Biodegradable Elastomers and Resorbable Synthetic Vascular Grafts

可生物降解的弹性体和可吸收的合成血管移植物

• 批准号: 10580321
• 负责人: Xiaochu Ding
• 金额: $ 46.95万
• 依托单位: MICHIGAN TECHNOLOGICAL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-03-15 至 2026-02-28
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10580321
• 关键词: Adhesions; Alkynes; Animal Model; Animals; Arteries; Autologous; Autologous Transplantation; Blood Platelets; Bypass; Cause of Death; Cell Culture Techniques; Cells; Chemistry; Clinical; Coronary Artery Bypass; Data; Data Analyses; Deposition; Diameter; Disease; Elasticity; Elastomers; Electrospinning; Endothelium; Engineering; Evaluation; Extracellular Matrix; Female; Fiber; Future; Glycerol; Heparin; Immobilization; Immune response; Implant; In Situ; In Vitro; Infiltration; Legal patent; Length; Modeling; Modulus; Molecular Weight; Morphology; Natural regeneration; Outcome; Patients; Performance; Peripheral; Polyesters; Polymers; Porosity; Positron-Emission Tomography; Proliferating; Property; Rattus; Regenerative capacity; Research; Resources; Stains; Stenosis; Structure; Sulfhydryl Compounds; Surface; Surgical sutures; Techniques; Temperature; Tensile Strength; Thick; Thrombosis; Tissues; Training; Tunica Adventitia; Underrepresented Students; Vascular Graft; abdominal aorta; absorption; biodegradable polymer; biomaterial compatibility; caprolactone; crosslink; crystallinity; design; elastomeric; fabrication; hydrophilicity; male; mechanical properties; monomer; pediatric patients; recruit; scaffold; sebacic acid; serinol; standard care; thrombotic; translational study; undergraduate student

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.

项目摘要 动脉闭塞疾病是世界范围内主要的死亡原因。只有在美国，有 每年约有40万例冠状动脉搭桥术和46万例外周动脉搭桥术。 自体移植是治疗的黄金标准。然而，这些患者中约有三分之一无法服用这种药物 治疗，因为有限的自体资源。不可降解的接枝(例如，PET和ePTFE)已经被 多年来作为自体移植物的替代品，但由于血栓形成，它们在小动脉(&lt；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出用于原位动脉。 利用宿主的再生能力进行再生。不能降解的移植物发生并发症 可以最小化。然而，目前存在的可生物降解聚合物中没有一种在临床上产生 有用的可吸收移植物。 在这项建议中，我们试图合成新的可生物降解的功能性聚酯弹性体，并用于 设计完全可吸收的合成移植物，具有可调的降解、机械性能和亲水性。 我们预计完全改建的移植物可以与天然动脉一起生长，这对 儿科病人。这项提议有三个主要目标。目标1：设计、合成和 用内源性和生物相容性表征可生物降解功能性聚酯弹性体 单体。目标2：设计具有可调节降解和机械性能的抗血栓纤维移植物 属性。目的：评价大鼠腹主动脉间置原位移植模型中的候选移植物 动脉再生。该项目的数据将被用于大型动物研究的移植物参数优化。 在未来，鉴于大型动物的降解速度较快，再生能力较慢。本科生 包括代表性不足的学生在内的学生将被招募并接受培训，以进行该项目的研究， 例如材料合成和表征、嫁接制造和表征、细胞培养研究以及 组织切片、染色和数据分析等。