A thermoresponsive supramolecular copolymer hydrogel for the embolization of kidney arteries

Abstract

Our team has previously reported a high strength thermoplastic supramolecular polymer hydrogel. However, the hydrogel required injection temperatures outside the physiological range therefore preventing its use in a living environment. In this article, we reported a thermoresponsive supramolecular copolymer hydrogel p(N-acryloyl glycinamide-co-acrylamide) (PNAGA-PAAm), which can be injected at temperatures within the physiological range. We used rheological measurements to demonstrate that the transition temperature (upper critical solution temperature) of both the moduli and gel–sol could be finely adjusted by controlling both the ratio and concentration of the monomer. Adding iohexol (contrast agent) in PNAGA-PAAm hydrogels contributed to the decreased moduli and gel–sol transition temperature due to weakening of the hydrogen bonding interactions. The cytocompatible and hemocompatible PNAGA-PAAm sol mixed with iohexol was injected into the renal arteries of rabbits through a microcatheter at a temperature within the high biological range. The transition from the injection temperature (high biological range) to body temperature (basal for the animals) quickly solidified the embolic agent without the occurrence of dehydration, therefore overcoming the main limitation of LCST-typed poly(N-isopropylacrylamide) previously reported. Angiography and histological examination demonstrated the successful embolization of both renal arteries and no recanalization was observed after 8 weeks. The PNAGA-based supramolecular copolymer hydrogel is a novel embolic agent that allows for the occlusion of larger sized arteries in a biocompatible environment.