Histologic Assessment of Drug-Eluting Grafts Related to Implantation Site
Résumé
Drug-eluting vascular prostheses represent a new direction in vascular surgery to reduce
early thrombosis and late intimal hyperplasia for small calibre grafts. Subcutaneous implantation in
rats is a rapid and cost-effective screening model to assess the drug-elution effect and could, to some
extent, be useful to forecast results for vascular prostheses. We compared biological and histological
responses to scaffolds in different implantation sites. Polycaprolactone (PCL), paclitaxel-loaded
PCL (PCL-PTX) and dexamethasone-loaded PCL (PCL-DXM) electrospun scaffolds were implanted
subcutaneously and in an infrarenal abdominal aortic model in rats for up to 12 weeks. At the
conclusion of the study, a histological analysis was performed. Cellular graft invasion revealed
differences in the progression of cellular infiltration between PCL-PTX and PCL/PCL-DXM groups in
both models. Cell infiltration increased over time in the aortic model compared to the subcutaneous
model for all groups. Cell counting revealed major differences in fibroblast, macrophage and
giant cell graft colonisation in all groups and models over time. Macrophages and giant cells
increased in the PCL aortic model; whereas in the subcutaneous model these cell types increased
only after three weeks or even decreased in the drug-eluting PCL groups. Other major findings were
observed only in the aortic replacement such as extracellular matrix deposition and neo-angiogenesis.
The subcutaneous implant model can be used for screening, especially when drug-eluting effects are
studied. However, major histological differences were observed in cell type reaction and depth of
cell penetration compared to the aortic model. Our results demonstrate that the implantation site is
a critical determinant of the biological response.
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