(83d) A Novel Bioactive Hydrogel for Aneurysm Occlusion

Approximately 400 million people harbor unruptured saccular aneurysms. In the US, 30,000 aneurysms rupture each year, causing stroke, permanent nerve damage, or subarachnoid hemorrhage. The current endovascular embolization method using platinum coils cannot treat wide-necked, large, or giant aneurysms. Other limitations of platinum coils include the inability to fill the aneurysm completely, coil herniation into the parent vessel, and delayed thrombus and organized tissue formation, which leave the area susceptible to recanalization and rupture. To address these disadvantages, we have developed a bioactive gel that forms in situ to conform and adhere to any aneurysm geometry, provide adequate mechanical support, and divert blood flow to heal the area with controlled cell adhesion and migration. We have synthesized a biocompatible, non-degradable, radiopaque, photopolymerizable polyvinyl alcohol (PVA) embolic material for in situ gelation. Evaluation of the material properties, including elasticity and polymerization time, was performed to determine the feasibility of using PVA for aneurysm treatment. We have created an in vitro aneurysm model with a poly(dimethylsiloxane) (PDMS) mold attached to glass to analyze in situ polymerization of the material as well as the ability of the gel to withstand hemodynamic forces. We have also conjugated bioactive and adhesive molecules, such as monoclonal mouse anti-human vascular cell adhesion molecule-1 (aVCAM-1) and arginine-glycine-aspartate-serine (RGDS) peptides, to promote cell adhesion, migration, and recruitment to facilitate aneurysm healing. This new bioactive strategy for aneurysm treatment addresses both mechanical and biological factors that may reduce the incidence of rupture.