1. Drug-Eluting Bioresorbable Polymer Scaffolding for Treatment of Aortic Aneurys

1. 用于治疗主动脉瘤的药物洗脱生物可吸收聚合物支架

• 批准号: 8125695
• 负责人: Jack Cabell Griffis
• 金额: $ 35.64万
• 依托单位: MEDSHAPE SOLUTIONS, INC.
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-08-17 至 2013-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8125695
• 关键词: Abdomen; Abdominal Aortic Aneurysm; Accounting; Acute; Address; Admixture; Affect; Age; Anatomy; Aneurysm; Animal Model; Animals; Aorta; Aortic Aneurysm; Aortic Segment; Apoptosis; Biocompatible Materials; Biodegradation; Biological; Blood Vessels; Blood flow; Cardiovascular system; Cause of Death; Cessation of life; Characteristics; Chemistry; Chronic; Clinical; Complement Activation; Data; Development; Device or Instrument Development; Devices; Diagnosis; Doctor of Philosophy; Dose; Drug Delivery Systems; Drug Evaluation; Drug Formulations; Elderly; Evaluation; Evaluation Research; Family suidae; Funding; Healed; In Situ; In Vitro; Injectable; Lead; Light; Mechanics; Methods; Modeling; Operative Surgical Procedures; Patients; Performance; Pharmaceutical Preparations; Phase; Phototoxicity; Physiological; Pilot Projects; Polymer Chemistry; Polymers; Positioning Attribute; Postoperative Period; Process; Property; Radiologic Health; Research; Role; Running; Rupture; Ruptured Aortic Aneurysms; Safety; Screening procedure; Second Look Surgery; Series; Skin; Smooth Muscle; Solutions; Source; Surgeon; System; Techniques; Technology; Testing; Therapeutic; Therapeutic Agents; Time; Tissues; Toxic effect; Treatment Efficacy; Tunica Adventitia; United States; United States Food and Drug Administration; Universities; Validation; Visible Radiation; Weight-Bearing state; animal efficacy; biodegradable polymer; biomaterial compatibility; clinically relevant; cytotoxicity; design; dosage; experience; genotoxicity; healing; in vivo; innovation; instrument; instrumentation; irritation; meetings; minimally invasive; mouse model; novel; polymerization; pressure; prevent; professor; prototype; repaired; scaffold; success

DESCRIPTION (provided by applicant): This proposal is focused on the development of a bioabsorbable polymeric scaffold intended to provide both time-release delivery of therapeutic agents as well as structural support in the treatment of aortic aneurysms. An abdominal aortic aneurysm (AAA) is a condition in which the aorta, the main blood vessel in the abdomen, expands like a balloon. The aneurysm weakens the wall of the aorta and can result in rupture. Because the volume of blood flowing through the aorta is under relatively high pressure, a rupture can be catastrophic, resulting in death. Up to 75% of patients are asymptomatic prior rupture. In the United States, approximately one in every 250 people over the age of 50 will die of a ruptured aortic aneurysm. Aortic aneurysms affect as many as eight percent of people over the age of 65 and remains the 13th leading cause of death in the United States, accounting for more than 15,000 deaths each year. Research has shown that in the setting of AAA formation, the smooth muscle component of the arterial wall undergoes apoptosis and ceases to be mechanically relevant. The adventitia becomes thickened and assumes the role as the major load bearing component of the vessel wall. Overall, these results have lead us to suggest that since the adventitia is the vulnerable component of the arterial wall in advanced AAA, that an "outside-in" therapy to mechanically and biologically stabilize the vessel wall may represent a more efficacious approach to aneurysm repair than those currently offered. MedShape Solutions has developed a series of bioabsorbable polymers capable of carrying various therapeutic agents. The proposed bioabsorbable polymeric scaffold will be developed to provide for the delivery of an agent to treat the aneurysmal tissue as well as provide structural support for the diseased portion of the aorta to prevent further expansion and/or rupture. In addition, the polymer chemistries under development are capable of in-situ polymerization which would allow the placement of the scaffold around aortic segments that would normally be classified as having unfavorable anatomy and that might go untreated otherwise. Finally, the delivery system to be developed will be compatible with laparoscopic techniques which would make it significantly less invasive than surgical repair. The aims of the Phase II proposal are to fundamentally investigate the polymeric scaffolding chemistry as it relates to mechanical characteristics as well as biodegradation and drug elution. In addition, the prototype delivery system for the drug/device combination will be finalized and evaluated in vivo in a 12 week large animal efficacy study. The primary research team will consist of Jack Griffis (PI), who is an expert in cardiovascular device development; Ken Gall PhD, a professor from Georgia Tech who specializes in polymers; and W. Robert Taylor, MD, a cardiologist from Emory University that specializes in AAA, as well as two other prominent vascular and cardiothoracic surgeons that will provide input into the surgical approach. PUBLIC HEALTH RELEVANCE: Abdominal aortic aneurysms (AAA) affect as many as eight percent of people over the age of 65 and remains the 13th leading cause of death in the United States, accounting for more than 14,000 deaths each year. In addition, for those who receive treatment, surgical revision rates are as high as 26% and up to 50% of those diagnosed are not eligible for the latest, minimally invasive techniques. This project will provide an approach that is both compatible with minimally invasive techniques as well as provide a means to reduce post-operative complications while delivering therapeutic agents directly into the aneurysmal tissue.

