Cerebral aneurysms are arterial dilations that, if ruptured, cause life-threatening hemorrhagic strokes. Current catheter-based treatments often result in suboptimal outcomes and ~ 20% recurrence rate. This study develops an injectable multi-functional liquid embolic agent (LEA) using di-methacrylated Pluronic polymers (FDMA) to facilitate natural aneurysm healing with fine-tuned biodegradation. The LEA is reverse thermo-responsive, transitioning upon heating to form robust gels. Chemical crosslinkers enhance long-term stability, with composition and FDMA block fine-tuned for diverse capabilities. FDMA were crosslinked with ammonium persulfate (APS) as initiator and either Iron Chloride (FeCl2)/Ascorbic acid (AA) or tetramethylethyldiamine (TEMED) as catalyst.

For in vivo delivery, cooled FDMA must be injectable through a microcatheter and gel at an ideal time to prevent premature solidification. This project optimized an injection procedure and identified the ideal gel composition. This procedure involves the liquid agent crosslinking in situ inside a catheter, forming hydrogel coils to fill diverse aneurysm morphologies. Two distinct injection phases are separated by a precise crosslinking wait time. Testing FDMA88 and F88 blends in a silicone aneurysm model assessed injectability. Consistent procedure was paramount for correct crosslinking timing. Gels remained stable in situ within the aneurysm model overnight under flow.

Beyond injection, the LEA integrates other vital functionalities. Hydrogel swelling depended on polymer concentration and other environmental factors. The LEA also promotes controlled endothelialization and vascular remodeling, with fibrinogen-soaked gel suggesting cell adhesion. For tunable wound healing, LEA biodegradability was investigated via insertion of lactides or MMP-sensitive peptides, allowing adjustable degradation.

Injections were conducted in 3D-printed silicone practice vessels with acrylamide coating mimicking blood vessels for verified catheter injection. Studies in rabbit models determined the efficiency and rates of endothelization. The optimal gel demonstrated in vitro stability, enabling successful injections without premature crosslinking.

Ongoing experiments explore injection pressure, with future steps including improving vessel stability and in vivo testing under surgical conditions. Ultimately, this work aims to establish successful aneurysm treatment to improve patient outcomes.

Wenxin Yu

University of Southern California

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