Treatment of arterial aneurysms using an injectable biomaterial

摘要 主动脉瘤破裂的病死率很高。它们可以是纺锤形或球状，也可以是 发生在身体的任何地方。囊性动脉瘤(SA)的发病率和死亡率更高，因为 它们更容易破裂。这些动脉瘤可以是特发性的、医源性的、创伤性的或动脉粥样硬化性的。 病因学。无论原因如何，SA都是高致命性的，需要密切的影像监测和治疗 以防止致命的破裂。目前的医疗实践标准主要是治疗SAS的最低限度- 侵入性血管内介入治疗，如弹簧圈栓塞术。尽管线圈有了很大的进步- 栓塞术，目前的治疗仍然存在严重的问题，包括给药困难， 治疗失败的可能性，以及极端的成本。弹簧圈栓塞术需要一套独特的高度... 在亚毫米级的微型导管内将它们导航到遥远的地点的专门技能，需要精确 部署在脆弱的动脉瘤囊内。因此，这类案件非常冗长，并暴露出患者和 医务人员对高辐射剂量的反应。虽然弹簧圈栓塞术的技术成功率在以下情况下可能会很高 由经验丰富的操作员执行，临床成功率仅达80%，失败往往是由 凝血障碍患者的动脉瘤再通和持续的弹簧圈血流。在……里面 事实上，有凝血障碍的患者死亡的可能性要高出10倍，即使是血管内卷曲。 此外，治疗成本过高；线圈的每个成本可达数千美元，一个典型的病例 每个动脉瘤可能需要4-8个弹簧圈，有时甚至需要几十个弹簧圈。我们假设通过使用切割- 边缘组织工程工具，有可能制造出一种通用的、稳定的、 经久耐用、止血、粘合、价格低廉、不依赖凝血获得临床成功，且所需费用较少 栓塞SAS的专门技能。这种创造性的生物工程方法可能会减少手术时间， 减少辐射暴露，并通过消除对昂贵的 使农村和第三世界国家的医院能够获得这种技术的清单。我们的目标是开发一种 开创性剪切稀释法填充动脉瘤囊的微创生物材料平台 基于我们丰富的初步数据的生物材料(STB)。我们将开发用于血管内投放的STB 通过导管(目标1)并改进STB在体外动脉瘤中的生物相容性、粘附性和性能 模型(目标2)。最后，我们将在猪的动脉瘤模型(目标3)中测试工程的STB，模拟 人体动脉瘤的结构。

Abstract Arterial aneurysm rupture has a very high fatality rate. They can be fusiform or saccular in shape and can occur anywhere in the body. Saccular aneurysms (SAs) carry a greater risk of morbidity and mortality because they are more prone to rupture. These aneurysms can be idiopathic, iatrogenic, traumatic, or atherosclerotic in etiology. Regardless of the cause, SAs are highly-lethal and warrant close imaging surveillance and treatment to prevent a fatal rupture. The current standard of medical practice is primarily to treat SAs with minimally- invasive endovascular interventions such as coil embolization. Despite substantial advancements in coil- embolization technology, serious issues remain with current treatments, including difficulty in administration, the possibility of treatment failure, and extreme cost. Coil embolization requires a unique set of highly- specialized skills to navigate them within sub-millimeter micro-catheters to distant sites and require precise deployment within fragile aneurysm sacs. As a result, such cases are very lengthy and expose patients and medical staff to high radiation doses. While technical success of coil embolization may be high when performed by experienced operators, clinical success reaches only 80%, with failures often resulting from recanalization of the aneurysm and persistent flow through the coils in patients with coagulation disorders. In fact, death is 10 times more likely to occur in patients with coagulopathy, even with endovascular coiling. Furthermore, cost of treatment is excessive; coils can cost many thousands of dollars each and a typical case may require 4-8 coils per aneurysm and in some cases many dozens. We hypothesize that by using cutting- edge tissue engineering tools, it may be possible to produce a universal embolization biomaterial that is stable, durable, hemostatic, adhesive, inexpensive, does not rely on coagulation for clinical success, and requires less specialized skills to embolize SAs. This creative, bioengineering approach may reduce procedure time, decrease radiation exposure, and reduce world-wide morbidity and mortality by removing the need for a costly inventory enabling rural and 3rd world country hospitals to access such technology. We aim to develop a minimally invasive biomaterial-based platform to fill aneurysm sacs using groundbreaking shear-thinning biomaterials (STBs) based on our rich preliminary data. We will develop STBs for endovascular delivery through catheters (Aim 1) and refine STB biocompatibility, adhesiveness, and performance in in vitro aneurysm models (Aim 2). Finally, we will test the engineered STBs in porcine aneurysm models (Aim 3) that mimic the structure of aneurysms in humans.