A new radiopaque embolizing agent for the treatment of endoleaks after endovascular repair: Influence of contrast agent on chitosan thermogel properties

摘要

A new injectable radiopaque embolizing agent has been developed, based on chitosan thermogelling properties. Different commercial contrast agents (Isovue?, Visipaque?, and Conray?) were associated with chitosan-β-glycerophosphate. Their impact on gelation kinetic, mechanical properties, radiopacity, and cytotoxicity was tested to evaluate the best candidate and its feasibility for the treatment of endoleaks after endovascular aneurysm repair (EVAR). Addition of contrast agents did not prevent gelation at body temperature, but it significantly increased the viscosity of the solution before gelation, delayed gelation, and reduced the gelation rate. However, using chitosan with a high degree of deacetylation and 20 vol % contrast agent made it possible to obtain a gel with rapid gelation that was visible during X-ray based guided intervention. Hydrogels exhibit relatively low mechanical properties, which are only slightly modified by the addition of contrast agents. In vitro studies have demonstrated rapid release of contrast agents from hydrogels when immersed in a saline solution (>50% within 4 h). This is suitable for embolization, as radiopacity is required only to follow the embolization procedure, while long-term radiopacity would hamper further imaging and endoleak detection. Cytotoxicity and osmolality testing of extracts demonstrated some toxicity of products released by the gel during the first few hours, which is mainly related to their hypertonicity. After the first 24 h incubation, hydrogels released no more cytotoxic compounds, suggesting that the hydrogel rapidly becomes biocompatible. Altogether, this study suggests that the new radiopaque thermogels present interesting characteristics as embolizing agents for EVAR, although their mechanical properties require improvement.