Enhanced endothelialization of nanomatrix coated flow diverter for intracranial aneurysms

Project: Research project

Project Details

Description

Approximately 3% of the population has unruptured cerebral aneurysms, approximately 6 million people in the US. About 30,000 rupture per year, with devastating consequences. About 40% of patients with ruptured aneurysms die, and 4 of 7 who survive have significant disabilities. Coil embolization therapy is associated with a high rate of recurrence. Flow diverters 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 nanomatrix coating that mimics the characteristic properties of native endothelium. Thus, we hypothesize that the nanomatrix coating on the flow diverter can enhance endothelial coverage and accelerate aneurysm closure. The coating provides sustained release of nitric oxide (NO) over 2 months, thus recruiting and retaining endothelial cells. It also incorporates an endothelial cell adhesive ligand that promotes endothelial cell retention and migration. The bionanomatrix is a biocompatable peptide based material and is coated on the coils by simple water evaporation. This coating method minimizes the risk of inflammatory responses. In this Phase I SBIR, we propose to evaluate the coating for flow diverters for treatment of brain aneurysms. This will include 1) characterization of nanomatrix coating; 2) assessment of coating structural integrity; 3) evaluation of endothelial cell attachment, growth and migration; 4) evaluation of platelet adhesion; and 5) evaluation of monocyte adhesion to endothelial cells and expression of monocyte inflammatory genes. In collaboration with Dr. Kadirvel's group at the Mayo Clinic, in vivo assessment will verify that the nanomatrix coating improves endothelial coverage of flow diverters compared to a standard flow diverter in a rabbit aneurysm model. Development of the nanomatrix coating that enhances occlusion of aneurysms and healing over the flow diverters may have significant impact in the treatment of patients with brain aneurysms. With successful completion of Phase I, we plan to move forward in Phase II towards IDE submission.
StatusNot started