A novel tetra-PEG based hydrogel for prevention of esophageal stricture after ESD in a porcine model

Endoscopic submucosal dissection (ESD) is an accepted treatment for early esophageal cancer and precancerous lesions, but resection of a large mucosal area often leads to postoperative esophageal stricture. Biomaterials provide a new option for the treatment of post-ESD ulcers. In this study, we developed a well-defined ammonolysis-based tetra-armed poly (ethylene glycol) (Tetra-PEG) hydrogel and investigated its efficacy and related mechanisms for preventing esophageal ESD-induced stricture in a porcine model. In terms of material properties, Tetra-PEG hydrogel present great biocompatibility,great capability to retain moisture, strong tissue adhesion and high mechanical strength. Then, six domestic female pigs were randomly divided into PEG (n = 3) and control groups (n = 3). A 3/4 of the esophageal circumference ESD was performed in all pigs. In PEG group, Tetra-PEG hydrogel was easily delivered via endoscopy and adhered to the ulcer bed tightly. Compared to control group, Tetra-PEG hydrogel accelerated esophageal ulcer healing at an early stage with enhanced epithelium regeneration, milder inflammation and lesser fibrosis by regulating TGF-& beta;/Smad2 signaling. Taken together, our findings reveal Tetra-PEG hydrogel is a promising and attractive candidate for preventing the formation of fibrotic stricture in the process of esophageal ESD-induced ulcer repair.

Automated summary

Endoscopic submucosal dissection (ESD) is an effective treatment for early esophageal cancer and precancerous lesions, but it often leads to postoperative esophageal stricture. This study developed a tetra-armed poly(ethylene glycol) (Tetra-PEG) hydrogel and demonstrated its efficacy in preventing ESD-induced stricture in a porcine model. The Tetra-PEG hydrogel exhibited great biocompatibility, moisture retention, tissue adhesion, and mechanical strength. Compared to the control group, the Tetra-PEG hydrogel promoted early esophageal ulcer healing by enhancing epithelium regeneration, reducing inflammation, and fibrosis through the TGF-β/Smad2 signaling pathway.