Injectable temperature-sensitive hydrogel facilitating endoscopic submucosal dissection

Ruifen Xu; Xiaoyu Yang; Tong Yi; Tao Tan; Zhongqi Li; Xuyang Feng; Jing Rao; Pinghong Zhou; Hao Hu; Yonghua Zhan

doi:10.3389/fbioe.2024.1395731

Injectable temperature-sensitive hydrogel facilitating endoscopic submucosal dissection

Front Bioeng Biotechnol. 2024 Apr 29:12:1395731. doi: 10.3389/fbioe.2024.1395731. eCollection 2024.

Authors

Ruifen Xu^#¹, Xiaoyu Yang^#², Tong Yi², Tao Tan^{3

4}, Zhongqi Li⁴, Xuyang Feng⁵, Jing Rao¹, Pinghong Zhou⁴, Hao Hu⁴, Yonghua Zhan²

Affiliations

¹ Anesthesiology Department, Shaanxi Provincial People's Hospital, Xi'an, Shaanxi, China.
² Engineering Research Center of Molecular and Neuro Imaging of the Ministry of Education, School of Life Science and Technology, Xidian University, Xi'an, Shaanxi, China.
³ University of Shanghai for Science and Technology, Shanghai, China.
⁴ Endoscopy Center and Endoscopy Research Institute, Shanghai Collaborative Innovation Center of Endoscopy, Zhongshan Hospital, Fudan University, Shanghai, China.
⁵ Department of Cardiology, Xijing Hospital, The Fourth Military Medical University, Xi'an, Shaanxi, China.

^# Contributed equally.

Abstract

Purpose: Early gastrointestinal tumors can be removed by endoscopic procedures. Endoscopic mucosal dissection (ESD) requires submucosal fluid injection to provide mucosal elevation and prevent intraoperative perforation. However, the clinically applied normal saline mucosal elevation height is low for a short time, which often requires multiple intraoperative injections that increase the inconvenience and procedure time. In addition, recently researched submucosal injection materials (SIM) suffer from complex preparation, poor economy, and poor biocompatibility. Therefore, there is an urgent need for a new type of SIM that can provide long, safe and effective mucosal elevation in support of the endoscopic procedures. Methods: The FS hydrogel is based on polyethylene-polypropylene glycol (F-127) mixed with sodium alginate (SA). The different physicochemical properties of FS hydrogels were characterized through various experiments. Afterward, various biosafety assessments were carried out. Finally, the performance of FS hydrogels was evaluated by in vitro submucosal injection and in vivo swine ESD. Results: The experimental results show that the FS hydrogel is liquid at room temperature, making it easy to inject, and when injected under the mucosa, it undergoes temperature-induced cross-linking, transforming from a liquid to a solid state to provide long-lasting mucosal augmentation. At the same time, the FS hydrogel exhibits controllable gelation, stability, and biocompatibility. The results of in vitro submucosal injections and in vivo ESD procedures showed that FS achieves high mucosal augmentation and provides good submucosal cushioning in the long term. Conclusion: In summary, the F-127/SA hydrogel is simple to synthesize, cost-effective, safe, easy to store, and able to assist ESD well from the perspective of practical clinical problems, indicating that the FS hydrogel can be an ideal potent submucosal injection substitution.

Keywords: endoscopic mucosal dissection; gastrointestinal tumors; hydrogel; mucosal elevation; submucosal injection.

Grants and funding

The author(s) declare that financial support was received for the research, authorship, and/or publication of this article. This work was supported, in part, by the Natural Science Basic Research Program of Shaanxi Province (No. 2023-JC-YB-658, 2024JC-ZDXM-47), and the Shanghai Municipal Science and Technology (22Y11907500, 23ZR1453100).