描述（由申请人提供）：该提案的重点是开发生物可吸收聚合物支架，旨在提供治疗剂的缓释递送以及主动脉瘤治疗中的结构支撑。腹主动脉瘤 (AAA) 是指主动脉（腹部的主要血管）像气球一样扩张的病症。动脉瘤会削弱主动脉壁并可能导致破裂。由于流经主动脉的血量处于相对较高的压力下，因此破裂可能是灾难性的，导致死亡。高达 75% 的患者破裂前没有症状。在美国，50 岁以上的人中，大约每 250 人中就有 1 人死于主动脉瘤破裂。主动脉瘤影响多达 8% 的 65 岁以上老年人，并且仍然是美国第 13 大死因，每年导致超过 15,000 人死亡。 研究表明，在 AAA 形成的情况下，动脉壁的平滑肌成分会发生细胞凋亡，并不再具有机械相关性。外膜变厚并承担血管壁主要承重部件的作用。总体而言，这些结果使我们认为，由于外膜是晚期 AAA 中动脉壁的脆弱部分，因此从机械和生物角度稳定血管壁的“由外向内”疗法可能代表一种更有效的动脉瘤修复方法比目前提供的那些。 MedShape Solutions 开发了一系列能够携带各种治疗剂的生物可吸收聚合物。所提出的生物可吸收聚合物支架将被开发用于提供治疗动脉瘤组织的药剂的递送以及为主动脉的患病部分提供结构支撑以防止进一步扩张和/或破裂。此外，正在开发的聚合物化学能够进行原位聚合，这将允许将支架放置在通常被归类为具有不利解剖结构并且可能未经处理的主动脉节段周围。最后，待开发的输送系统将与腹腔镜技术兼容，这将使其侵入性明显低于手术修复。 第二阶段提案的目的是从根本上研究聚合物支架化学，因为它与机械特性以及生物降解和药物洗脱有关。此外，药物/设备组合的原型输送系统将在为期 12 周的大型动物功效研究中最终确定并进行体内评估。主要研究团队将由心血管设备开发专家Jack Griffis（PI）组成； Ken Gall 博士，佐治亚理工学院教授，​​专门研究聚合物；埃默里大学心脏病专家 W. Robert Taylor 医学博士（专门研究 AAA）以及另外两位著名的血管和心胸外科医生将为手术方法提供意见。 公共健康相关性：腹主动脉瘤 (AAA) 影响着 8% 的 65 岁以上老年人，并且仍然是美国第 13 大死因，每年导致超过 14,000 人死亡。此外，对于接受治疗的患者来说，手术翻修率高达 26%，并且高达 50% 的确诊患者不符合最新微创技术的条件。该项目将提供一种既与微创技术兼容的方法，又提供一种减少术后并发症的方法，同时将治疗剂直接输送到动脉瘤组织中。