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.
Public Health Relevance Statement: Brain aneurysms carry the devastating risk of rupture, leading to death or permanent disability. Currently available flow diverters used to treat aneurysms are limited by a significant risk of thromboembolic complications until endothelialization and aneurysm closure has occurred. Medications to prevent clotting place patients at increased risk of bleeding during these several months awaiting endothelial coverage. Endomimetics, LLC has developed a novel nanomatrix, which, when coated onto coils, could enhance endothelialization and reduce the risk of embolic stroke or brain hemmorhage.
NIH Spending Category: Brain Disorders; Cerebrovascular; Neurosciences; Stroke
Project Terms: Adhesions; Adhesives; Agreement; Aneurysm; Animals; Arteries; base; biomaterial compatibility; Blood Platelets; Brain; Brain Aneurysms; Case Series; Cell-Matrix Junction; Cells; Cerebral Aneurysm; Cessation of life; Characteristics; Chronic; Clinic; Clinical; clinical care; Coagulation Process; Collaborations; Data; Development; Devices; disability; Elastases; Elements; embolic stroke; Endothelial Cells; Endothelium; Environment; Evaluation; evaporation; Fright; General Population; Genes; Growth; healing; Hemorrhage; Histologic; improved; In Vitro; in vivo; industry partner; Inflammatory; Inflammatory Response; Infrastructure; innovation; Intracranial Aneurysm; Intracranial Hemorrhages; Investigation; Legal patent; Letters; Ligands; Mediating; metallicity; Methodology; Methods; migration; minimally invasive; Modeling; monocyte; Morbidity - disease rate; Neck; Nitric Oxide; novel; off-patent; Oryctolagus cuniculus; Outcome; Parents; Patients; Peptides; Pharmaceutical Preparations; Phase; phase 1 study; Population; Positioning Attribute; pre-clinical; prevent; Process; Production; Property; quality assurance; recruit; Recurrence; Research; Resources; Retreatment; Risk; risk minimization; Rupture; Ruptured Aneurysm; scale up; Site; Small Business Innovation Research Grant; Structure; Therapeutic Embolization; Thromboembolism; thrombogenesis; Thrombus; Tissues; Water; Work
