Novel temperature-responsive, biodegradable and injectable collagen sol for the endoscopic closure of colonic perforation holes: Animal study (with videos)

Objectives: Endoscopic submucosal dissection (ESD) poses a risk of intraprocedural perforation. We have developed a biodegradable injectable collagen sol that undergoes a liquid-to-gel formation in response to body temperature. Here, we investigated the feasibility of this novel collagen sol for the endoscopic closure of iatrogenic perforation holes. Methods: In two experiments, 12 and 5 colonic perforation holes (3–5 mm) were made using an ESD knife in four and three live pigs under general anesthesia, respectively. In Experiment 1, collagen sol was delivered to the perforation holes using an endoscopic catheter. When the colon was expanded by CO₂ insufflation, endo-clips were applied to the perforation holes. For Experiment 2, Collagen sol adjusted based on the Experiment 1 results was delivered to the perforation holes in the same manner. A leak test was performed for every colon after the pigs were killed, and the histology of the perforation sites was evaluated. Results: In both experiments, collagen sol was smoothly delivered to the target area and fixed as a gel on the perforation holes. Experiment 1, 83% (10/12) of the perforation holes were completely closed, and all endo-clips were placed with composure. Experiment 2, all perforation holes were completely closed with collagen gel. There was no leak from the perforation holes. Histology revealed a fixation of the collagen gel as an embolus agent in the perforation holes. Conclusions: This novel collagen sol may be used for the endoscopic closure of intraprocedural perforation. Further studies will determine this collagen sol's clinical feasibility and safety.