Totally Bioresorbable Drug-eluting Peripheral Polymer Stents

描述（由申请人提供）：本项目旨在证明使用我们新开发的新型快速支架制造（RSF）系统制造具有适当机械性能的生物可吸收药物洗脱聚（l-丙交酯）（PLLA）支架是可行的。这种新型系统是基于计算机辅助设计（CAD）的，并且具有通过使用聚合物颗粒和粉末直接生产生物可吸收聚合物支架的能力，而没有任何中间步骤，例如制造聚合物管和纤维。这将大大减少生物可吸收支架制造过程的处理时间和成本。 在本项目中，我们将首先在RSF中优化PLLA支架制造参数。将制造具有单螺旋和双螺旋图案的支架并测试其机械性能。常用的抗炎和抗增殖药物雷帕霉素（西罗莫司）和无定形生物可吸收聚合物聚D，L-丙交酯将在本I期可行性研究中用作药物/聚合物涂层。将测试机械性能，如预置和径向刚度、急性回缩、纵向短缩。将使用伽马辐射或电子束辐射对制造的药物洗脱支架进行灭菌，并将研究体外药物洗脱曲线。这些支架的生物降解行为也将在体外进行表征。 在完成该I期研究后，我们计划与主要支架制造商（如Abbott Vascular）合作开展II期动物研究。 公共卫生相关性：生物可吸收聚合物支架是下一代支架开发的重点。由于生物可吸收支架所能提供的所有益处，它可能成为外周动脉疾病的新护理标准。由于目前市场上还没有FDA批准的生物可吸收支架，因此对支架和新制造技术的需求更强烈，这些技术可以提高支架生产效率并减少支架开发时间和成本。 使用我们新开发的快速支架制造（RSF）系统，该项目将证明制造药物洗脱生物可吸收聚（L-丙交酯）（PLLA）支架的可行性，该支架具有适当的机械性能和30天内释放约80%药物的药物洗脱曲线。这种新型系统能够通过使用聚合物颗粒和粉末直接生产生物可吸收聚合物支架，而无需中间步骤，例如制造聚合物管和纤维。常用的抗炎和抗增殖药物雷帕霉素（西罗莫司）和无定形生物可吸收聚D，L-丙交酯将在本I期可行性研究中用作药物/聚合物涂层。

DESCRIPTION (provided by applicant): The objective of the project is to demonstrate that it is feasible to fabricate a bioresorbable drug eluting poly (l-lactide) (PLLA) stent with appropriate mechanical properties using our newly developed novel rapid stent fabrication (RSF) system. This novel system is Computer Aided Design (CAD) based and has the capability to directly produce bioresorbable polymer stents by using polymer pellets and powders without any intermediate steps, such as making of polymer tubes and fibers. This will drastically reduce the processing time and the cost of the bioresorbable stent fabrication process. In this project, we will first optimize PLLA stent fabrication parameters in our RSF. Stents with single and double helical patterns will be fabricated and tested for their mechanical properties. The commonly used anti-inflammatory and anti-proliferative drug, rapamycin (sirolimus), and amorphous bioabsorbable polymer, poly-D,L-lactide, will be applied as drug/polymer coating in this phase I feasibility study. Mechanical properties, such as crimping and radial stiffness, acute recoil, foreshortening, will be tested. Fabricated drug elution stents will be sterilized using gamma-radiation or e-beam radiation and there in vitro drug elution profiles will be studied. The biodegradation behavior of these stents will also be characterized in vitro. Upon completion of this Phase I study, we plan to move forward by conducting a Phase II animal study in collaboration with a major stent manufacturer, such as Abbott Vascular. PUBLIC HEALTH RELEVANCE: Bioresorbable polymer stents are the focus of the next generation stent development. With all the benefits they can offer, bioresorbable stents may become a new standard of care in peripheral artery disease. Since currently there is no FDA approved bioresorbable stents on the market yet, there is a stronger demand for both stents and new fabrication technologies that can increase stent production efficiency and reduce stent development time and cost. Using our newly developed rapid stent fabrication (RSF) system, this project will demonstrate the feasibility of fabricating drug eluting bioresorbable poly(L-lactide) (PLLA) stents with appropriate mechanical properties and a drug-eluting profile of approximately 80% drug being released in 30 days. This novel system has the capability to directly produce bioabsorbable polymer stents by using polymer pellets and powders without intermediate steps, such as the making of polymer tubes and fibers. The commonly used anti-inflammatory and anti-proliferative drug, rapamycin (sirolimus), and amorphous bioasorbable poly-D,L-lactide will be applied as drug/polymer coating in this phase I feasibility study.