Development of a hierarchically structured hybrid vascular graft biomimicking natural arteries

A hierarchically structured hybrid vascular graft, resembling the layered structure of the intima and the media of a natural artery, is expected to exhibit structural stability and function similar to those of an artery. Two models of hybrid vascular grafts were constructed on knitted Dacron grafts (internal diameter, 4 mm; length, 6 cm; Golaski Laboratories, Inc., Philadelphia, PA) in vitro. The model I graft consisted of only an endothelial cell (EC) monolayer, and the model II graft was hierarchically structured with an EC monolayer and smooth muscle cell (SMC) multilayers embedded in a mixed gel of type I collagen and dermatan sulfate. Both models were implanted bilaterally in carotid arteries of 11 dogs for up to 12 weeks without anticoagulant. All grafts were patent after the implantation. There was a marked difference in the formation of the neomedia between the two models at 2 weeks: only a collagenous layer was observed beneath the EC monolayer in model I grafts, whereas the reconstructed neomedia consisting of proliferating SMCs and extracellular matrix was observed in model II grafts. In model I grafts at 2 weeks, the luminal surface with a wavelike form, along with crimps of the vascular graft, was almost endothelialized, but EC orientation was disorganized at the troughs of the crimps. Leukocyte adhesion on ECs and migration into their interstices were observed in some areas. Such events were infrequent in model II grafts at 2 weeks. Model II grafts at 12 weeks had an integrated neomedia comparable to that of a natural artery: SMCs exhibited dense accumulation and circumferential orientation.(ABSTRACT TRUNCATED AT 250 WORDS)