| The use of autologous blood vessels for bypassing occluded small-diameter vessels is routine procedure. However, it is estimated that in 25–30% of clinical cases, an autologous graft is not adequate or available. Small-diameter synthetic vascular grafts, in their present design, are not fulfilling the requirement of acceptable long-term patency rate, and consequently are not clinically used. This difficulty in maintaining the patency of small-diameter vascular grafts is associated with an unfavorable host response in which vascular cells from the surrounding blood conduits migrate into the synthetic graft at the anastomoses, and proliferate. This leads to the occlusion of the graft, resulting in failure of the procedure.; One approach in solving this patency problem consists in transforming the current design into a bioactive graft that would stimulate a favorable host reaction. This could be achieved by creating a “hybrid vascular graft” that would serve as a support for a drug delivery system aimed at locally releasing pharmacologically active components to control cell migration and proliferation. In this study, two different classes of polymers having adequate physical properties were evaluated as drug delivery vehicles: an absorbable polyester-based gel former, and degradable polysaccharide-based hydrogels and solutions. The research program consisted in four major steps. First, synthesizing the polymeric carriers and assessing their cytocompatibility using in vitro cell culture assays. Second, impregnating the carriers into the internodal space of ePTFE vascular grafts and evaluating the in vivo general biocompatibility of the modified ePTFE using a rat model. Third, determining the hemocompatibility of modified grafts by the use of an ex vivo shunt created in rabbits, and also by using an in vivo canine model for select graft treatments. Fourth, releasing a select therapy (aanti-migratory RGD peptide) from the polymeric matrices and evaluating its effect on the biological responses.; Overall, this experimental program allowed determining that modifying ePTFE vascular grafts by using its microstructure to incorporate a drug release system improved the chances for this type of graft to be clinically successfully used as bypass for small-diameter blood vessels in the future. |
