Biodegradable Elastomers and Resorbable Synthetic Vascular Grafts

项目摘要 闭塞性动脉疾病是全世界死亡的主要原因。只有在美国，有 每年进行约400，000例冠状动脉旁路手术和460，000例外周动脉旁路手术。 自体移植是金标准治疗。然而，这些患者中约有1/3无法服用这种药物。 由于自身资源有限，不可降解的移植物（例如，PET和ePTFE）已被 多年来一直是自体移植物的替代品，但由于血栓形成，它们在小动脉（< 6 mm）中表现不佳， 狭窄，通畅率低。另一方面，生物可吸收移植物已被提议用于原位动脉 利用宿主的再生能力进行再生。并发症发生在不可降解的移植物中 可以最小化。然而，目前存在的可生物降解的聚合物中没有一种产生临床上可生物降解的聚合物。 有用的可吸收移植物。 在本提案中，我们寻求合成新的可生物降解的功能性聚酯弹性体，并用于 设计具有可调降解性、机械性能和亲水性的完全可吸收的合成移植物。 我们希望完全重塑的移植物可以沿着天然动脉生长，这对于 儿科患者。这项建议有三个主要目标。目标1：设计、合成和 使用内源性和生物相容性的生物可降解功能聚酯弹性体的表征 单体。目的2：设计具有可调降解和机械性能的抗血栓纤维移植物 特性.目的3：评价大鼠腹主动脉间置模型中的候选移植物，用于原位 动脉再生该项目的数据将用于优化大型动物研究的移植参数 在未来，考虑到大型动物的降解速度更快，再生能力更慢。本科 将招募和培训学生，包括代表性不足的学生，在这个项目中进行研究， 例如材料合成和表征、移植物制造和表征、细胞培养研究，以及 组织切片、染色和数据分析等。

Project Summary Occlusive artery diseases are a leading cause of death worldwide. Only in the U.S., there are approximately 400,000 coronary artery bypasses and 460,000 peripheral artery bypasses performed each year. Autografts are the gold-standard treatment. However, approximately 1/3 of these patients are unable to take this treatment because of limited autologous resources. Nondegradable grafts (e.g., PET and ePTFE) have been alternative to the autografts over the years, but they perform poorly in small arteries (< 6 mm) due to thrombosis, stenosis, and low patency rate. On the other hand, bioresorbable grafts have been proposed for in situ arterial regeneration using the host regenerative capacities. The complications occurred in the nondegradable grafts can be minimized. However, none of the currently existing biodegradable polymers have produced a clinically useful resorbable graft. In this proposal, we seek to synthesize new biodegradable functional polyester elastomers and use to engineer fully resorbable synthetic grafts with tunable degradation, mechanical properties, and hydrophilicity. We expect the fully remodeled grafts can grow along with native arteries, which is particularly important for pediatric patients. There are three main objectives in this proposal. Objective 1: Design, synthesis and characterization of the biodegradable functional polyester elastomers using endogenous and biocompatible monomers. Objective 2: Engineer anti-thrombotic fibrous grafts with tunable degradation and mechanical properties. Objective 3: Evaluation of candidate grafts in rat abdominal aorta interposition models for in situ arterial regeneration. Data from this project will be used to optimize the graft parameters for large animal studies in the future, given a quicker degradation and slower regenerative capacities in large animals. Undergraduate students including underrepresented students will be recruited and trained to conduct research in this project, such as material synthesis and characterizations, graft fabrication and characterizations, cell culture studies, and tissue section, staining and data analyses, among others.