Phenotypic modulation of smooth muscle cells in intima-media incorporated hybrid vascular prostheses

Hierarchical hybrid vascular grafts were constructed with an endothelial cell (EC) monolayer and hybrid medial layer composed of smooth muscle cells (SMCs) and type I collagen gel. The grafts, implanted into canine carotid arteries for up to 12 weeks, were ultrastructurally examined with a transmission electron microscope. Before implantation, SMCs incorporated into hybrid media were round and intracellularly filled with synthetic organelles such as rough endoplasmic reticula, mitochondria, free ribosomes, and Golgi complexes. Two weeks after implantation, bipolar spindle shaped SMCs still remained in a synthetic phenotype. At 12 weeks, circumferentially aligned SMCs were abundant in contractile apparatus such as myofilaments, dense bodies, and basement membranes. In a morphometric evaluation, the populations of three phenotypic SMCs (synthetic, intermediate, and contractile SMCs) were quantified. At 2 weeks, the proportions were 50.5, 41.8, and 7.7% for synthetic, intermediate, and contractile phenotypes, respectively. At 12 weeks, they were 9.9, 26.2, and 63.8%. These findings indicated that SMCs incorporated into hybrid grafts were transformed from a synthetic to a contractile phenotype under pulsatile stressed conditions after 12 weeks in vivo. Thus, the intima/media incorporated hybrid graft reconstructed a vessel wall similar to a native one in terms of structure and function.