Department of Biomedical Engineering, University of Utah, Salt Lake City, UT, USA; Utah Center for Nanomedicine, University of Utah, Salt Lake City, UT, USA.
TheraTarget, Inc., Salt Lake City, UT, USA.
Acta Biomater. 2022 Oct 1;151:174-182. doi: 10.1016/j.actbio.2022.08.003. Epub 2022 Aug 8.
Cerebral aneurysms (CA), an abnormal bulge in the arteries that supply blood to the brain, are prone to rupture and can cause hemorrhagic stroke. Physicians can treat CA by blocking blood flow to the aneurysmal sac via clipping of the aneurysm neck via open procedure, or endovascular occlusion of the aneurysm with embolic materials to promote thrombus formation to prevent further inflow of blood into the aneurysm. Endovascular treatment options for CA still have significant limitations in terms of safety, usability in coagulopathic patients, and risks of device migration. Bioactive embolic therapies, consisting of non-toxic bioresorbable materials that encourage the growth of neointima across the aneurysm neck, are needed to improve the healing of CA. In this work, the bioinspired silk-elastinlike protein-based polymer (SELP 815K), was used to embolize aneurysms in a rabbit elastase model. SELP 815K effectively embolized the model aneurysms in vivo, achieving >90% occlusion, using commercial microcatheters. No device-associated adverse effects were observed in any of the animals, and SELP 815K showed no cytotoxicity. SELP embolization did not show any deleterious effects to local tissues, and features consistent with reendothelialization of the aneurysm neck were noted in histological examination one-month post-embolization. SELP 815K shows promise as an embolic treatment for unruptured CA. STATEMENT OF SIGNIFICANCE: Unruptured cerebral aneurysms are present in approximately 3% of the population, with a fatality rate of up to 65% upon rupture. In this work a silk-elastinlike protein polymer (SELP) is explored as a liquid embolic for occlusion of cerebral aneurysms. This embolic exists as a liquid at room temperature before rapidly forming a gel at physiological temperature. This shape filling property was used to successfully occlude cerebral aneurysms in rabbits, with stable occlusion persisting for over thirty days. SELP occlusions show evidence for reendothelialization of the aneurysm sac and provide an opportunity for delivery of bioactive agents to further improve treatments.
颅内动脉瘤（CA）是供应大脑血液的动脉异常膨出，容易破裂并导致出血性中风。医生可以通过夹闭动脉瘤颈部来治疗 CA，通过开放手术阻断血流进入动脉瘤囊，或通过使用栓塞材料对动脉瘤进行血管内闭塞，以促进血栓形成，防止血液进一步流入动脉瘤。CA 的血管内治疗选择在安全性、在凝血障碍患者中的可用性以及器械迁移风险方面仍然存在显著局限性。需要生物活性栓塞疗法，由无毒的可生物吸收材料组成，这些材料可促进新内膜在动脉瘤颈部生长，以改善 CA 的愈合。在这项工作中，使用仿生丝弹性蛋白样蛋白基聚合物（SELP815K）栓塞兔弹性蛋白酶模型中的动脉瘤。SELP815K 使用商业微导管有效地栓塞了体内模型动脉瘤，实现了 >90%的闭塞。在任何动物中都没有观察到与器械相关的不良反应，并且 SELP815K 没有细胞毒性。SELP 栓塞对局部组织没有任何有害影响，并且在栓塞后一个月的组织学检查中观察到与动脉瘤颈部再内皮化一致的特征。SELP815K 有望成为未破裂 CA 的栓塞治疗方法。 意义声明：未破裂的颅内动脉瘤在人群中约占 3%，破裂后的死亡率高达 65%。在这项工作中，研究了一种丝弹性蛋白样蛋白聚合物（SELP）作为液体栓塞剂来闭塞脑动脉瘤。这种栓塞剂在室温下呈液体状态，在生理温度下迅速形成凝胶。这种形状填充特性被用于成功地闭塞兔脑中的动脉瘤，稳定的闭塞持续超过三十天。SELP 闭塞显示出动脉瘤囊再内皮化的证据，并为进一步改善治疗方法提供了输送生物活性药物的机会。
