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Fig 1.

Mussel adhesive proteins and mussel-inspired chitosan-catechol hemostatic agent.

(A) The coexistence of catechol (DOPA) and amine (lysine) groups in mussel adhesive proteins found in mussel threads is crucial for its underwater adhesion. (B) Synthesis and chemical structure of CHI-C. (C) UV-vis spectrum of the CHI-C solution. (D) 1H-NMR spectrum of CHI-C dissolved in D2O. (E) Mussel-inspired hemostatic agent (CHI-C) developed by chemically conjugating catechol groups to amine-rich chitosan, and (F) an endoscopic photograph of the CHI-C hemostatic agent applied to gastric ulcer bleeding.

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Fig 2.

Study design of EMR-induced GI bleeding in a heparinized pig model.

(A) A schematic diagram of the overall experimental procedure, including animal preparation, endoscopic procedure for hemostatic effect evaluation, and follow-up study for short-term safety evaluation. (B) EMR-C technique in a pig’s stomach. (C) aPTT values before (baseline) and after heparin injection. Data were analyzed using a paired t-test. aPTT, activated partial thromboplastin time; inj., injection; ****, p < 0.0001.

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Fig 3.

Initial (2 min) hemostatic effects.

(A) Representative photographic images of the application of each test material (upper panel) and hemostatic status at 2 min after the application (lower panel). (B) Initial hemostasis achievement (%) at 2 min after the application. Data were analyzed using the Mann-Whitney U test. ****, p < 0.0001; ns, statistically non-significant.

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Table 1.

Scoring and stage classification of gastric ulcer according to Sakita-Miwa classification.

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Table 1 Expand

Fig 4.

Rebleeding rate and ulcer healing activity (endoscopic observation).

(A) Rebleeding rate (%) on Days 1, 5, and 10. Data were analyzed using the Fisher’s exact test. (B) Representative endoscopic images for the rebleeding and ulcer healing on Days 1, 5, and 10 (red arrow: re-bleeding, blue arrow: necrotic tissue). (C) Healing scores on Days 1, 5, and 10 by endoscopic observation. Data were analyzed by a repeated measures one-way ANOVA using a mixed-effects model with the missing data. (D and E) Representative photographs of ulcers after the autopsy on Day 10. (D) no-treatment group. (E) CHI-C group. ****, p < 0.0001; ns, non-significant.

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Fig 5.

Histological analysis.

(A) Representative microscopic images on Days 1, 5, and 10 (red arrow: granulation tissue, blue arrow: re-epithelialized layer, asterisk: inflammation in muscular propria). (B) Relative healing area (%) compared to the no-treatment group. (C−E) Ulcer depth on Days 1, 5, and 10. (F−H) Inflammation levels of each group on Days 1, 5, and 10.

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