More than 3% of the population has unruptured cerebral aneurysms, approximately 10 million people in the US. About 30,000 rupture per year, with devastating consequences. More than 30% of patients with ruptured aneurysms die, and 4 of 7 who survive have significant disabilities. Detachable microcoils are now used in more than 70% of treated aneurysms. The risk of recurrence, or recanalization, remains surprisingly high at approximately 20-30%. Various modifications are used clinically with limited evidence that they provide improvement over bare coils. An important factor to improve clinical efficacy of the coils is to enhance endothelization, leading to durable occlusion. We have developed a nanomatrix coating that mimics the characteristic properties of native endothelium. Thus, we hypothesize that the nanomatrix coating on the coil can enhance healing, thereby promoting durable closure of aneurysms. The coating provides sustained release of nitric oxide (NO) over 2 months, thus recruiting and retaining endothelial cells and endothelial progenitor 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 and optimize the coating for platinum coils for treatment of brain aneurysms. This will include optimizing the coating method for this specific device, evaluating physical characteristics of the coating, and assessing effects on endothelial and smooth muscle cell growth. In collaboration with Dr. Kadirvel's group at the Mayo Clinic, the efficacy of this coating will be evaluated in an established rabbit model of aneurysms, compared with bare platinum coils. Development of the nanomatrix coating that enhances occlusion of aneurysms and healing over the microcoils 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: Public Health Relevance: Brain aneurysms carry the devastating risk of rupture, leading to death or permanent disability. Currently available platinum coils used to treat aneurysms are limited by a high rate of recurrence. Endomimetics, LLC has developed a novel nanomatrix, which, when coated onto coils, could enhance endothelialization and reduce the risk of brain aneurysm recurrence.
NIH Spending Category: Brain Disorders; Neurosciences; Stem Cell Research; Stem Cell Research - Nonembryonic - Non-Human
Project Terms: Adhesives; Agreement; Aneurysm; Animals; base; Binding Sites; Biocompatible; Blood; Brain Aneurysms; Cell Differentiation process; cell growth; Cell-Matrix Junction; Cells; Cerebral Aneurysm; Cessation of life; Characteristics; Clinic; Clinical; clinical care; Clinical Data; clinical efficacy; Collaborations; Data; Development; Devices; disability; Elastases; Elements; Endothelial Cells; Endothelium; Environment; Evaluation; evaporation; Fright; good laboratory practice; Growth; Healed; healing; Human; improved; In Vitro; in vivo; industry partner; Inflammation; Inflammatory Response; Intracranial Aneurysm; Legal patent; Letters; Ligands; Mediating; Methodology; Methods; migration; Modeling; Modification; Mortality Vital Statistics; Nitric Oxide; novel; Organic solvent product; Oryctolagus cuniculus; Outcome; Patients; Peptides; Phase; phase 1 study; physical property; Platinum; Population; Positioning Attribute; pre-clinical; Production; Property; public health relevance; quality assurance; Recruitment Activity; Recurrence; Research; Research Infrastructure; Resources; Risk; Rupture; Ruptured Aneurysm; scale up; Site; Small Business Innovation Research Grant; Smooth Muscle Myocytes; spelling; Stem cells; success; surface coating; Technology; Therapeutic Embolization; Tissues; tyrosyl-isoleucyl-glycyl-seryl-arginine; Umbilical vein; United States Food and Drug Administration; Water; Work
