PI: Christopher Bettinger, Materials Science and Engineering

Brain aneurysms are a high-­risk condition in which bulging blood vessels in the brain are at risk of rupture. The mortality rate after rupture is 30­60% if no treatment is administered. Current treatment for both ruptured and unruptured aneurysms includes surgical clipping (exovascular therapy) and catheter-­based interventions (endovascular therapy) including endovascular coiling. With respect to the latter, we are currently advancing an innovative coated-­coil technology that can deliver genipin, a small molecular protein crosslinker, within the aneurysm sac. We posit that sustained release of naturally occurring crosslinking agents delivered from coated endovascular coils will increase the mechanical stiffness of the clots and reduce fibrinolysis. Clots stabilized with genipin crosslinks will resist coil compaction and enzymatic degradation thereby increasing the likelihood of successful treatment by via embolization. Preliminary in vitro and in vivo studies suggest that this approach is promising. However, many open questions remain about the fate of genipin delivered in vivo. This project will use 3-D ­printed in vitro model aneurysm to measure fundamentals of genipin reaction kinetics, determine the chemical composition of genipin­-based crosslinks, and model genipin transport. Spatiotemporal distributions of genipin in 3D-­printed synthetic aneurysm sacs will be predicted and compared to experimental results. In addition to understanding fundamentals of genipin reaction kinetics and genipin crosslink composition, these fundamental studies will provide key data that can be used to design the next-­generation of genipin eluting embolization coils for treating intracranial aneurysms and other diseases such as hepatocarcinoma. Furthermore, a deeper understanding of fundamental processes related to genipin reaction-­diffusion may expand the use of this non­toxic naturally occurring small molecule crosslinker for other applications including stabilizing protein-based scaffolds for regenerative medicine or synthetic matrices for use in controlled release technologies.