Endoscopic application of mussel-inspired phenolic chitosan as a hemostatic agent for gastrointestinal bleeding: A preclinical study in a heparinized pig model

Abstract

Marine mussels secrete adhesive proteins to attach to solid surfaces. These proteins contain phenolic and basic amino acids exhibiting wet adhesion properties. This study used a mussel-inspired hemostatic polymer, chitosan-catechol, to treat gastrointestinal bleeding caused by endoscopic mucosal resection in a heparinized porcine model. We aimed to evaluate the hemostatic efficacy and short-term safety of this wet adhesive chitosan-catechol. We used 15 heparinized pigs. Four iatrogenic bleeding ulcers classified as Forrest Ib were created in each pig using an endoscopic mucosal resection method. One ulcer in each pig was untreated as a negative control (no-treatment group). The other three ulcers were treated with gauze (gauze group), argon plasma coagulation (APC group), and chitosan-catechol hemostatic agent (CHI-C group) each. The pigs were sacrificed on Days 1, 5, and 10, and histological examination was performed (n = 5 per day). Rapid hemostasis observed at 2 min after bleeding was 93.3% (14/15) in the CHI-C group, 6.7% (1/15) in the no-treatment group, 13.3% (2/15) in the gauze group, and 86.7% (13/15) in the APC group. No re-bleeding was observed in the CHI-C group during the entire study period. However, a few re-bleeding cases were observed on Day 1 in the no-treatment, gauze, and APC groups and on Day 5 in the gauze and APC groups. On histological analysis, the CHI-C group showed the best tissue healing among the four test groups. Considering the results, chitosan-catechol is an effective hemostatic material with reduced re-bleeding and improved healing.