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

Abstract

Objectives: Endoscopic submucosal dissection (ESD) poses a risk of intraprocedural perforation. We have developed a biodegradable injectable collagen sol that undergoes a liquidto-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 CO 2 insufflation, endoclips 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.

Potential of temperature‐response collagen‐genipin sol as a novel submucosal injection agent for endoscopic resection: Acute and chronic phase study using living animals

“…The significant advantage of the PSC/Ge to other agents including what is commercialized in Western countries [12][13][14][15][16] is not only maintaining good mucosal lifting, but also that it exhibits potential for multiple clinical applications, as previously reported: closure of colonic perforation or treatment of gastrointestinal ulcers. 8,17,18 Although the PSC/Ge did not indicate healing of artificial ulcers more effectively than NS in this study, it has the possibility of preventing or reducing the risk of delayed adverse events. In addition, the PSC/Ge has the potential to be more useful for lesions with submucosal fibrosis than existing agents, as our previous report showed that it had a higher retention rate of mucosal lifting than hyaluronic acid.…”

Closure of gastric perforations during endoluminal resection using a novel biodegradable collagen sol: A feasibility survival study on porcine model (with video)

“…In our previous study, perforation models were only with surrounding intact mucosa using live porcine colon. 13 We plan on assessing whether this collagen sol would be similarly effective with larger perforations or perforations without exposed submucosa layer in a future study. Additionally, the location of the perforation site in the upper body along the greater curvature of the stomach may have contributed to the collagen sol not being displaced from the perforation because of its gravity dependent position.…”

“…In addition, the advantages of this collagen sol are the capacity to modulate its viscosity and cure rate, the temperature-responsiveness for gelation, and the gel strength (which are related to low diffusion rates, the closure of tissue defects, and tissue adhesiveness, respectively). We have been compounding various formulations of collagen sols for different purposes 13,14 including the collagen sol used in this study to close gastric perforations.…”

“…8,9 Recently, we developed an injectable, temperatureresponsive and biodegradable collagen sol that transforms from a liquid to a gel state in response to body temperature, and we considered the ability of this novel collagen sol as a sealant closure agent for management of perforation during ESD. [10][11][12] Although we have previously reported the feasibility of this collagen sol for the endoscopic closure of perforations in live porcine animal studies, 13 we used only porcine colons and there was no survival experiment to guide clinical use of the collagen sol. Therefore, we conducted the present porcine acute and survival experiments to determine the safety and efficacy of this novel collagen sol for endoscopic closure of perforation during endoscopic resection in the stomach.…”

Innovative sealant: Do you know the message of Gardenia flowers?

“…We read with great interest the article in Digestive Endoscopy entitled “Potential of temperature‐response collagen‐genipin sol as a novel submucosal injection agent for endoscopic resection: Acute and chronic phase study using living animals” by Takatori et al 5 . Previous studies conducted by their group showed the efficacy of a collagen‐genipin sol (CGS) as a sealant closure agent for minor perforations in the porcine stomach and colon 6–8 . This CGS maintains fluidity at room temperature as an injectable solution.…”