Liu Shuang, Luan Zhaohui, Wang Tongchuan, Xu Kaige, Luo Qiang, Ye Shaosong, Wang Wei, Dan Ruijue, Shu Zhenzhen, Huang Yu, Mequanint Kibret, Fan Chaoqiang, Xing Malcolm, Yang Shiming
Department of Gastroenterology, Xinqiao Hospital, Army Medical University, No.183, Xinqiao Street, Shapingba District, Chongqing400037, China.
Departments of Mechanical Engineering, University of Manitoba, Winnipeg, ManitobaR3T 2N2, Canada.
ACS Nano. 2023 Jan 10;17(1):111-126. doi: 10.1021/acsnano.2c05247. Epub 2022 Nov 7.
Gastrointestinal tract perforation is a full-thickness injury that causes bleeding and fatal infection of the peritoneum. This condition worsens in an acidic gastric environment which interferes with the normal coagulation cascade. Current endoscopic clips to repair gastric perforations are ineffective, and metal or plastic occluders need secondary surgery to remove them. Herein, we report a self-expandable, endoscopy deliverable, adhesive hydrogel to block gastric perforation. We found the nanosilica coating significantly enhanced the adhesive strength even under a simulated strong acidic stomach environment. The developed device was disulfide cross-linked for the reducible degraded gel. By loading with vonoprazan fumarate (VF) and acidic fibroblast growth factor (AFGF), the hyperboloid-shaped device can have a sustained drug release to regulate intragastric pH and promote wound healing. The gel device can be compressed and then expanded like a mushroom when applied in an acute gastric perforation model in both rabbits and minipigs. By utilizing a stomach capsule robot for remotely monitoring the pH and by immunohistochemical analysis, we demonstrated that the compressible hyperboloid-shaped gel could stably block the perforation and promoted wound healing during the 28 days of observation. The real-time pH meter demonstrated that the gel could control intragastric pH above 4 for nearly 60 h to prevent bleeding.
胃肠道穿孔是一种全层损伤，可导致出血和致命的腹膜感染。在酸性胃环境中，这种情况会恶化，因为酸性环境会干扰正常的凝血级联反应。目前用于修复胃穿孔的内镜夹效果不佳，金属或塑料封堵器需要二次手术才能取出。在此，我们报告了一种可通过内镜递送的自膨胀粘性水凝胶，用于封堵胃穿孔。我们发现，即使在模拟的强酸性胃环境下，纳米二氧化硅涂层也能显著提高粘附强度。所开发的装置通过二硫键交联形成可还原降解的凝胶。通过负载富马酸沃克索拉唑（VF）和酸性成纤维细胞生长因子（AFGF），这种双曲线形装置可以实现药物的持续释放，以调节胃内pH值并促进伤口愈合。在兔和小型猪的急性胃穿孔模型中应用时，这种凝胶装置可以被压缩，然后像蘑菇一样展开。通过利用胃胶囊机器人远程监测pH值，并通过免疫组织化学分析，我们证明了这种可压缩的双曲线形凝胶在28天的观察期内能够稳定地封堵穿孔并促进伤口愈合。实时pH计显示，这种凝胶可以将胃内pH值控制在4以上近60小时，以防止出血。
