4.4 Article

A Novel Ovine ex vivo Arteriovenous Shunt Model to Test Vascular Implantability

Journal

CELLS TISSUES ORGANS
Volume 195, Issue 1-2, Pages 108-121

Publisher

KARGER
DOI: 10.1159/000331415

Keywords

Animal model; Cardiovascular endothelium; Cardiovascular system; Mechanobiology; Methods of evaluation; Tissue engineering; Vascular biology; Small intestinal submucosa; Thrombogenicity

Funding

  1. National Institutes of Health [R01 HL086582]
  2. New York State Stem Cell Science Foundation (NYSTEM) [C024316]

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The major objective of successful development of tissue-engineered vascular grafts is long-term in vivo patency. Optimization of matrix, cell source, surface modifications, and physical preconditioning are all elements of attaining a compatible, durable, and functional vascular construct. In vitro model systems are inadequate to test elements of thrombogenicity and vascular dynamic functional properties while in vivo implantation is complicated, labor-intensive, and cost-ineffective. We proposed an ex vivo ovine arteriovenous shunt model in which we can test the patency and physical properties of vascular grafts under physiologic conditions. The pressure, flow rate, and vascular diameter were monitored in real-time in order to evaluate the pulse wave velocity, augmentation index, and dynamic elastic modulus, all indicators of graft stiffness. Carotid arteries, jugular veins, and small intestinal submucosa-based grafts were tested. SIS grafts demonstrated physical properties between those of carotid arteries and jugular veins. Anticoagulation properties of grafts were assessed via scanning electron microscopy imaging, en face immunostaining, and histology. Luminal seeding with endothelial cells greatly decreased the attachment of thrombotic components. This model is also suture free, allowing for multiple samples to be stably processed within one animal. This tunable (pressure, flow, shear) ex vivo shunt model can be used to optimize the implantability and long-term patency of tissue-engineered vascular constructs. Copyright (C) 2011 S. Karger AG, Basel

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