A Nanofibrous Bioactive Prosthetic Sewing Cuff

描述（由申请人提供）：当自体瓣膜退行性疾病或细菌感染进展导致瓣膜功能障碍，从而影响心输出量时，适用于使用人工瓣膜进行心脏瓣膜置换术。据估计，美国每年植入50，000个人工瓣膜，由于人口老龄化以及在较小程度上更积极的二尖瓣关闭不全方法，这一数字正在增加。细菌感染（人工瓣膜心内膜炎或PVE）和血栓形成/血栓栓塞是与这些瓣膜植入相关的主要并发症。该I期STTR资助的目标是在体外开发一种新型纳米纤维聚酯袖带，该袖带将通过在较长时间内释放选定的药物同时提供局部抗感染和抗血栓形成特性。我们的假设是，生物活性剂可以被纳入本体聚合物溶液，然后通过专有的静电纺丝技术的纳米纤维材料的合成。然后，这些试剂可以在暴露于生理条件时以缓慢、持续的方式从相应的nPET材料中同时释放，同时保持生物活性。我们的初步数据支持这一假设。这项研究的具体目标是：1）优化合成纳米纤维聚酯袖带的方法（nPET袖带），2）将选定的抗菌剂和抗凝血酶剂掺入nPET袖带结构中（生物活性nPET袖带），3）表征新型生物活性nPET材料的物理性质，4）使用特定测定法在静态和洗涤条件下评估药物随时间从生物活性nPET袖带的洗脱曲线，5）使用特定的生物学测定来检查静态和洗涤的生物活性nPET袖带的体外生物学特性，以及6）使用兔背侧皮下植入模型来评价对照和生物活性nPET袖带的体内抗感染性。目前的预测表明，在未来十年内将植入更多数量的人工机械瓣膜，保守估计每年有50，000个瓣膜。仅PVE的相关医疗保健成本预计为每位患者50，000美元，预计年市场超过2500万至7500万美元。该技术还可应用于新型纳米纤维装置，例如血管移植物、颈动脉补片材料、导管套囊、伤口敷料和缝合材料。在该项目的第II阶段，将使用高流量动脉模型在体内评价该新技术，该模型用于评价先前的套囊生物材料的抗感染性。公共卫生相关性：当自体瓣膜退行性疾病或细菌感染进展导致瓣膜功能障碍，从而影响心输出量时，适用于使用人工瓣膜进行心脏瓣膜置换术。细菌感染（人工瓣膜心内膜炎或PVE）和血栓形成/血栓栓塞是与这些瓣膜植入相关的主要并发症。该I期STTR资助的目标是在体外开发一种新型纳米纤维聚酯袖带，该袖带将通过在较长时间内释放选定的药物同时提供局部抗感染和抗血栓形成特性。目前的预测表明，在未来十年内将植入更多数量的人工机械瓣膜，保守估计每年有50，000个瓣膜。仅PVE的相关医疗保健成本预计为每位患者50，000美元，预计年市场超过2500万至7500万美元。

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.