基于血管腔内重建技术的新型内皮祖细胞捕获脑血管覆膜支架的实验研究

Complicated cerebral aneurysm, such as giant, fusiform, dissecting and pseudo aneurysms, has always become a difficulty either for endovascular embolism or surgical clipping. Considering that the cerebral aneurysm is kind of arterial wall deficiency disease, endovascular treatment for isolation of the aneurysm sac is likely to overcome the insufficiency of coil embolism to achieve parent artery reconstruction and complete aneurysm occlusion. Despite that the balloon-expandable fully covered stent we invented has provide a new treatment option for complicated cerebral aneurysms in clinical with a satisfied total occlusion rate, however, in view of the deficiency of materials and stent design, it has limitations including unsatisfied flexibility, poor arterial wall adherence ability and low target lesion arrive rate. Moreover, the delayed endothelialization caused by coverage material is likely to cause in-stent thrombosis and stenosis. Consequently, we are trying to make an improvement from stent/membrane material, structure design, release manner, and the delivery system to enhance its flexibility and radio force to achieve better aneurysm neck occlusion and significant hemodynamic flow reverse in aneurysm sac to promote aneurysm healing, while the controlled releasing of CD34 antibody can capture endothelial progenitor cells to keep better patency of the parent artery. Furthermore, this stent is also supposed to be used in a rabbit aneurysm model to assess its feasibility, safety and efficacy in vivo.

颅内复杂性动脉瘤（巨大、梭形、夹层和假性动脉瘤）一直以来都是血管腔内治疗和外科手术夹闭的难题。鉴于脑动脉瘤是一种母体血管管壁缺陷性疾病，血管腔内隔绝技术有望克服目前瘤腔内栓塞技术的缺陷，达到重建载瘤血管，完全闭塞动脉瘤腔的治疗效果。本课题组研制的球扩式覆膜支架为难治性脑动脉瘤提供了新的治疗方法，然而，该覆膜支架尚存在支架整体顺应性差，在以迂曲为特点的母体动脉内贴壁不良、瘤口封堵不满意，以及靶病变到位率低的不足，外覆膜材造成内皮化延迟，增加了支架内血栓形成和再狭窄风险。本课题拟从支架骨架和膜材料选择、结构设计、释放方式、输送系统等方面着手，研发一种具有顺应性好、支撑力足，直接隔绝动脉瘤口，改变动脉瘤腔血流动力学，促进病变自行愈合，同时通过缓释CD34抗体捕获体循环内皮祖细胞以达到保持母体动脉长期通畅的新型脑血管专用覆膜支架，并通过植入治疗兔动脉瘤模型，评价其体内应用的可行性、安全性和有效性.

研究背景：脑动脉瘤破裂可引起极高的临床致残致死率。覆膜支架应用于脑动脉瘤治疗取得了良好疗效。然而，支架金属骨架体内植入后，复杂的血流动力学影响，加之膜性材料的阻隔、有造成内皮细胞的迁徙时间延长，内皮化延迟，血栓并发症发生率增加和管腔再狭窄等风险；镁合金体内植入后完全生物可降解，因此镁合金覆膜支架体内植入后短期内骨架完全生物降解后，可能有助于早期完成内皮化过程。血流动力学分析则有助于评估动脉瘤生长风险。.主要研究内容：在前期研究基础上，我们构建一种新型镁合金覆膜支架，支架骨架为可降解镁合金，膜材为ePTFE膜，输送系统为球囊导管。该支架具有体内完全可降解的优势。采用该支架系统体内植入治疗兔侧壁囊性动脉瘤模型，以评价其体内应用的可行性、安全性和有效性，并且与普通覆膜支架植入比较内皮化过程。入组一组前交通动脉瘤病例，根据大脑前动脉A1段发育对称、发育不良和缺如进行进一步分组，评估不同亚组的前交通动脉瘤血流动力学特点。.关键数据及其科学意义：1）完成了外科夹闭联合弹力蛋白酶孵化法制备兔右侧颈总动脉宽颈动脉瘤模型，该模型可用于血管内治疗装置（如弹簧圈和支架）体内植入的可靠性和安全性评估。2）普通覆膜支架体内植入治疗兔右侧颈总动脉宽颈动脉瘤模型，支架植入后具有满意的即刻和随访封堵效能，并且在6月左右完成内皮化过程。3）镁合金覆膜支架体内植入治疗兔右侧颈总动脉宽颈动脉瘤模型，具有和普通覆膜支架类似的即刻和随访封堵效能，并且随着镁合金支架骨架的体内降解，其内皮化完成要早于普通金属覆膜支架。4）通过血流动力学分析，比较不同A1段解剖结构下前交通动脉瘤的血流动力学特点，发现大脑前动脉A1段的直径差异和发育不对称情况与前交通血管管壁切应力（WSS）增加有关，而WSS升高可诱发前交通动脉瘤生长。上述研究结果可作为筛查脑动脉瘤破裂的高危人群的有效工具。