Polysaccharide Hydrogel Fillers for Arteriovenous Malformation

描述（由申请人提供）：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直接连接组成。血管内栓塞作为最近出现的一类治疗avm的治疗方法，通常涉及导管输注，随后将溶解聚合物材料的有机溶剂沉淀注入畸形血管床，导致其闭塞，从而解决神经系统相关症状。尽管这种治疗方式通常被认为是外科切除和放射手术的更好选择，但其主要局限性和风险导致其在该领域缺乏普遍认可。栓塞剂在没有经验的人手中使用是困难和危险的，这导致了对这些药物的普遍怀疑。一种易于使用、更安全、更有效的药物将增加使用并拓宽应用范围。该项目的目标是开发一种生物相容性和可生物降解的原位可凝胶性碳水化合物水凝胶，没有目前可用的液体栓塞剂的限制，用于AVM填充。水凝胶将提供优于传统药物的性能优势，因为：(i)制备时间最短，（ii）血管内快速凝胶化，（iii）对组织的粘附性和内聚性，允许血管闭塞，但将堵塞导管的风险降至最低，以及（iv）无细胞毒性。将为未来的体内和临床研究生产足够的临床级材料。本项目将在猪AVM模型的体内疗效评估后结束。第一阶段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.