SBIR Phase I: Development of an Injectable Shear Thinning Biomaterial for the Treatment of Aneurysms

这个小企业创新研究(SBIR)第一阶段项目的更广泛影响在于开发了一种用于治疗动脉瘤的创新型通用栓塞生物材料，目的是阻止不需要的血液通过身体任何地方的血管流动。最近的报告估计，仅在美国，动脉瘤的发病率就高达600万。仅动脉瘤破裂的死亡率就超过50%；在破裂中幸存下来的人中有66%患有严重残疾。目前对动脉瘤的基准治疗包括弹簧圈栓塞术，即受过培训的放射科医生将卷曲形状的长金属丝推入血管，直到它们被密集填充，以减缓和凝结血液流动。虽然存在治疗选择，但大多数都存在管理困难、治疗失败率高和成本高的问题。拟议的新型剪切变薄生物材料(STB)技术为治疗动脉瘤提供了一种易于使用、成本更低、更安全的替代方案。这种方法有可能减少手术时间，减少辐射暴露，降低世界范围内的发病率和死亡率，并提供进入广泛医院的机会。拟议的项目将产生所需的数据，用于开发一种用于治疗动脉瘤的强大、微创和生物兼容的STB产品。在目标1中，我们将展示STB现成的准备情况，包括在预混合、即用配方中的足够保质期内的稳定性，以及通过ISO-10993框架实现的生物兼容性。这些研究将证明STB的安全性。在目标2中，我们将进行临床前毒理学和性能测试，以证明STB栓塞剂的持久性、安全性和有效性，并使用犬囊性动脉瘤(SA)动物模型来证明优化的STB的生物相容性和成功投放。指标包括在60天的随访期内动脉瘤囊内血流停止和无再通现象。其他待研究的参数包括炎症率、适当的粘连和材料暴露在血流中时的不移动性，目标是成功地(95%)在栓塞术后60天内排除循环，并沿着管腔界面上皮化。这一奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

The broader impact of this Small Business Innovation Research (SBIR) Phase I project lies in the development of an innovative universal embolization biomaterial for the treatment of aneurysms with the goal of stopping undesired blood flow through vessels anywhere in the body. Recent reports estimate aneurysm incidence of 6 million in the US alone. The mortality rate for aneurysm rupture alone are over 50%; 66% of those who survive a rupture suffer from major disabilities. Current benchmark treatments for aneurysms include coil embolization, in which trained radiologists push long metal wires with a coiled shape into the vessel until they are packed densely to slow and clot blood flow. While treatment options exist, most suffer from difficulty in administration, high treatment failure rate, and high cost. The proposed novel shear-thinning biomaterial (STB) technology offers an easy-to-use, cheaper and safer alternative to treat aneurysms. This approach has the potential to reduce procedure time, decrease radiation exposure, reduce world-wide morbidity and mortality, and provide access to a broad range of hospitals. The proposed project will generate the required data for a development of a robust, minimally invasive, and biocompatible STB product for treatment of aneurysms. In Objective 1, we will demonstrate STB off-the-shelf readiness, including stability over an adequate shelf life in a premixed, ready-to-use formulation, and biocompatibility through the ISO-10993 framework. These studies will demonstrate STB safety. In Objective 2, we will conduct preclinical toxicological and performance testing to demonstrate the durability, safety and efficacy of the STB embolic agent using a canine saccular aneurysm (SA) animal model to demonstrate biocompatibility of optimized STBs and successful delivery. Benchmarks include stoppage of blood flow and absence of recanalization within the aneurysm sac in a 60-day follow up time period. Other parameters to be studied include inflammation rates, proper adhesion, and immobility of the material upon exposure to the blood stream, with the goal of successful (95%) exclusion from the circulation up to 60-day post embolization with epithelization along the lumen interface.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.