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J. Dev. Biol. 2016, 4(1), 11; doi:10.3390/jdb4010011

Histologic Assessment of Drug-Eluting Grafts Related to Implantation Site

1
Division of Clinical Pathology, University Hospital of Geneva, Geneva 1211, Switzerland
2
School of Pharmaceutical Sciences, University of Geneva, Geneva 1211, Switzerland
3
Department of Pharmacy-Drug Sciences, University of Bari “Aldo Moro“, Bari 70125, Italy
4
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
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)
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Abstract

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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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

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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J. Dev. Biol. EISSN 2221-3759 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
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