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

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Bioactive Materials 2021年第12期6卷 4717-4728页

作者： Xiaohui Wu Xin Wang Xiaobin Chen Xiaowei Yang Qian Ma Guohua Xu Lin Yu Jiandong Ding State Key Laboratory of Molecular Engineering of Polymers Department of Macromolecular ScienceShanghai Stomatological HospitalFudan UniversityShanghai200438China Department of Orthopedic Surgery Spine CenterChangzheng HospitalNaval Medical UniversityShanghai200003China Zhuhai Fudan Innovation Institute ZhuhaiGuangdong519000China

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.

关键词： Thermosensitive hydrogels Radiopacity Block copolymers In vivo degradation non-invasive deep tissue imaging

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