Anhui University of Science and Technology, Huainan, China.
Digestive Endoscopy Center, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China; Department of Gastroenterology, Changhai Hospital, Second Military Medical University (Naval Medical University), Shanghai, China.
Colloids Surf B Biointerfaces. 2023 Jun;226:113321. doi: 10.1016/j.colsurfb.2023.113321. Epub 2023 Apr 28.
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-β/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.
内镜黏膜下剥离术（ESD）是治疗早期食管癌和癌前病变的一种公认方法，但切除大面积的黏膜区域往往会导致术后食管狭窄。生物材料为治疗 ESD 后溃疡提供了一种新的选择。在这项研究中，我们开发了一种定义明确的氨解基四臂聚乙二醇（Tetra-PEG）水凝胶，并在猪模型中研究了其预防食管 ESD 诱导狭窄的疗效和相关机制。就材料特性而言，Tetra-PEG 水凝胶具有良好的生物相容性、高保湿能力、强组织黏附性和高机械强度。然后，将 6 只国产雌性猪随机分为 PEG（n=3）和对照组（n=3）。所有猪均进行 3/4 周食管周长 ESD。在 PEG 组，Tetra-PEG 水凝胶通过内镜轻松输送，并紧密贴合溃疡床。与对照组相比，Tetra-PEG 水凝胶通过调节 TGF-β/Smad2 信号通路，加速早期食管溃疡愈合，促进上皮再生，减轻炎症和纤维化，从而减轻纤维化狭窄的形成。综上所述，我们的研究结果表明，Tetra-PEG 水凝胶是一种有前途和有吸引力的候选药物，可用于预防食管 ESD 诱导的溃疡修复过程中纤维化狭窄的形成。
