Grant: Strategic Projects - Group

Vascular diseases are the first cause of hospitalization in industrialized countries. Their total cost to the Canadian economy is estimated at $19 billion. Current therapies to treat occluded vessels include surgical bypass and autologous grafting, or implantation of intravascular stents. Both polyester fabric (PET, DacronTM) and fluoropolymer membrane (ePTFE, Gore-TexTM) grafts have shown to perform well for grafts of diameter larger than 6 mm. However, no material has been demonstrated to be suitable for small-diameter (< 6 mm) applications because of significant problems associated with compliance mismatch and thrombogenicity. Therefore, replacement of small-diameter vessels is a significant unmet medical need and the focus of this proposal. The main hypotheses, that were partially validate in previous work, of the current project are: Innovative non-woven polymeric structures may display mechanical properties similar to those of small arteries; Smooth muscle cell (SMC) and endothelial cell (EC) growth on these new polymeric structures maybe enhanced by grafting selected bioactive molecules to their surfaces and Appropriate cell coverage of the graft material may totally abrogate unwanted thrombo-inflammatory response. The end-point aim of this project is to develop tissue engineered synthetic arterial vessels from cells grown on functionalized nonwoven fiber structures made of PET or of an hybrid from PET and a bioresorbable polymer. This will require the development of PET or PET/resorbable polymer hybrid structures with mechanical compliance matching that of a small vascular artery; proper surface modification and functionalization capable of enhancing cell attachment and growth in order to generate hemocompatible, anti-thrombogenic and anti-inflammatory biomaterials. and finally the need that SMC/EC grown on the structures are resistant to pulsatile flow.Our ultimate goal is to bring this new nonwoven fiber grafts close to proof-of-concept for in vivo studies at the end of this project in order to translate the results of this research into clinical outcomes.