Cerebral aneurysms are abnormal dilations of intracranial arteries that, if ruptured, can cause life-threatening hemorrhagic strokes. Current treatments typically involve catheter-based endovascular coils and meshes, but many result in suboptimal outcomes. This study developed an injectable multi-functional liquid embolic agent (LEA) using methacrylated Pluronic polymers (FDMA) that facilitates the body's natural mechanisms to heal the aneurysm with fine-tuned biodegradation. Upon heating, FDMA micelles group together and entangle, resulting in mechanically strong physical gelation. Chemical crosslinkers enhance the long-term stability of the hydrogel, where their composition as well as the composition of the FDMA block were fine-tuned to express different capabilities.
Cooled FDMA solution must be injectable through a microcatheter while capable of gelation at ideal time to prevent premature solidification. Different crosslinking pathways were studied and adjusted. Various concentrations of crosslinking systems, consisting of ammonium persulfate (APS) as the initiator and either TEMED or FeCl₂/Ascorbic acid as the radical decomposition catalysts, were tested in vitro to determine the optimal concentration for injectability.
FDMA hydrogel swelling showed it is dependent on polymer concentration, and the addition of iohexol, an agent that rendered the systems X-ray imaging capabilities, significantly decreased initial swelling, which might pose a risk for a rupture. Furthermore, hydrogels submerged in flowing saline demonstrated less swelling than those submerged in static saline due to inter-micellar entanglements.
Fibrinogen-soaked gel suggested that natural levels of fibrinogen make the cross-linked FDMA sufficiently cell adhesive, much needed for vascular remodeling .Sodium phosphate was effectively employed to control pre-determined porosity.
The biodegradability of the LEA is a vital function of the patient-specific wound healing process. For this purpose, enzymatic FDMA degradation was investigated with incorporation of lactides or MMP-sensitive peptides, capable of adjustable degradation through a specific time period.
Studies in rabbit models determined the efficiency and the rates of endothelization.

Shira Fisher

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