A newly devised hybrid small-caliber graft was developed. The graft consisted of three components: a microporous polyurethane graft (inside diameter 3 mm; length 5 cm) with compliance close to that of a natural artery; an artificial basement membrane composed of a complex gel of type I collagen and dermatan sulfate, which showed enhanced adhesion and growth of endothelial cells (ECs) and reduced adhesion of platelets in vitro; and an autogenous EC monolayer with high degrees of cell-substrate and cell-cell interactions, which was performed before implantation. Twenty EC-seeded grafts were implanted bilaterally into carotid arteries of dogs without anticoagulant. The implantation period was up to 26 weeks. The overall patency rate for seeded grafts was 75%. The percentage of endothelial coverage of seeded grafts was 98% as implanted, 92% at 2 weeks, and 100% after 12 weeks. The mean intimal thickness of grafts was around 80 microns at 12 weeks. Little additional increase was observed at 26 weeks. It appears that the complete endothelialization as implanted, high cell-to-substrate adhesive strength that resists hydrodynamic shear stress, and biomechanical compatibility of the polyurethane graft functioned cooperatively to provide a vascular graft with high antithrombogenicity and minimal hyperplasia. The integrated approach of combining biomechanical and cellular engineering designs leading to an important functional smaller-caliber graft is discussed.