The central objective of this research project is to improve the biological characteristics of endovascular prostheses. Slightly less than 3 years ago, the investigators initiated a multidisciplinary program to fabricate and evaluate, in suitable animal models, biodegradable polymer stents. The objectives were to improve the engineering of these devices to enhance their intrinsic biocompatibility, to develop methods to control porosity and hydration capacity to permit these devices to function as vehicles for drug delivery, and to investigate the use of these devices for local delivery of viral vectors carrying genes intended to favorably alter the biology of the instrument vessel. In the initial funding period, they have made a number of improvements in design and fabrication, developed techniques for transluminal deployment, and evaluated several generations of devices for their mechanical properties, delivery capacity and biocompatibility following implantation into porcine iliac arteries. They have, in parallel, evaluated the effects of overexpression of several candidate genes. On the basis of their experience, they have produced stents of 3 designs, and predicated on the characteristics of these designs, envision 3 alternative approaches to achieving our general goal of a """"""""genetically enhanced"""""""" vascular stent. The objectives for the next funding period are i) to compare these three designs and their corresponding approaches for clinically relevant endpoints in a porcine iliac angioplasty model, and ii) based on the most promising approach(es), evaluate local overexpression of 3 specific genes, VEGF, COX-1 and an antisense p62cdc6 mRNA for effects on reendothelialization, thrombosis and neointima formation, respectively. While the clinical results obtained with current metallic vascular stents have improved, important limitations and concerns regarding widespread use of permanent metal endovascular prostheses remain. Development of biocompatible, biodegradable vascular prostheses and approaches to enhance the performance of such devices through local gene transfer remain goals with potentially important clinical impact.
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