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.
Healing of biomaterial implants varies depending on the type and structure of material and the tissue surrounding the implant. In this study we examined structural differences of 30 microm, 60 microm, and 100 microm expanded polytetrafluoroethylene (ePTFE) using scanning electron microscopy, and we also investigated differences in healing for these three different porosity ePTFE grafts implanted within subcutaneous tissue and adipose tissue. Scanning electron microscopic examination of 30 microm, 60 microm, and 100 microm ePTFE revealed structural differences and differences in fiber density within the internodal space. Circular patches (6 mm in diameter) of 30 microm ePTFE were implanted within subcutaneous tissue and epididymal fat pads of male Sprague-Dawley rats. After 5 weeks, the implants were removed and analyzed for fibrous capsule formation, endothelialization, and for activated monocytes and macrophages in association with the material. Histological evaluation revealed dense fibrous capsule formation surrounding only the 30 microm ePTFE subcutaneous implants. From immunohistochemistry data obtained, we generated an Endothelialization Index (measure of neovascularization) and a Monocyte/Macrophage Index (measure of inflammatory response) for each sample. Consistently, 60 microm ePTFE had the greatest Endothelialization Index at both implant sites while 100 microm ePTFE generally had the largest values for the Monocyte/Macrophage Index. These data indicate that both the structure of the material and the site of implant influence the healing characteristics of ePTFE and suggest that activated monocytes and/or macrophages associated with the implant may inhibit endothelialization of ePTFE.
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