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

该小型企业创新研究（SBIR）第一阶段项目的更广泛影响在于开发一种用于治疗动脉瘤的创新通用栓塞生物材料，其目标是阻止体内任何地方的血管中的不良血流。最近的报告估计仅在美国就有600万例动脉瘤发病率。仅动脉瘤破裂的死亡率就超过50%; 66%的破裂幸存者患有严重残疾。目前动脉瘤的基准治疗包括弹簧圈栓塞，其中受过训练的放射科医生将具有螺旋形状的长金属丝推入血管，直到它们被密集地包裹以减缓和凝结血流。虽然存在治疗选择，但大多数都存在给药困难、治疗失败率高和费用高的问题。提出的新型剪切致稀生物材料（STB）技术提供了一种易于使用、更便宜、更安全的动脉瘤治疗替代方案。这种方法有可能缩短手术时间，减少辐射暴露，降低全球发病率和死亡率，并提供广泛的医院。拟议项目将生成用于治疗动脉瘤的稳健、微创和生物相容性STB产品开发所需的数据。在目标1中，我们将通过ISO-10993框架证明STB的现成可用性，包括预混、即用型制剂在适当有效期内的稳定性和生物相容性。这些研究将证明STB的安全性。在目标2中，我们将使用犬囊状动脉瘤（SA）动物模型进行临床前毒理学和性能试验，以证明STB栓塞剂的耐久性、安全性和有效性，从而证明优化STB的生物相容性和成功输送。基准包括在60天随访时间内动脉瘤囊内血流停止和无再通。其他待研究的参数包括炎症率、适当的粘附性和材料在暴露于血流时的固定性，目标是成功（95%）排除60-该奖项反映了NSF的法定使命，并通过使用基金会的智力价值和更广泛的评估被认为值得支持。影响审查标准。

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.