Development of a small diameter (<6 mm) synthetic vascular graft with clinically acceptable patency must overcome the inherent thrombogenicity of polymers and the development of neointimal thickening. Establishment of an endothelial cell lining on the lumenal surface has been hypothesized as a mechanism to improve the function of vascular grafts. The major aim of this study was to evaluate the use of laminin type 1, covalently bound to all surfaces of ePTFE grafts on neovascularization of the interstices and lumenal surface endothelialization. One mm i.d. vascular grafts were surface modified through covalent attachment of laminin type 1. Grafts were subsequently implanted as interpositional aortic grafts in rats. Following five weeks implantation the grafts were explanted and morphologically evaluated using scanning electron microscopy and light microscopy. Scanning electron microscopy identified an extensive coverage of antithrombogenic cells on the lumenal flow surface of laminin type 1 modified grafts. Histological evaluation confirmed the presence of endothelial cells on the mid-graft lumenal surface of laminin 1 modified grafts. Extensive neovascularization of the interstices of the laminin modified grafts occurred as compared to control grafts. We conclude that surface modification using laminin type 1 accelerates both the neovascularization and endothelialization of porous ePTFE vascular grafts.

The chronic inflammatory response associated with the abluminal surface of polymeric vascular grafts has been suggested to affect adversely graft neovascularization, the cellular response at the luminal surface of vascular grafts, and overall graft patency. To better understand the source for this chronic inflammation, this study examined two types of macrophages and the amount of cellular proliferation around two widely used graft materials, expanded polytetrafluoroethylene (ePTFE) and polyethyleneterephthalate (PET or Dacron) implanted in the rat for 3 and 5 weeks. Serial sections of explants were analyzed for recruited macrophages (ED1), resident macrophages (ED2), and proliferating cells (PCNA). Results show that Dacron is more inflammatory than ePTFE and that there is a segregated macrophage response; the first 54 micrometer of perigraft tissue were composed predominantly of recruited macrophages (ED1+) while the more distal tissue consisted of resident macrophages (ED2+). Proliferating cells were located predominantly in this same 54 micrometer perigraft region. In subcutaneous tissue they accounted for 23% of all cells present around Dacron after 3 weeks of implantation and 8% after 5 weeks. Conversely, cellular proliferation around ePTFE increased from 4% at 3 weeks to 21% at 5 weeks. In adipose tissue, proliferation levels around the implanted polymers were lower and more similar after 3 and 5 weeks. Serial sections revealed the coordinate expression of PCNA and ED1 antigens by the same individual cells, suggesting that proliferation is a mechanism used to perpetuate the chronic inflammatory response. These results suggest a new target for designing treatments to alter inflammation and improve the healing associated with these biomaterials.

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