Enhanced endothelialization of nanomatrix coated flow diverter for intracranial aneurysms

Approximately 3% of the population has unruptured cerebral aneurysms, approximately 6 million people in the US. About 30,000 ruptures per year, with devastating consequences. About 40% of patients with ruptured aneurysms die, and 4 of 7 who survive have significant disabilities. To address this issue, several devices have been developed that can be implanted to prevent aneurysm rupture. Flow diverters are one such device that are increasingly being used to cover the neck of the aneurysm providing more durable occlusion. However, until endothelialization and aneurysm occlusion has occurred patients are at increased risk of thromboembolic complications and increased intracranial hemorrhage due to necessary dual antiplatelet therapy. We have developed a BionanomatrixTM coating that mimics the characteristic properties of native endothelium. Thus, we hypothesize that the BionanomatrixTM coating on the flow diverter can enhance endothelial coverage and accelerate aneurysm closure. The coating provides sustained release of nitric oxide (NO), thus recruiting and retaining endothelial cells. It also incorporates an endothelial cell adhesive ligand that promotes endothelial cell retention and migration. The BionanomatrixTM is comprised of a biocompatable peptide-based material and is coated on the flow diverters by simple water evaporation. This coating method minimizes the risk of inflammatory responses. This Phase II SBIR provides several important studies to progress this new coating through the necessary stages to achieve FDA approval. This will include 1) scale up and optimization of the manufacturing process, long term stability of the BionanomatrixTM coating, and packaging validation and 2) assessment of the BionanomatrixTM coating efficacy and safety in a rabbit aneurysm model for 2 and 6 months. In collaboration with Dr. Kadirvel’s group at the Mayo Clinic, in vivo assessment will verify that the BionanomatrixTM coating improves endothelial coverage of flow diverters compared to a standard flow diverter in a rabbit aneurysm model. In collaboration with NAMSA, the stability of the BionanomatrixTM coating and packaging validation will be evaluated following ISO and ASTM guidelines which is critical for FDA application. Development of the BionanomatrixTM coating that enhances occlusion of aneurysms and healing over the flow diverters may have significant impact on the treatment of patients with brain aneurysms. With successful completion of Phase II, we plan to move forward in Phase IIB towards IDE submission.