Non-invasive monitoring of in vivo degradation of a radiopaque thermoreversible hydrogel and its efficacy in preventing post-operative adhesions

Abstract

In vivo behavior of hydrogel-based biomaterials is very important for rational design of hydrogels for various biomedical applications. Herein, we developed a facile method for in situ fabrication of radiopaque hydrogel. An iodinated functional diblock copolymer of poly(ethylene glycol) and aliphatic polyester was first synthesized by coupling the hydroxyl end of the diblock copolymer with 2,3,5-triiodobenzoic acid (TIB) and then a radiopaque thermoreversible hydrogel was obtained by mixing it with the virgin diblock copolymer. A concentrated aqueous solution of the copolymer blend was injectable at room temperature and spontaneously turned into an in situ hydrogel at body temperature after injection. The introduction of TIB moieties affords the capacity of X-ray opacity, enabling in vivo visualization of the hydrogel using Micro-CT. A rat model with cecum and abdominal defects was utilized to evaluate the efficacy of the radiopaque hydrogel in the prevention of post-operative adhesions, and a significant reduction of the post-operative adhesion formation was confirmed. Meanwhile, the maintenance of the radiopaque hydrogel in the abdomen after administration was non-destructively detected via Micro-CT scanning. The reconstructed three-dimensional images showed that the radiopaque hydrogel with an irregular morphology was located on the injured abdominal wall. The time-dependent profile of the volume of the radiopaque hydrogel determined by Micro-CT imaging was well consistent with the trend obtained from the dissection observation. Therefore, the radiopaque thermoreversible hydrogel can serve as a potential visualized biomedical implant and this practical mixing approach is also useful for further extension into the in vivo monitoring of other biomaterials.

Statement of significance: While a variety of biomaterials have been extensively studied, it is rare to monitor in vivo degradation and medical efficacy of a material after being implanted deeply into the body. Herein, the radiopaque thermoreversible hydrogel developed by us not only holds desirable performance on the prevention of post-operative abdominal adhesions, but also allows non-invasive monitoring of its in vivo degradation with CT imaging in a real-time, quantitative and three-dimensional manner. The methodology based on CT imaging provides important insights into the in vivo fate of the hydrogel after being deeply implanted into mammals for different biomedical applications and significantly reduces the amount of animals sacrificed.

Keywords: In vivo degradation; Micro-CT imaging; Post-operative adhesions; Radiopaque hydrogel; Sol-gel transition.