title: Evaluation of synthetic vascular grafts in a mouse carotid grafting model.
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.
authors.affiliation: The Heart Research Institute, Sydney, New South Wales, Australia.|Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia.
authors.forename: Alex H P
authors.identifier: http://orcid.org/0000-0002-1244-7673
authors.initials: AH
authors.lastname: Chan
authors.affiliation: The Heart Research Institute, Sydney, New South Wales, Australia.|Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia.
authors.forename: Richard P
authors.initials: RP
authors.lastname: Tan
authors.affiliation: The Heart Research Institute, Sydney, New South Wales, Australia.|Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia.
authors.forename: Praveesuda L
authors.initials: PL
authors.lastname: Michael
authors.affiliation: The Heart Research Institute, Sydney, New South Wales, Australia.
authors.forename: Bob S L
authors.initials: BS
authors.lastname: Lee
authors.affiliation: The Heart Research Institute, Sydney, New South Wales, Australia.|Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia.
authors.forename: Laura Z
authors.initials: LZ
authors.lastname: Vanags
authors.affiliation: The Heart Research Institute, Sydney, New South Wales, Australia.|Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia.|Royal Prince Alfred Hospital, Sydney, New South Wales, Australia.
authors.forename: Martin K C
authors.initials: MK
authors.lastname: Ng
authors.affiliation: The Heart Research Institute, Sydney, New South Wales, Australia.|Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia.
authors.forename: Christina A
authors.initials: CA
authors.lastname: Bursill
authors.affiliation: The Heart Research Institute, Sydney, New South Wales, Australia.|Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia.|School of Life and Environmental Sciences, University of Sydney, Sydney, New South Wales, Australia.
authors.forename: Steven G
authors.initials: SG
authors.lastname: Wise
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D001807:Blood Vessel Prosthesis; D002339:Carotid Arteries / Q000601:surgery*; D058948:Cell Tracking / Q000379:methods; D003094:Collagen / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006965:Hyperplasia; D008163:Luminescent Measurements / Q000379:methods; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008855:Microscopy, Electron, Scanning; D032389:Myocytes, Smooth Muscle / Q000378:metabolism; D058426:Neointima / Q000378:metabolism / Q000473:pathology; D011091:Polyesters / Q000737:chemistry; D017539:Tunica Intima / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D058017:Vascular Grafting / Q000379:methods*; D014654:Vascular Patency
chemical_list: D000199:Actins; D011091:Polyesters; D049452:Green Fluorescent Proteins; C016240:polycaprolactone; D003094:Collagen