Development of Dual-Crosslinking N-Isopropylacrylamide-Based Injectable Hydrogel for Transcatheter Embolization in Swine Model

For decades, endovascular embolization (EE) has been a common technique for the treatment of several vascular abnormalities where the affected vessel is occluded using biocompatible embolic agents. In this work, we developed a NIPAAm-based temperature responsive, dual-crosslinking biocompatible and non-toxic injectable hydrogel system as a liquid embolic agent for EE. The swelling and mechanical properties of the hydrogel were tuned and optimized for its in vivo application. The in vivo study was carried out with nine swine models, including three animals for exploratory study and six animals for acute confirmatory study for the occlusion of surgically created aneurysm and rete mirabile. The polymer hydrogel was delivered into the vascular malformation sites using a catheter guided by angiography. After the injection, the liquid embolic agent was transformed into a solid implant in situ via cross-linking through chemical and thermal processes. During the exploratory study, it was observed that one of the three aneurysms and all the RMs were occluded. During the acute confirmatory study, all the aneurysms and the RMs of six animals were successfully occluded. Overall, our study presents the construction and characterization of a novel injectable hydrogel system capable of successfully occluding vascular malformation in large animals. In the future, after further modification and validation, this material may be used as a liquid embolic agent in clinical studies.