Control Release and Diffusion-Reaction Kinetics of Genipin-Eluting Fibers Using an in Vitro Aneurysm Flow Model

The minimally invasive treatment of intracranial aneurysms by endovascular coiling is attractive yet faces challenges related to the degradation of fibrin clots in the aneurysm sac over time. Fibrin gels cross-linked with genipin exhibit enhanced mechanical and chemical stability, but there are many unknowns related to best practices for delivery from endovascular devices and subsequent integration of cross-linkers with the nascent clot. Here, we describe the in vitro characterization of genipin-eluting polymer fibers prepared by coextrusion with poly(ethylene-co-vinyl acetate). Genipin incorporation and release from these fibers are characterized by various gravimetric and spectroscopic techniques. Genipin release adheres to Higuchi kinetics with Higuchi constants varying between (2.44 ± 0.83) × 10^-7 and (8.41 ± 0.82) × 10^-7 mol·h^-0.5 depending on genipin loading and vinyl acetate concentration in the polymer matrix. The diffusion-reaction kinetics of genipin released from polymeric fibers within fibrin hydrogels was investigated using an in vitro aneurysm flow model. Spatiotemporal maps of genipin cross-linking density in fibrin gels produced by absorbance measurements suggest that genipin cross-link concentrations up to 9,993.87 ± 909.01 μM can be achieved. This work describes relevant diffusion-reaction parameters of genipin in fibrin gels and establishes the viability of genipin-eluting fibers as a platform for improving endovascular embolization of intracranial aneurysms.