Polysaccharide Hydrogel Fillers for Arteriovenous Malformation

描述(申请人提供)：脑和脊髓动静脉畸形(AVM)是循环系统的缺陷，由动脉与静脉的异常和直接连接组成。血管内栓塞术是近年来出现的一种治疗脑动静脉畸形的方法，它通常是通过导管输注，然后将溶解了有机溶剂的聚合物注入畸形的血管床内，导致血管床闭塞，从而解决相关的神经症状。尽管这种治疗模式通常被认为是手术切除和放射外科的更好选择，但仍存在重大限制和风险，导致它们作为该领域的领先者缺乏普遍接受。栓塞剂在没有经验的人手中使用是困难和危险的，这导致了人们对这些试剂的普遍怀疑。一种易于使用、更安全、更有效的试剂将增加使用并扩大应用范围。本项目的目标是开发一种生物相容和可生物降解的原位可凝胶碳水化合物水凝胶，而不受现有液体栓塞剂的限制，用于AVM的充填。这种水凝胶将提供比传统试剂更好的性能，因为：(I)最短的准备时间，(Ii)在血管系统内快速凝胶化，(Iii)对组织的粘附性和凝聚力，允许血管闭塞，但将导管堵塞的风险降至最低，以及(Iv)无细胞毒性。将为未来的体内和临床研究提供足够的临床级材料。该项目将在猪AVM模型上进行体内疗效评估后结束。这个第一阶段的SBIR项目将为开发用于AVM治疗的液体栓塞水凝胶奠定基础。

DESCRIPTION (provided by applicant): Brain and spinal cord arteriovenous malformations (AVM) are defects of the circulatory system consisting of abnormal and direct connections of arteries to veins. Endovascular embolization, as a recently emerged class of therapy for treating AVMs, generally involves catheter infusion and subsequent precipitation of an organic solvent dissolved polymeric materials injected into a malformed vascular bed leading to its obliteration, thereby resolving the neurological symptoms associated. Even though this mode of treatment is generally regarded as a better alternative to surgical resection and radiosurgery, there are major limitations and risks leading to their lack of universal acceptance as leader in the field. Embolic agents are difficult and dangerous to use in inexperienced hands contributing to general skepticism of these agents. An easy-to-apply, safer, and more effective agent would increase use and broaden applications. The goal of this project is to develop a biocompatible and biodegradable in situ gelable carbohydrate hydrogel, without the limitations of the liquid embolic agents currently available, for AVM filling. The hydrogel will provide performance benefits over traditional agents because of: (i) minimal preparation time, (ii) rapid gelation within the vasculature, (iii) adhesiveness and cohesiveness to tissues that allow for vascular occlusion but minimize the risk for clogging catheters, and (iv) no cytotoxicity. Sufficient clinical grade materials will be produced for future in vivo and clinical studies. The project will be concluded after performing in vivo efficacy evaluations in swine AVM models. This Phase I SBIR project will set the stage for developing a liquid embolic hydrogel for AVM treatment.