SBIR-STTR Award

The long-term objective of this research program is to improve the care of patients harboring unruptured as well as ruptured intracranial aneurysms. Unruptured aneurysms are present in approximately 6 to 10 million Americans. An estimated 30,000 of those aneurysms will rupture annually resulting in about 40% fatality. The most modern techniques for aneurysm treatment include minimally invasive, nonsurgical approaches using platinum coils. While these coils decrease the potential negative impact on patients compared to open brain surgery, serious shortcomings remain with this endovascular approach. The most critical of these failures is due to insufficient packing of the aneurysm resulting in “compaction” of the coil mass, in which the aneurysm re- opens over time and requires re-treatment. Another serious drawback of current coils is the inert nature of platinum, which fails to promote tissue growth. This significantly prolongs healing time and increases chances of complications such as inflammation or recurrence by allowing more time for compaction. To address these issues and improve aneurysm healing, we developed a device composed of a highly fibered polymer jacket containing a radiopaque coil. Initial animal trials have shown this device to accelerate healing due to several advantageous features. First of these is implementation of highly thrombogenic fibers to construct the textile outer surface that promotes connective tissue growth both inside the aneurysm and at the neck. Secondly, the soft outer jacket is compressible yet elastic, which allows for a higher packing density to counteract compaction. Thirdly, early animal study results show robust healing with little to no inflammation at one month. The research described in this application will demonstrate safety and efficacy of this new approach to permanently healing intracranial aneurysms. We will apply a well-described rabbit model of aneurysms to show that a highly-fibered device improves tissue growth, without increased risk of stroke, and that the healing within the aneurysms is improved as compared to “gold standard” platinum coils. If successful, this translational research program will directly improve patient outcomes.

Public Health Relevance Statement:
PROJECT NARRATIVE (Relevance) If successful, his research proposal will substantially improve treatment of cerebral aneurysms, as well as other vascular malformations, using a conformable, highly-fibered embolization device which improves healing via minimally invasive techniques.

NIH Spending Category:
Bioengineering; Brain Disorders; Cerebrovascular; Neurosciences; Stroke

Project Terms:
Address; Adverse event; Affinity; American; Aneurysm; Animals; base; Berry Aneurysm; Biological; Blood Vessels; brain surgery; Caliber; Catheters; Cerebral Aneurysm; Characteristics; Chronic; Clinical; Clinical Trials; Collagen; Connective Tissue; dacron; density; Deposition; design; Development; Devices; Elastases; Endothelium; Ensure; experience; experimental study; Extracellular Matrix Proteins; Failure; Feedback; Fiber; Friction; Future; Generations; Goals; Gold; Growth; healing; Hemorrhage; Hemostatic function; Histologic; Histology; Hydrogels; implantation; improved; improved outcome; in vivo; Incidence; Inflammation; Intracranial Aneurysm; Legal patent; malformation; Metals; Methods; minimally invasive; Modeling; Modernization; Modification; Nature; Neck; neurovascular; novel; novel strategies; off-patent; Operative Surgical Procedures; Oryctolagus cuniculus; Outcome; Pathway interactions; Patient Care; Patient-Focused Outcomes; Patients; Performance; Phase; Physical assessment; physical property; Platinum; Polymers; Positioning Attribute; Positron-Emission Tomography; preclinical study; Process; programs; Property; prototype; Recurrence; Research; Research Personnel; Research Proposals; response; Retreatment; Risk; Rupture; Safety; scaffold; standard of care; stroke risk; Surface; Techniques; Textiles; Therapeutic; Therapeutic Embolization; thrombogenesis; Thrombus; Time; Tissues; translational research program; Vascular Graft; Work

Intracranial aneurysms are present in approximately 6-10 million Americans. These aneurysms frequently result in rupture—a devastating outcome which is fatal in roughly 50% of cases. The standard technique for aneurysm treatment involves minimally invasive, endovascular treatment using platinum coils. While endovascular coiling of aneurysms is a proven method that is associated with better outcomes than open brain surgery, serious shortcomings remain. The most critical of these failures is due to insufficient packing of the aneurysm, resulting in “compaction” of the coil mass, a phenomenon which facilitates reopening of the aneurysm over time and necessitates retreatment. Another serious drawback of current coils relates to the inert nature of platinum which fails to promote endothelial growth. This significantly prolongs healing time and increases the likelihood of complications such as inflammation and recurrence. To address these issues and improve aneurysm healing, we have developed a device composed of a highly- fibered polymer jacket containing a radiopaque coil which is designed to provide an optimal platform for endothelialization: the ThromboTube. In our Phase I SBIR proposal, we validated the first generation ThromboTube in a well-established rabbit aneurysm model using Axium MicroFX Nylon fibered coils as the predicate device. The results were promising, demonstrating safety equivalence, higher neck healing score, no sign of compaction, greater endothelialization at the neck/parent vessel interface, and thrombus formation and cell growth over the entirety of the device rather than just at the points of contact with the aneurysm. In light of these promising results, we propose a Phase II SBIR application to expand upon our previous work and achieve commercialization of the ThromboTube. To meet these goals, we will carry out the following objectives: 1) prepare for 510(k) submission of the ThromboTube and begin small-scale manufacturing for a limited product launch; 2) establish a second generation device—the Gen2 ThromboTube—based on physician feedback from our Phase I SBIR; 3) compare the safety and efficacy of the Gen2 ThromboTube to Axium MicroFX fibred coils in an elastase-induced rabbit aneurysm model; and 4) submit a 510(k) application of the Gen2 ThromboTube. Completion of this proposal will result in a portfolio of commercially viable devices capable of accelerating healing and improving outcomes of both unruptured and ruptured intracranial aneurysms.

Public Health Relevance Statement:
PROJECT NARRATIVE Intracranial aneurysms are present in roughly 2% of citizens in the United States and frequently result in rupture—a catastrophic event that has a mortality rate of roughly 50%. Endovascular coiling is the most common method for treating intracranial aneurysms, but current methods promote aneurysm healing very slowly and are associated with alarming rates of recurrence and often require retreatment. To address this gap in clinical care and promote better patient outcomes, Neurogami Medical has designed a novel, highly-fibred coil system that promotes better endothelial coverage and faster aneurysm healing than the leading fibered coil system.

Project Terms:
Address; Adverse event; American; Aneurysm; Animal Model; Arteries; base; Blood; Blood capillaries; brain surgery; Caliber; cell growth; Cerebral Aneurysm; Characteristics; clinical care; Clinical Trials; clinically relevant; Collagen; commercialization; Connective Tissue; dacron; Data; Deposition; design; Development; Devices; Elastases; Electrodes; Endothelium; Engineering; Ensure; Event; Extracellular Matrix Proteins; Failure; Feedback; Fiber; Fibroblasts; Filler; Fright; Generations; Goals; Growth; healing; Hemostatic function; Histologic; Implant; improved; improved outcome; in vivo; Inflammation; Intracranial Aneurysm; Length; Light; Medical; meetings; metallicity; Methods; minimally invasive; Modeling; monocyte; mortality; Nature; Neck; Needles; next generation; novel; Nylons; Oryctolagus cuniculus; Outcome; Parents; Patient Care; Patient-Focused Outcomes; Patients; Performance; Phase; Physicians; Platinum; Polymers; Preparation; Recurrence; Regulatory Pathway; Reporting; Retreatment; Rupture; Safety; Small Business Innovation Research Grant; Structure; Survival Rate; System; Techniques; Technology; Test Result; Testing; Thrombus; Time; Tube; United States; usability; Vision; Voice; Work