A hybrid vascular model biomimicking the hierarchic structure of arterial wall: Neointimal stability and neoarterial regeneration process under arterial circulation

Abstract

A layered-structure hybrid vascular graft, mimicking the hierarchic structure of the intima and media of a natural artery, is expected to exhibit antithrombogenicity and to accelerate neoarterial tissue formation. Two models of hybrid vascular grafts were prepared on knitted Dacron fabric grafts (inner diameter 4 mm, length 6 cm). Model I grafts consisted of an endothelial cell monolayer formed on collagenous matrix, and model II grafts consisted of an endothelial cell monolayer that formed on hybrid collagenous medial tissue in which smooth muscle cells were incorporated. Both models (n = 17 for each model) were implanted bilaterally in carotid arteries and left in place for up to 26 weeks. Although all of the implanted grafts were patent, the two models significantly differed in the degree of maturity of the regenerated neoarterial wall especially at earlier implantation periods. At 2 weeks, model II grafts showed a much higher degree of neointimal integrity than model I grafts: a smooth and organized neointimal layer was formed, which was free from leukocyte adhesion. On further increase of implantation time, the formation of neomedia (subendothelial smooth muscle cell layers) and circumferential orientation of both smooth muscle cells and collagenous extracellular matrix were much more advanced in model II grafts than in model I grafts. At 26 weeks after implantation, layered elastic laminae regenerated along circumferentially oriented smooth muscle cells in neomedia were observed only in model II grafts. Irrespective of model, little excessive smooth muscle cell proliferation occurred. A hierarchically structured hybrid graft eventually provided a more integrated neointimal layer and accelerated neoarterial tissue formation much more than model I grafts. The significance of the incorporation of smooth muscle cells into hybrid grafts is discussed.