Polysaccharide Hydrogel Fillers for Arteriovenous Malformation

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.