Introduction: Endoscopic mucosal resection(EMR)and endoscopic submucosal dissection (ESD) can remove large gastrointestinal (GI) tumors but increase the risk of delayed bleeding. Here we demonstrate the development of a novel hydrogel containing epinephrine nanoparticles that can be injected for sub-mucosal lift and for topical application as a bioadhesive for post-resection bleeding prevention and control.
Methods: A novel biocompatible, degradable hydrogel polymer containing epinephrine nanoparticles was developed. Hydrogels were injected into the porcine stomach to confirm the feasibility of submucosal lifting, and necropsy performed after 14 days for histopathological evaluation. A bleeding animal model was created by administering aspirin, clopidogrel, and intravenous heparin to 6 pigs. Gastric, colonic ESD was performed in 3 pigs each to create 3-5 cm bleeding ulcers using our hydrogel for submucosal lifting. Our hydrogel was then applied to the surface of the bleeding ulcer, followed by an activator that creates cross-linking of hydrogel to solidify the hydrogel instantly for ultrafast gelation. A sham ESD was created in each pig for comparison. Necropsy was performed after 48 hours to evaluate the presence of bioadhesive hydrogel at the ulcer site.
Results: Our hydrogel demonstrates reverse thermal gelation, i.e., the viscosity increased from room temperature to body temperature, allowing easy delivery through the injection needle while significantly increasing retention of the submucosal injection when compared to other lifting products. Epinephrine nanoparticles allowed a sustained release of epinephrine for up to 72 hours in comparison with regular epinephrine. In vivo injection of the gel in the porcine stomach and histopathological examination of the injection site confirmed complete degradation of the injected hydrogel polymers without significant inflammation or granuloma formation. Durable hemostasis was achieved in all gastric, colonic ESD ulcer sites (6/6) compared to none in the control groups (p=0.002) (figures 1A-D). Examination of the ulcer site after 48 hours confirmed intact gel retention (figure 1E) and histopathology confirmed improved healing compared to control ulcer sites.
Discussion: The use of our novel epinephrine nanoparticle-containing hydrogel that can be injected for submucosal lifting and applied as bioadhesive is expected to prevent and control GI bleeding while promoting healing, and facilitating endoscopic resection procedures.
. A0288 - POSTER WITHDRAWN, ACG 2022 Annual Scientific Meeting Abstracts. Charlotte, NC: American College of Gastroenterology.