Solvent Exchange Induced In Situ Formed Hydrogel as Liquid Embolic Agents

Abstract

Endovascular embolization can selectively deploy embolic agents into diseased or injured blood vessels to complete the treatment. However, traditional embolic agents still face challenges, such as poor intravascular diffusivity, non‐biodegradable, unstable mechanical properties, radiolucency, and recanalization. Herein, we report a poly (lipoic acid‐tannic acid)/tromethamine/Galinstan (PLTTG) dimethyl sulfoxide (DMSO) solution‐derived hydrogel liquid embolic agent. By injecting PLTTG DMSO solution into body fluids, a PLTTG hydrogel can be formed in situ owing to the solvent exchange induced intra‐ and inter‐polymer hydrogen bonding and electrostatic interactions. Moreover, the gelation time and injection forces of the solution as well as the mechanical properties and embolic pressure of the obtained hydrogels can be adjusted by changing the concentration of PLTTG. The PLTTG hydrogel can effectively embolize the renal artery and femoral vein without recanalization and displacement in rabbit models. Furthermore, the hydrogel can embolize the ruptured femoral artery to arrest active bleeding. Owing to the advantages of the hydrogel, including adjustable gelation time, mechanical properties, viscosities, injection forces, and embolic pressure, as well as good biocompatibility and biodegradability, radiopacity, excellent embolization performance and intravascular diffusivity, easy usage, low cost, allowing it to be a potential embolic agent to treat multiple vascular diseases in clinic.

Construction of an Injectable Composite Double-Network Hydrogel as a Liquid Embolic Agent

“…Especially at 8 weeks, the left kidney atrophy was accompanied by a compensatory increase in the right kidney in the animals, particularly for those dosed by the highconcentration hydrogel, after which the residue weight of the kidney in the embolized side is less than 20 wt % (Figure S10), considered to be a significant shrinkage. 31,59,60 These results demonstrated that the CDN hydrogel remained stable in the left kidney without any migration and fragmentation and indicated that the renal artery and its branches can be effectively embolized without recanalization. Histopathological examination of the kidney resected from the embolized side shows that the renal cortex gradually shrank and thinned after embolization.…”

“…The low-concentration group was dominated by marginal atrophy, and the high-concentration group had a larger range of lesions. Especially at 8 weeks, the left kidney atrophy was accompanied by a compensatory increase in the right kidney in the animals, particularly for those dosed by the high-concentration hydrogel, after which the residue weight of the kidney in the embolized side is less than 20 wt % (Figure S10), considered to be a significant shrinkage. ,, These results demonstrated that the CDN hydrogel remained stable in the left kidney without any migration and fragmentation and indicated that the renal artery and its branches can be effectively embolized without recanalization.…”

“…30 Shan and co-workers utilized solvent exchange procedure to inject the mixture of poly(lipoic acid-tannic acid), tromethamine, and gallium indium tin alloy (PLTTG) in DMSO to allow the gelation of PLTTG by phase separation in aqueous medium to achieve the embolization. 31 Gong and coworkers synthesized an alginate-based injectable hydrogel which was cross-linked through in situ covalent bonding, i.e., thiol-Michael addition, together with calcium ion coordination, to effectuate femoral artery embolization on a rabbit model under physiological condition. 32 Therefore, hydrogel embolic agents have provided new possibilities for endovascular embolization surgery.…”

“…For example, Liu and co-workers used liquid metal–sodium alginate mixture solution and calcium chloride solution to inject into blood vessels by two catheters separately for a localized gelation reaction in the auricular vein to embolize rabbit auricular tumor . Shan and co-workers utilized solvent exchange procedure to inject the mixture of poly­(lipoic acid-tannic acid), tromethamine, and gallium indium tin alloy (PLTTG) in DMSO to allow the gelation of PLTTG by phase separation in aqueous medium to achieve the embolization . Gong and co-workers synthesized an alginate-based injectable hydrogel which was cross-linked through in situ covalent bonding, i.e., thiol-Michael addition, together with calcium ion coordination, to effectuate femoral artery embolization on a rabbit model under physiological condition .…”

Functional hydrogels for hepatocellular carcinoma: therapy, imaging, and in vitro model

“…Hydrogels with “liquid–solid” conversion function successfully integrate the advantages of solid and liquid embolic agents and avoid its defects, and have become one of the new hotspots in the treatment of tumors in recent years. Hydrogels are an ideal embolic agent for tumor interventional therapy owing to its adjustable viscosity, mechanical properties, gelation time, injection force and embolic pressure, good biocompatibility and biodegradability, and impermeable X-ray line, as well as excellent embolization performance and intravascular diffusivity [ 35 ]. Generally, hydrogels are polymer materials that are prepared by physical or chemical cross-linking using synthetic or natural polymers, which are extremely hydrophilic gels with three-dimensional network structures [ 36 , 37 ].…”