Please use this identifier to cite or link to this item:
https://hdl.handle.net/2440/105894
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Type: | Journal article |
Title: | Evaluation of synthetic vascular grafts in a mouse carotid grafting model |
Author: | Chan, A. Tan, R. Michael, P. Lee, B. Vanags, L. Ng, M. Bursill, C. Wise, S. |
Citation: | PLoS One, 2017; 12(3):e0174773-1-e0174773-15 |
Publisher: | Public Library of Science |
Issue Date: | 2017 |
ISSN: | 1932-6203 1932-6203 |
Editor: | Jourd'heuil, D. |
Statement of Responsibility: | Alex H.P. Chan, Richard P. Tan, Praveesuda L. Michael, Bob S.L. Lee, Laura Z. Vanags, Martin K.C. Ng, Christina A. Bursill, Steven G. Wise |
Abstract: | Current animal models for the evaluation of synthetic grafts are lacking many of the molecular tools and transgenic studies available to other branches of biology. A mouse model of vascular grafting would allow for the study of molecular mechanisms of graft failure, including in the context of clinically relevant disease states. In this study, we comprehensively characterise a sutureless grafting model which facilitates the evaluation of synthetic grafts in the mouse carotid artery. Using conduits electrospun from polycaprolactone (PCL) we show the gradual development of a significant neointima within 28 days, found to be greatest at the anastomoses. Histological analysis showed temporal increases in smooth muscle cell and collagen content within the neointima, demonstrating its maturation. Endothelialisation of the PCL grafts, assessed by scanning electron microscopy (SEM) analysis and CD31 staining, was near complete within 28 days, together replicating two critical aspects of graft performance. To further demonstrate the potential of this mouse model, we used longitudinal non-invasive tracking of bone-marrow mononuclear cells from a transgenic mouse strain with a dual reporter construct encoding both luciferase and green fluorescent protein (GFP). This enabled characterisation of mononuclear cell homing and engraftment to PCL using bioluminescence imaging and histological staining over time (7, 14 and 28 days). We observed peak luminescence at 7 days post-graft implantation that persisted until sacrifice at 28 days. Collectively, we have established and characterised a high-throughput model of grafting that allows for the evaluation of key clinical drivers of graft performance. |
Keywords: | Carotid Arteries Tunica Intima Myocytes, Smooth Muscle Animals Mice, Inbred C57BL Mice, Transgenic Disease Models, Animal Hyperplasia Collagen Actins Polyesters Green Fluorescent Proteins Microscopy, Electron, Scanning Luminescent Measurements Blood Vessel Prosthesis Vascular Patency Female Vascular Grafting Neointima Cell Tracking |
Rights: | © 2017 Chan et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
DOI: | 10.1371/journal.pone.0174773 |
Grant ID: | http://purl.org/au-research/grants/nhmrc/1066174 |
Published version: | http://dx.doi.org/10.1371/journal.pone.0174773 |
Appears in Collections: | Aurora harvest 8 Medicine publications |
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hdl_105894.pdf | Published Version | 2.3 MB | Adobe PDF | View/Open |
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