Treatment of arterial aneurysms using an injectable biomaterial

摘要 动脉瘤破裂有很高的致死率。它们可以是梭形或囊状， 发生在身体的任何地方。囊状动脉瘤（SA）具有更高的发病率和死亡率风险，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， 病因学不管是什么原因，SA都是高致命性的，需要密切的成像监测和治疗 以防止致命的破裂目前的医疗实践标准主要是治疗SA， 侵入性血管内介入，如弹簧圈栓塞。尽管在线圈方面取得了重大进展- 栓塞技术，严重的问题仍然与目前的治疗，包括管理困难， 治疗失败的可能性和高昂的费用。弹簧圈栓塞需要一套独特的高度- 专门的技能，将它们在亚毫米微导管内导航到遥远的部位， 在脆弱的动脉瘤囊内展开。因此，这种情况非常漫长，使病人和 医务人员受到高剂量辐射。虽然弹簧圈栓塞的技术成功率可能很高， 由经验丰富的操作者进行，临床成功率仅达到80%，失败往往是由于 凝血障碍患者动脉瘤再通和通过弹簧圈的持续血流。在 事实上，凝血功能障碍患者的死亡率是其他患者的10倍，即使采用血管内弹簧圈栓塞术也是如此。 此外，治疗成本过高;线圈每个可能花费数千美元，并且典型情况下， 每个动脉瘤可能需要4-8个线圈，在某些情况下需要几十个线圈。我们假设通过切割- 边缘组织工程工具，可以生产稳定的通用栓塞生物材料， 耐用、止血、粘合、廉价，不依赖于凝血获得临床成功， 栓塞SA的专业技能。这种创造性的生物工程方法可以减少手术时间， 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。我们的目标是发展一个 基于微创生物材料的平台，使用突破性的剪切稀化填充动脉瘤囊 生物材料（STBs）基于我们丰富的初步数据。我们将开发用于血管内输送的STB 通过导管（目标1），并完善STB的生物相容性、可植入性和体外动脉瘤中的性能 模型（目标2）。最后，我们将在猪动脉瘤模型（目标3）中测试工程STB， 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.