Hydration-Driven Self-Gelling Particulate Embolic Agent for Precise and Stable Occlusion of Hemorrhagic Vessels with Collateral Circulation.

Abstract

Embolization of hemorrhagic small vessels with collateral circulation remains challenges, as conventional liquid agents often cause nontarget embolization and particulate agents are prone to recanalization. Herein, we develop an injectable embolic system (PP/DMSO/I) based on hydration-driven self-gelling polyethylenimine/poly(acrylic acid) (PP) particles that seamlessly combines the controllable embolic size of particulate agents with the stable occlusion of liquid agents. Upon intravascular delivery, DMSO transports size-sieved PP particles to the target blood vessel, where they aggregate due to size-restricted trapping, achieving precise embolization without distal migration. Subsequent solvent exchange with blood triggers rapid hydration and fusion of PP particles into a continuous and adaptive hydrogel in situ that definitively occludes the lumen. In a typical hemorrhagic collateral circulation model (hemorrhagic point in anastomotic arcade between mesenteric artery of the rabbit), PP/DMSO/I achieves superior hemostasis (blood loss: 2.1 ± 0.3 g), significantly outperforming commercial particulate embolic agent (3.7 ± 0.4 g) and matching the efficacy of commercial liquid embolic agents (2.3 ± 0.4 g and 2.1 ± 0.6 g). Crucially, unlike commercial liquid embolic agent, it eliminated the risk of nontarget embolization and distal infarction. This hydration-driven self-gelling particulate embolic system represents a paradigm shift in embolization therapy, offering a precise, durable, and safe solution for managing hemorrhage in complex vascular networks.