新型填充式移植物治疗升主动脉瘤的实验研究

Ascending aortic aneurysm is one of the extremely dangerous cardiovascular diseases, for which the minimally invasive treatment needs to be developed urgently. We have successfully provided endovascular repair for a number of patients with ascending aortic pathology using tube-shaped stent graft, which has been published in the Journal of American Cardiovascular College. However, a high percentage of patients are still deemed unfit for endovascular procedure in clinical practice. The main problem is that the short and curved ascending aorta often fails to provide sufficient landing zone for the endovascular graft. .How to solve it? We propose a new design of sac-filling graft which is surrounded by a fillable endobag. The endobag can be filled with an in situ curing polymer. Once the polymer-containing endobags fill the aneurysm sac, the stent graft can be anchored within the aneurysm sac to achieve positional stability. At the same time, the filled endobag eliminate the aneurysm sac and consequently eliminate the potential space for blood flow in the aneurysm (endoleak). It can overcome the insufficiency of landing zone in the ascending aorta, avoid covering the important branch vessels, and reduce the occurrence of adverse events such as endoleak. .In the preliminary studies, we have developed the super compliant stent, semi compliant outer balloon and double component filling agent. On this basis, we would conduct the following researches:.1)First, we plan to develop the filling-function components, transporting-function components and releasing control components to establish a new type of ascending aortic filing grafts system..2)Second, on an in vitro model, we plan to verify the feasibility of the sac-filling graft system in the treatment of ascending aortic aneurysm by evaluating the delivery, location, release, filling and retracting process of the graft, and by determine the sealing performance of the filling path and anchoring force from the attached endobag. Based on the experimental results, we would further improve the design of the stent graft system and to explore the best way to release the stent graft..3)Third, on the animal model, we plan to evaluate the safety and effectiveness of the filling graft system by analyzing the technical success rate, complication and mortality during perioperative and following period. And we would study the characteristics and rules of the vascular remodeling after application of the stent graft in the ascending aorta by investigating the change of the diameter of ascending aorta, the pathological changes of the aortic wall and aneurysm, and the biomechanical properties of vascular wall..This study might provide important scientific data and new technology for the treatment of critical ascending aortic aneurysm.

升主动脉瘤病情凶险，微创治疗问题亟待解决。我们采用直管型移植物成功微创治疗升主动脉病变并发表在JACC上，但实践中又发现仍有较高比例患者无法获益，主要问题在于短而弯的升主动脉常常不能为腔内移植物提供足够锚定区。如何解决呢？我们提出新型填充式移植物设计，利用外附球囊填充后与瘤腔形成的作用力强化锚定，既克服升主动脉锚定区不足，又避免遮蔽重要分支血管，并能减少内漏等不良事件发生。在预研究明确超柔顺支架主体、半顺应性外附球囊和双组份填充剂基础上，本项目拟：1)研制填充、输送及释放控制组件，构建新型升主动脉填充式移植物系统；2）在体外模拟模型上，研究填充式移植物系统治疗升主动脉瘤的可行性，并反馈改进设计，探索释放的最佳方法；3）在动物模型上，评价填充式移植物系统的安全性和有效性，研究其应用后升主动脉血管重构的特征和规律。本研究所获结果将可能为危重升主动脉瘤的治疗提供重要的科学数据和全新的技术方案。

1.研究背景：.升主动脉瘤病情凶险，微创治疗问题亟待解决。我们采用直管型移植物成功微创治疗升主动脉病变并发表在JACC上，但实践中又发现仍有较高比例患者无法获益，主要问题在于短而弯的升主动脉常常不能为腔内移植物提供足够锚定区。如何解决呢？我们提出新型填充式移植物设计，利用外附球囊填充后与瘤腔形成的作用力强化锚定，既克服升主动脉锚定区不足，又避免遮蔽重要分支血管，并能减少内漏等不良事件发生。.2.主要研究结果：.本项目完成了1)升主动脉瘤形态学特征数据的收集整理与统计分析，为研制适用人体解剖结构的填充型移植物系统提供参考。进一步采用镍钛合金丝、ePTFE、涤纶膜和聚氨酯薄膜为材料成功制作获得填充型移植物样品，改进制作了集成相关功能组件的配套输送系统，并研发获得粘度、固化时间和力学性能达标的新型双组份加成型液体硅橡胶作为填充剂，形成了结构功能较为完整的填充型移植物系统；2）通过在升主动脉瘤体外模型上开展体外实验研究，初步证明填充型移植物系统的可行性。该系统导入、定位、释放、填充和撤出等步骤均可顺利完成；移植物位置形态良好，扩张完全，外附球囊可充满瘤腔，不遮盖冠脉开口和弓上分支动脉开口，为移植物提供足够的锚定力；3）研究成功探索了一种构建远近端锚定区不足的升主动瘤动物模型的建模方法，初步观察该动物模型长期稳定可控；4）在动物模型上，初步验证该移植物系统治疗远近端锚定区不足的升主动脉瘤是安全有效的。.3.科学意义：.本研究所获结果将可能为危重升主动脉瘤的治疗提供重要的科学数据和新的技术方案。