Injectable Hydrogel Capable of In Situ Covalent Crosslinking for Permanent Embolization

Abstract

Vascular embolization provides an effective approach for the treatment of hemorrhage, aneurysms, and other vascular abnormalities. However, current embolic materials, such as metallic coils and liquid embolic agents, are limited by their inability to provide safe, consistent, and controlled embolization. Here, we report an injectable hydrogel that can remain at the injection site and subsequently undergo in situ covalent crosslinking, leading to the formation of a dual-crosslinking network (DCN) hydrogel for endovascular embolization. The DCN hydrogel is simple to prepare, easy to deploy via needles and catheters, and mechanically stable at the target injection site, thereby avoiding embolization of nontarget vessels. It possesses efficient hemostatic activity and good biocompatibility. The DCN hydrogel is also clearly visible under X-ray imaging, thereby allowing for targeted embolization. In vivo tests in a rabbit artery model demonstrates that the DCN hydrogel is effective in achieving immediate embolization of the target artery with long-term occlusion by inducing luminal fibrosis. Collectively, the DCN hydrogel provides a viable, biocompatible, and cost-effective alternative to existing embolic materials with clinical translation potential for endovascular embolization.

Recent Progress in Advanced Hydrogel‐Based Embolic Agents: From Rational Design Strategies to Improved Endovascular Embolization

“…The chemical crosslinking results in fast and stable hydrogel formation with a high mechanical strength based on Michael addition reactions, [25,164,165] Schiff base reactions, [166,167] or photocrosslinking. [35,168] The covalent crosslinking between the polymer chains results in the solidification of hydrogels in situ to occlude the blood vessels.…”

“…In vivo embolization on rabbits further demonstrated that the DCN hydrogels could achieve immediate embolization of the femoral artery with long-term occlusion, which could be ascribed to the efficient hemostatic capability, desirable mechanical properties, and stability of the DCN hydrogels. [25] In another study, Lim et al developed a double-crosslinked alginate-based hydrogel (DAT) for treating aneurysms. The photocrosslinkable alginate was mixed with Ta nanopowder and the mixture was continuously spun into hydrogel microfibers via in situ photocrosslinking, followed by ionic crosslinking using Ca 2+ in the blood (Figure 12B).…”

“…In vivo embolization on rabbits further demonstrated that the DCN hydrogels could achieve immediate embolization of the femoral artery with long‐term occlusion, which could be ascribed to the efficient hemostatic capability, desirable mechanical properties, and stability of the DCN hydrogels. [ 25 ] In another study, Lim et al. developed a double‐crosslinked alginate‐based hydrogel (DAT) for treating aneurysms.…”

“…Fortunately, with the development of hydrogel technology and efficient therapeutic systems, various emerging hydrogel embolic systems, such as injectable versatile hydrogels [25][26][27] and stimuli-responsive hydrogel coils, [28,29] have drawn considerable attention in recent years. The hydrogels consist of 3D network structures with favorable properties including prominent swelling ability, permeability, mechanical strength, and biocompatibility.…”

“…[30][31][32] More importantly, the hydrogels can be rationally tailored by altering their physicochemical properties of the structure and introducing functional components into the polymeric matrix, which endow the hydrogels with the ability to respond to various stimuli including temperature, [33] pH, [34] light irradiation, [35] mechanical stress, [36] and magnetic field. [37] Thereby, the in situ forming hydrogels can be delivered in a flowable sol state using any kind of clinically relevant catheter and can be converted into a nonflowable gel state through in situ crosslinking, [25,38] polymerization, [39] and sol-gel transition. [40,41] It is noteworthy that such deformable hydrogels can be delivered distally into vessels to fill the vasculature with various geometries and sizes.…”