Injectable and thermosensitive hydrogels mediating a universal macromolecular contrast agent with radiopacity for noninvasive imaging of deep tissues

Abstract

It is very challenging to visualize implantable medical devices made of biodegradable polymers in deep tissues. Herein, we designed a novel macromolecular contrast agent with ultrahigh radiopacity (iodinate content > 50%) via polymerizing an iodinated trimethylene carbonate monomer into the two ends of poly(ethylene glycol) (PEG). A set of thermosensitive and biodegradable polyester-PEG-polyester triblock copolymers with varied polyester compositions synthesized by us, which were soluble in water at room temperature and could spontaneously form hydrogels at body temperature, were selected as the demonstration materials. The addition of macromolecular contrast agent did not obviously compromise the injectability and thermogelation properties of polymeric hydrogels, but conferred them with excellent X-ray opacity, enabling visualization of the hydrogels at clinically relevant depths through X-ray fluoroscopy or Micro-CT. In a mouse model, the 3D morphology of the radiopaque hydrogels after injection into different target sites was visible using Micro-CT imaging, and their injection volume could be accurately obtained. Furthermore, the subcutaneous degradation process of a radiopaque hydrogel could be non-invasively monitored in a real-time and quantitative manner. In particular, the corrected degradation curve based on Micro-CT imaging well matched with the degradation profile of virgin polymer hydrogel determined by the gravimetric method. These findings indicate that the macromolecular contrast agent has good universality for the construction of various radiopaque polymer hydrogels, and can nondestructively trace and quantify their degradation in vivo . Meanwhile, the present methodology developed by us affords a platform technology for deep tissue imaging of polymeric materials.

In vivo near-infrared fluorescent fibrin highlights growth of nerve during regeneration across a nerve gap

“…An ideal bio-interactive contrast agent-carrying material, whether used for fluorescence or magnetic resonance imaging, would be controllably gelating, have high contrast agent labeling density, and behave (e.g., degrade) like it does when formulated without contrast agent. 29 Improved non-invasive imaging of major peripheral nerves in living subjects via dual-function imageable/regenerative tissue-engineered constructs will enable detailed post-operative monitoring. This could facilitate investigation of the role of specific ECM molecules during regeneration as well as evaluation of artificial nerve grafts, ultimately driving the formulation of customized artificial nerve grafts that induce autograft-like tissue regrowth.…”

Easily-injectable shear-thinning hydrogel provides long-lasting submucosal barrier for gastrointestinal endoscopic surgery

“…For example, the hydrogels formed by two or more components are inconvenient to be simultaneously injected [ 5 , 32 , 33 ], and photocurable hydrogels require ultraviolet light sources, making the operation difficult under the endoscope [ [34] , [35] , [36] , [37] ]. What's worse, the temperature-sensitive hydrogels have the risk of clogging [ [38] , [39] , [40] , [41] , [42] ]. Recently, few studies began to focus on the ex vivo barrier function of shear-thinning materials, but their biocompatibility and operability of endoscope are still unknown [ 6 , 43 ].…”

The Thermogel Chronicle─From Rational Design of Thermogelling Copolymers to Advanced Thermogel Applications

“…Professor Byeongmoon Jeong’s early work in understanding the gelation mechanism of the triblock copolymers as well as the subsequent work with cells influenced our group’s ideas on synthesis and tissue engineering applications . Besides the great efforts in potential medical application of thermogels, , Professor Jiandong Ding’s work provided valuable insights on the physical gelation mechanisms of thermogels by establishing the structure model of percolated micelle network, the underlying principle of molecular engineering of polymers and the new strategy of thermogels with significantly broad composition windows . Through his innovative thinking process, we could understand more about how our polymers behaved and how they can be tuned for future applications.…”