PI: Christopher J. Bettinger
University: Carnegie Mellon University
This project will optimize manufacturing techniques to create drug-eluting embolization coils, advanced medical devices to treat intracranial aneurysms (ICA).
ICA are saccular defects in the cerebral vasculature that occur in about 5% of all people and are susceptible to rupture, which can be a deadly event. ICA are typically treated by embolization, a minimally invasive procedure in which coiled millimetric platinum (Pt) wires are endovascularly inserted into the aneurysm sac. Thrombogenic Pt coils induce clot formation, sequester the defect, and reduce the risk of hemorrhagic stroke. Although effective in many cases, poor outcomes in embolized ICA are associated with mechanical compaction and enzymatic digestion of the nascent clot. Clot remodeling induces recanalization and recurrence, which occurs in approximately 20-25% of ICA. Previous strategies to improve the performance of embolization coils include novel geometries to increase the volume fraction of Pt coils in the aneurysm, devices to accelerate clotting or coatings to increase packing volume.
The team proposes a technology where Pt coils deliver genipin, a robust natural small molecule protein crosslinker, locally to the aneurysm sac. Local delivery of genipin will covalently crosslink fibrin networks, increase their mechanical strength, reduce their susceptibility to enzymatic digestion, and increase the likelihood of a successful outcome after embolization. However, the ideal drug delivery geometry and approach to manufacturing these devices has not yet been optimized.
This project will use advanced manufacturing techniques to integrate genipin delivery depots with coils and maximize loading of the active compound to the device. Maximizing the amount of genipin delivered to the aneurysms will optimize crosslinking conditions and increase the overall in vivo efficacy of prospective therapies.