Cerebral aneurysms are dilations in intracranial arteries that can rupture, leading to fatal hemorrhagic stroke. Current aneurysm treatments involve the implantation of catheter-based endovascular coils and meshes, but many of them result in unfavorable primary outcomes. This study developed an injectable multi-functional liquid embolic agent (LEA) using F88-dimethacrylated (FDMA) polymer that allows for the body’s natural mechanisms to heal the aneurysm with personalized biodegradation. Upon heating, FDMA micelles group together and entangle, resulting in mechanically strong physical gelation. Chemical crosslinkers ammonium persulfate (APS) and TEMED enhance the long-term stability of the hydrogel, while iohexol acts as a contrast agent.
Aiming at developing a polymer system that is deliverable in vivo, cooled FDMA solution must be injectable through a microcatheter. Gelation must occur at the optimal time and temperature so as not to solidify prematurely or remain liquid within the aneurysm. Various concentrations of FDMA and TEMED were tested in vitro to determine the optimal concentration for injectability. To simulate interventional treatment, the LEA was injected into a brain aneurysm model.
Upon gelation and crosslinking, hydrogels swell in situ, posing a significant risk for compression or rupture. FDMA hydrogel swelling was demonstrated to be dependent on polymer concentration, and the addition of iohexol significantly decreased initial swelling. Furthermore, hydrogels submerged in flowing saline exhibited less swelling than those submerged in static saline due to inter-micellar entanglements.
The embolic agent must also enable vascular remodeling and endothelialization in a controlled manner. Thus, cell adhesion and porosity are vital. Imagery of fibrinogen-soaked gel suggested that natural levels of fibrinogen make the cross-linked FDMA sufficiently cell adhesive . 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.
Future studies will involve studies in rabbit models to determine the efficiency and the rates of endothelization.

Ruth Pereira

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