grafts that were seeded with autologous sapheno us vein endothelial cells prior to implantation. Conclusion: ECM coati ng significantly increased the strength of endothelial cell attachment to vascular prostheses subjected to shear stress. The presence of adh esive macromolecules and potent endothelial cell growth promoting fact ors may render the ECM a promising substrate for vascular prostheses.