Application of a rabbit-elastase aneurysm model for preliminary histology assessment of the PPODA-QT liquid embolic.
Application of a rabbit-elastase aneurysm model for preliminary histology assessment of the PPODA-QT liquid embolic.
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DOI：
10.25259/sni_163_2021
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发表时间：
2021
影响因子：
--
通讯作者：
Becker TA
中科院分区：
文献类型：
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作者：
Huckleberry A;Merritt W;Cotter T;Settanni C;Preul MC;Ducruet AF;Becker TA
PPODA-QT 是一种正在开发的新型液体栓塞药物，用于治疗脑动脉瘤。我们试图测试兔弹性蛋白酶动脉瘤模型，以评估 PPODA-QT 栓塞后的组织反应。在十四只新西兰白兔身上制作了实验性弹性蛋白酶诱导的动脉瘤。八只动物用于动脉瘤模型和血管内栓塞技术开发。六只接受 PPODA-QT 治疗的动物参加了该研究。在急性（n = 2）、1个月（n = 2）和3个月（n = 2）时间点收获对照和动脉瘤组织，并准备组织用于组织学评估。所有 14 个兔弹性蛋白酶动脉瘤均导致中小型动脉瘤高度（<10 毫米圆顶高度），具有高度可变的颈部形态、小中线圆顶直径和超宽的圆顶与颈部 (d: n) 比率。对用 PPODA-QT 治疗的四个动脉瘤进行的组织学评估表明，动脉瘤壁弹性蛋白重组为平滑肌层，并且早在 1 个月生存时间点即可观察到。在动脉瘤颈处，PPODA-QT 界面处形成均匀的新内膜层 (200-300 μm)，将载瘤血管与动脉瘤穹顶密封。在 1 个月和 3 个月的生存时间点没有明显的不良免疫反应。 PPODA-QT 成功栓塞治疗后的动脉瘤。 PPODA-QT 栓塞后，观察到新内膜组织生长和重塑，免疫反应极小。在兔子身上制作的实验性动脉瘤均很小，颈部形态不一致。 PPODA-QT 的进一步测试将在更大的动脉瘤模型中进行，以便在人体临床研究之前优化设备输送和动脉瘤愈合评估。
PPODA-QT is a novel liquid embolic under development for the treatment of cerebral aneurysms. We sought to test the rabbit-elastase aneurysm model to evaluate the tissue response following PPODA-QT embolization. Experimental elastase-induced aneurysms were created in fourteen New Zealand White Rabbits. Eight animals were used for aneurysm model and endovascular embolization technique development. Six PPODA-QT-treated animals were enrolled in the study. Control and aneurysm tissues were harvested at acute (n = 2), 1-month (n = 2), and 3-month (n = 2) timepoints and the tissues were prepared for histology assessment. All fourteen rabbit-elastase aneurysms resulted in small and medium aneurysm heights (<10 mm dome height) with highly variable neck morphologies, small midline dome diameters, and beyond-wide dome-to-neck (d: n) ratios. Histological evaluation of four aneurysms, treated with PPODA-QT, demonstrated reorganization of aneurysm wall elastin into a smooth muscle layer, and observed as early as the 1-month survival timepoint. At the aneurysm neck, a homogenous neointimal layer (200–300 μm) formed at the PPODA-QT interface, sealing off the parent vessel from the aneurysm dome. No adverse immune response was evident at 1- and 3-month survival timepoints. PPODA-QT successfully embolized the treated aneurysms. Following PPODA-QT embolization, neointimal tissue growth and remodeling were noted with minimal immunological response. The experimental aneurysms created in rabbits were uniformly small with inconsistent neck morphology. Further testing of PPODA-QT will be conducted in larger aneurysm models for device delivery optimization and aneurysm healing assessment before human clinical investigation.