Polysaccharide Hydrogel Fillers for Arteriovenous Malformation

多糖水凝胶填充剂治疗动静脉畸形

• 批准号: 7325832
• 负责人: Weiliam Chen
• 金额: $ 17.83万
• 依托单位: ENDOMEDIX, INC.
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-09-07 至 2009-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7325832
• 关键词: Adhesiveness; Adhesives; Alcohols; Arterial Injury; Arteries; Arteriovenous malformation; Biocompatible; Biological; Blood Vessels; Brain; Carbohydrates; Cardiovascular system; Catheters; Cerebrum; Chitosan; Class; Clinical; Clinical Research; Coagulation Process; Congenital arteriovenous malformation; Contracts; Cyanoacrylates; Cyclic GMP; Defect; Dissection; Ethylene; Ethylenes; Excision; Family suidae; Filler; Future; Goals; Hand; Hyaluronan; Hydrogels; In Situ; In Vitro; Infusion procedures; Ischemic Stroke; Lesion; Liquid substance; Modeling; Modification; Neurologic; Operative Surgical Procedures; Organic solvent product; Outcome; Performance; Phase; Polysaccharides; Precipitation; Preparation; Property; Pulmonary Embolism; Radiosurgery; Recommendation; Risk; Rupture; Side; Small Business Funding Mechanisms; Small Business Innovation Research Grant; Solvents; Spinal Cord; Staging; Symptoms; Therapeutic; Therapeutic Embolization; Time; Tissues; Validation; Veins; Venous; acetylcellulose; aqueous; base; biomaterial compatibility; blood perfusion; cytotoxicity; efficacy evaluation; improved; in vivo; response; vascular bed

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.

描述（由申请方提供）：脑和脊髓动静脉畸形（AVM）是由动脉与静脉的异常和直接连接组成的循环系统缺陷。血管内栓塞，作为治疗AVM的最近出现的一类疗法，通常涉及导管输注和随后将有机溶剂溶解的聚合物材料注射到畸形血管床中导致其闭塞的沉淀，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手术的更好替代方案，但仍存在重大局限性和风险，导致其作为该领域的领导者缺乏普遍接受。栓塞剂在缺乏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性和可生物降解的原位可胶凝碳水化合物水凝胶，不受目前可用液体栓塞剂的限制，用于AVM填充。水凝胶将提供优于传统试剂的性能益处，因为：（i）最短的制备时间，（ii）在脉管系统内快速凝胶化，（iii）对组织的粘附性和内聚性，其允许血管闭塞但使堵塞导管的风险最小化，以及（iv）无细胞毒性。将生产足够的临床级材料用于未来的体内和临床研究。在猪AVM模型中进行体内有效性评价后，将结束该项目。该I期SBIR项目将为开发用于AVM治疗的液体栓塞水凝胶奠定基础。