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Open AccessArticle

Histologic Assessment of Drug-Eluting Grafts Related to Implantation Site

Division of Clinical Pathology, University Hospital of Geneva, Geneva 1211, Switzerland
School of Pharmaceutical Sciences, University of Geneva, Geneva 1211, Switzerland
Department of Pharmacy-Drug Sciences, University of Bari “Aldo Moro“, Bari 70125, Italy
Department of Cardiovascular Surgery, Faculty of Medicine, University Hospital, Geneva 1211, Switzerland
Author to whom correspondence should be addressed.
Academic Editors: Robin Muise-Helmericks and Andy Wessels
J. Dev. Biol. 2016, 4(1), 11;
Received: 30 November 2015 / Revised: 10 February 2016 / Accepted: 16 February 2016 / Published: 20 February 2016
(This article belongs to the Special Issue Wound Healing and Tissue Regeneration)
PDF [3549 KB, uploaded 20 February 2016]


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. View Full-Text
Keywords: vascular prosthesis; tissue engineering; extracellular matrix; drug release; biodegradable polymers; foreign body reaction; pathology vascular prosthesis; tissue engineering; extracellular matrix; drug release; biodegradable polymers; foreign body reaction; pathology

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Tille, J.-C.; De Valence, S.; Mandracchia, D.; Nottelet, B.; Innocente, F.; Gurny, R.; Möller, M.; Walpoth, B.H. Histologic Assessment of Drug-Eluting Grafts Related to Implantation Site. J. Dev. Biol. 2016, 4, 11.

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