The current generation of small caliber artificial vascular grafts occlude within a short period of time due to various problems involving blood-biomaterial interactions. One way of circumventing this is to introduce a monolayer of endothelial cells (EC) onto the graft before implantation to mimic a natural human vascular state. In this way, a hemostatic-thrombotic equilibrium can be maintained. Current methods used to transplant cells onto grafts include the pre-coating of grafts with extracellular matrix proteins like fibronectin and fibrin, as well as other methods like ammonia plasma surface modification of grafts. But little is known about the effects of surface modifications on ECs' ability to secrete prostacyclin (PGI2, anti-platelet thrombomodulators), tissue plasminogen activator (t-PA), and plasminogen activator inhibitor-1 (PAM, both fibrinolytic proteins). Our studies show that uncoated and fibronectin (fn) coated ammonia plasma modified poly(tetrafluoroethylene)(PTFE) are capable of secreting high amounts of PGI2. Furthermore, these surfaces secrete highly active t-PA proteins but relatively low amounts of PAI-1. Thus, uncoated and Fn coated modified PTFE support optimal conditions that provide for a non-thrombogenic surface, and may be suitable to further develop protocols and other strategies for arterial and venous reconstruction. Another strategy that we implemented was to further enhance the secretion of t-PA by EC. In this approach, we established a retroviral-mediated transfection protocol wherein human t-PA sequences encoded in a plasmid (PB2NSt) were stably integrated into the EC genome.
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:QMM.30692 |
| Date | January 1999 |
| Creators | Lu, Albert, 1974- |
| Contributors | Sipehia, Rajender (advisor) |
| Publisher | McGill University |
| Source Sets | Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
| Language | English |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Format | application/pdf |
| Coverage | Master of Science (Department of Physiology.) |
| Rights | All items in eScholarship@McGill are protected by copyright with all rights reserved unless otherwise indicated. |
| Relation | alephsysno: 001740530, proquestno: MQ64396, Theses scanned by UMI/ProQuest. |
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