posted on 2024-01-30, 15:05authored byDingwei Li, Jianxun Shangguan, Fengnan Yu, Gaolong Lin, Hanxiao Pan, Mengjiao Zhang, Haoran Lin, Ben Chen, Helin Xu, Sunkuan Hu
The
pathogenesis of ulcerative colitis (UC) is associated with
the shedding of the gut mucus. Herein, inspired by the biological
functions of mucus, growth factors-loaded in situ hydrogel (PHE-EK)
was designed for UC treatment by integrating dihydrocaffeic acid-modified
poloxamer as a thermosensitive material with hyaluronic acid (colitis-specific
adhesive), epigallocatechin-3-gallate (antibacterial agent), and bioactive
factors (KPV tripeptide and epidermal growth factor). PHE-EK presented
good thermosensitive properties, as a flowable liquid at room temperature
and gelled within 10 s when exposed to body temperature. PHE-EK hydrogel
presented good mechanical strength with a strain of 77.8%. Moreover,
PHE-EK hydrogel displayed antibacterial activity against Escherichia coli. Importantly, in vitro and in vivo
adhesive tests showed that the PHE-EK hydrogel could specifically
adhere to the inflamed colon via electrostatic interaction. When PHE-EK
as a biomimetic mucus was rectally administrated to colitis rats,
it effectively hindered the body weight loss, reduced the disease
activity index and improved the colonic shorting. Moreover, the expression
of pro-inflammatory cytokines (e.g., IL-1β, IL-6, and TNF-α)
at the laminae propria or epitheliums of the colon for colitis rats
was substantially inhibited by PHE-EK. Besides, the colonic epitheliums
were well rearranged, and the tight junction proteins (Zonula-1 and
Claudin-5) between them were greatly upregulated after PHE-EK treatment.
Collectively, PHE-EK might be a promising therapy for UC.