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.
