Photomodulated Extrusion as a Localized Endovascular Hydrogel Deposition Method.

ABSTRACT

Minimally invasive endovascular embolization is used to treat a wide range of diseases in neurology, oncology, and trauma where the vascular morphologies and corresponding hemodynamics vary greatly. Current techniques based on metallic coils, flow diverters, liquid embolics, and suspended microspheres are limited in their ability to address a wide variety of vasculature and can be plagued by complications including distal migration, compaction, and inappropriate vascular remodeling. Further, these endovascular devices currently offer limited therapeutic functions beyond flow control such as drug delivery. Herein, a novel in situ microcatheter-based photomodulated extrusion approach capable of dynamically tuning the physical and morphological properties of injectable hydrogels, optimizing for local hemodynamic environment and vascular morphology, is proposed and demonstrated. A shear thinning and photoactivated poly(ethylene glycol diacrylate)-nanosilicate (PEGDA-nSi) hydrogel is used to demonstrate multiple extrusion modes which are controlled by photokinetics and device configurations. Real-time photomodulation of injected hydrogel viscosity and modulus is successfully used for embolization in various vasculatures, including high-flow large vessels and arterial-to-arterial capillary shunts. Furthermore, a generalizable therapeutic delivery platform is proposed by demonstrating a core-shell structured extrusion encapsulating doxorubicin to achieve a more sustained release compared to unencapsulated payload.