Image-guided thermal ablation (TA), which is less invasive, has been widely applied for treating various kinds of tumors. However, TA still poses the potential risk of thermal damage to sensitive tissue nearby. Therefore, an adjunctive thermoprotective hydrodissection technique with constant injection of 5% glucose (5% Glu) has currently been adopted for clinical application, but this may be hazardous to humans. In this study, a multifunctional hyaluronic acid-based hydrogel (HA-Dc) was developed for hydrodissection. Compared with 5% Glu (the most clinically used solution) and the previously reported F127 hydrogel, the HA-Dc hydrogel was studied in vitro in a porcine liver model and in vivo in a rabbit model and showed good injectability and better tissue retention, stability, and thermoprotective properties throughout the TA procedure. Furthermore, in the preclinical evaluation in a Macaca fascicularis (M. fascicularis) model, HA-Dc showed excellent performance in terms of stricter neuroprotection compared with 5% Glu. In addition, the HA-Dc hydrogel with good biocompatibility and controllable degradation behavior in vivo could be a promising platform for thermal protection during clinical TA procedures.
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