A Nanofibrous Bioactive Prosthetic Sewing Cuff

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DESCRIPTION (provided by applicant): Cardiac valve replacement using prosthetic valves is indicated when progression of degenerative disease or bacterial infection of the native valve results in valvular dysfunction, thereby impacting on cardiac output. An estimated 50,000 prosthetic valves are implanted annually in the United States, with this number increasing due to an aging population and, to a lesser extent, a more aggressive approach to mitral valve insufficiency. Bacterial infection (prosthetic valve endocarditis or PVE) and thrombosis/thromboembolisms are major complications associated with implantation of these valves. The goal of this Phase I STTR grant is to develop in vitro a novel nanofibrous polyester cuff that will simultaneously provide localized infection-resistance and antithrombotic properties via release of selected agents over an extended period of time. Our hypothesis is that biologically-active agents can be incorporated into the bulk polymer solution followed by synthesis of the nanofibrous material via proprietary electrospinning technology. These agents can then be simultaneously released from the respective nPET materials in a slow, sustained fashion upon exposure to physiological conditions while maintaining biologic activity. Our preliminary data supports this hypothesis. The specific objectives of this study are to: 1) optimize methodology for synthesizing nanofibrous polyester cuffs (nPET cuffs), 2) incorporate selected antimicrobial and antithrombin agents into the nPET cuff constructs (bioactive nPET cuffs), 3) characterize physical properties of novel bioactive nPET materials, 4) assess drug elution profiles from bioactive nPET cuffs over time under static and washing conditions using specific assays, 5) examine in vitro biological properties of static and washed bioactive nPET cuffs using specific biologic assays and 6) evaluate control and bioactive nPET cuffs for in vivo infection-resistance using a rabbit dorsal subcutaneous implantation model. Current projections indicate that a greater number of prosthetic mechanical valves will be implanted over the next ten years, with conservative estimates of 50,000 valves per year. The associated health care costs from PVE alone are projected to be $50,000 per patient with a projected annual market in excess of $25-75 million. This technology can also be applied to novel nanofibrous devices such vascular grafts, carotid patch material, catheter cuffs, wound dressings and suture material. In Phase II of this project, this novel technology will be evaluated in vivo using a high flow arterial model employed to evaluate previous cuff biomaterials for infection-resistance. PUBLIC HEALTH RELEVANCE: Cardiac valve replacement using prosthetic valves is indicated when progression of degenerative disease or bacterial infection of the native valve results in valvular dysfunction, thereby impacting on cardiac output. Bacterial infection (prosthetic valve endocarditis or PVE) and thrombosis/thromboembolisms are major complications associated with implantation of these valves. The goal of this Phase I STTR grant is to develop in vitro a novel nanofibrous polyester cuff that will simultaneously provide localized infection-resistance and antithrombotic properties via release of selected agents over an extended period of time. Current projections indicate that a greater number of prosthetic mechanical valves will be implanted over the next ten years, with conservative estimates of 50,000 valves per year. The associated health care costs from PVE alone are projected to be $50,000 per patient with a projected annual market in excess of $25-75 million.