An In Situ Curing, Shear-Responsive Biomaterial Designed for Durable Embolization of Microvasculature

Abstract

Endovascular embolization is a minimally-invasive technique whereby blood vessels supplying pathological structures are selectively occluded with various embolic agents. In many scenarios, it is desirable for the embolic to distally penetrate to the level of the microvasculature, which maximizes devascularization. Existing agents exhibit inconsistent distal penetration and have other limitations including tendency for proximal reflux, patient pain during infusion, lack of fluoroscopic radiopacity, potential for catheter adhesion, susceptibility to recanalization, and other usability challenges. NeoCast is an in situ curing, solvent-free, non-adhesive biomaterial composed of polydimethylsiloxane, bismuth trioxide, and fumed silica that possesses shear-responsive properties enabling manual injectability through commercially-available microcatheters with large and small diameter lumens. Here, embolization performance with and without flow arrest, in both arterial and venous preclinical anatomies is reported. NeoCast reproducibly achieves a rate of distal penetration with microvascular occlusion that is superior to existing agents, exhibits excellent fluoroscopic visibility, and provides durable occlusion. There is mild inflammation when NeoCast is infused into blood vessels and absence of neurotoxicity when implanted directly into brain tissue. The engineered NeoCast material is poised to become a next-generation, liquid embolic agent for applications in which distal microvascular occlusion is desired.