Hydrogel Derived from Decellularized Porcine Small Intestinal Submucosa as a Physical Shielding Repaired the Gut Epithelial Barrier of Murine Ulcerative Colitis

Abstract

Ulcerative colitis (UC) is associated with the shedding of the gut mucus. Decellularized porcine small intestinal submucosa (SIS-ECM) contains numerous active forms of extracellular matrix as well as growth factors. Herein, a mucus-mimetic hydrogel (MAG) is designed as a barrier therapy by integrating SIS-ECM with hyaluronic acid and epigallocatechin-3-gallate. MAG not only presented the viscoelastic behaviors with G' of 4000 Pa but also good thixotropy. Moreover, MAG as a physical shielding is effective to hinder E. coli invasion. Besides, the good repairing effect on the injured Caco-2 cells is presented by MAG. When MAG as a biomimetic mucus is rectally administrated to colitis mouse, it alleviated effectively the colitis symptoms and improved the colonic shorting. Moreover, expression of IL-1β, IL-6, and TNF-α at the laminae propria is substantially inhibited by MAG. Besides, the colonic epitheliums are well rearranged, and the tight junction proteins (ZO-1, Occludin-1, Claudin-5) between them are greatly upregulated after MAG treatment. Meanwhile, the mucus secretion of goblets cells is effectively repaired by MAG treatment. The repairing mechanism of intestinal mucosa barriers is associated with promoting the proliferation and differentiation of intestinal stem cells. Collectively, MAG might be a promising strategy of barrier therapy for UC.