Robust closure of post-endoscopic submucosal dissection perforation by microparticle-based wound dressing

Abstract Endoscopic submucosal dissection (ESD) has been used as a minimally invasive cancer treatment for early-stage gastrointestinal cancer. However, cancer dissection in thin tissues, such as the duodenum and large intestine, often cause post-ESD and delayed perforation, which elicit severe complications. In this study, we report a microparticle-based wound dressing with hydrophobically-modified gelatin that can close the perforation after ESD. Hydrophobized microparticles were prepared using a coacervation method in a water/ethanol mixed solvent. The optimized alkyl chain length and degree of substitution of hydrophobic groups improved the mechanical strength of the hydrogel formed by hydration and fusion of the microparticles. The hydrogels formed on tissue defects revealed higher burst strength in ex vitro perforation models using duodenum, large intestine, and stomach under wet conditions compared with hydrogels without hydrophobic modification. The particle fusion was determined to be a crucial step to yield a high burst strength. An in vivo degradability evaluation showed that microparticle hydrogels subcutaneously implanted in rats degraded within 14 days. The microparticle wound dressing is expected to be applicable to post-ESD perforation and prevent delayed perforation.