? Coronary arteries on the heart often buildup plaque that narrows the pathway of the artery which inhibits blood flow. Coronary artery disease accounts for the greatest mortality in the USA (1 in 5 deaths). This disease is frequently treated with stents, implantable metal mesh tubes that enlarge the vessel for blood to flow. A significant unmet need in the treatment of coronary artery disease is the lack of an X-ray visible, resorbable stent that can serve as a drug-delivery vehicle for the prevention of re-narrowing as well as a temporary mechanical support to keep the vessel open until healing stabilizes. Stent resorption at this point would allow the maximum patient benefit of natural vascular reconstruction. A resorbable stent would also eliminate patient re-treatment complications associated with metal stents. Metal stent designs require materials that can undergo significant shape alterations when expanded in order to enlarge the vessel. REVA has eliminated this problem with their patented """"""""slide and lock"""""""" stent design. REVA has shown that stents in this design can function in an in vivo artery model even when fabricated from resorbable poly(DTE carbonate), invented by the co-investigator Professor Kohn. The objectives of this Phase 1 grant are to: (i) demonstrate the feasibility of fabricating X-ray visible (""""""""iodinated""""""""), resorbable stents using new polycarbonates and REVA's proprietary slide-and-lock stent design, and (ii) show that these stents meet defined bench and in vivo performance criteria for x-ray visualization, mechanical stent function and vascular biocompatibility.
Three specific aims are proposed:
(AIM 1) synthesis of a family of X-ray visible polymers based on the chemical modification of an existing, resorbable polymer, poly(DTE carbonate) through scaleable iodination and/or polymerization methods;
(AIM 2) testing of iodinated polymers and fabrication of stent prototypes to meet necessary clinical criteria for radial strength, deployment and X-ray visibility; and, (AIM 3) biological testing of iodinated polymers to assess blood cell and protein interactions, toxicity and, most importantly, an in vivo evaluation of radio-opaque resorbable stent prototypes in a predictive animal model. Upon successful completion of Phase 1, this work will converge in Phase II with REVA's separate drug delivery program and advance toward commercial products. A resorbable stent represents a major commercial opportunity. ? ?
| Weber, Norbert; Pesnell, Aaron; Bolikal, Durgadas et al. (2007) Viscoelastic properties of fibrinogen adsorbed to the surface of biomaterials used in blood-contacting medical devices. Langmuir 23:3298-304 |
