In vitro Implementation of Photopolymerizable Hydrogels as a Potential Treatment of Intracranial Aneurysms.

Oriane Poupart,Riccardo Conti,Christophe Moser,Katja M Nuss,Pascal J Mosimann,Dominique P Pioletti,Hansjörg Grützmacher,Andreas Schmocker

doi:10.3389/fbioe.2020.00261

Abstract

Intracranial aneurysms are increasingly being treated with endovascular therapy, namely coil embolization. Despite being minimally invasive, partial occlusion and recurrence are more frequent compared to open surgical clipping. Therefore, an alternative treatment is needed, ideally combining minimal invasiveness and long-term efficiency. Herein, we propose such an alternative treatment based on an injectable, radiopaque and photopolymerizable polyethylene glycol dimethacrylate hydrogel. The rheological measurements demonstrated a viscosity of 4.86 ± 1.70 mPa.s, which was significantly lower than contrast agent currently used in endovascular treatment (p = 0.42), allowing the hydrogel to be injected through 430 μm inner diameter microcatheters. Photorheology revealed fast hydrogel solidification in 8 min due to the use of a new visible photoinitiator. The addition of an iodinated contrast agent in the precursor contributed to the visibility of the precursor injection under fluoroscopy. Using a customized light-conducting microcatheter and illumination module, the hydrogel was implanted in an in vitro silicone aneurysm model. Specifically, in situ fast and controllable injection and photopolymerization of the developed hydrogel is shown to be feasible in this work. Finally, the precursor and the polymerized hydrogel exhibit no toxicity for the endothelial cells. Photopolymerizable hydrogels are expected to be promising candidates for future intracranial aneurysm treatments.

Highlights

Intracranial aneurysms (IAs) are saccular dilatations or outpouchings of brain arteries that are prone to rupture, causing death or severe morbidity in over half of the patients (Medical Advisory Secretariat, 2006)
While non-adhesive ethylvinyl-alcohol (EVOH) copolymer agents precipitate over several minutes (Kilani et al, 2015), the dimethyl sulfoxide (DMSO) solvent they contain can induce vasospasm and angionecrosis depending on the concentration and volume injected (Takeda et al, 2015; Onyx R Liquid Embolic System) which is especially harmful if left to stagnate in such a restricted space as an aneurysm
To address the challenge of inserting a photoactivable hydrogel into an IA, we present the development of a light-conducting microcatheter combined with an illumination module to guide visible light to the aneurysm

Summary

Introduction

Intracranial aneurysms (IAs) are saccular dilatations or outpouchings of brain arteries that are prone to rupture, causing death or severe morbidity in over half of the patients (Medical Advisory Secretariat, 2006). Photopolymerizable Hydrogels for Intracranial Aneurysms clipping (Molyneux et al, 2015; Smith et al, 2015; Hulsbergen et al, 2019) Adjunctive devices such as flow diverting stents may decrease this risk by promoting endothelial growth at the neck of the IA (Ravindran et al, 2019) but currently require dual antiplatelet medication to avoid parent artery thrombosis, thereby increasing the risk of bleeding. Using liquid embolic agents to treat aneurysms is not a new concept (Brassel and Meila, 2015). They allow the whole volume of aneurysms of any shape or size to be filled. Leakage and solidification in the parent artery remains a serious potential complication, even with balloon assistance

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