Growth Factors-Loaded Temperature-Sensitive Hydrogel as Biomimetic Mucus Attenuated Murine Ulcerative Colitis via Repairing the Mucosal Barriers.
Li. Dingwei D; Shangguan. Jianxun J; Yu. Fengnan F; Lin. Gaolong G; Pan. Hanxiao H; Zhang. Mengjiao M; Lin. Haoran H; Chen. Ben B; Xu. Helin H; Hu. Sunkuan S
Key Findings
- The hydrogel solidifies within 10 seconds at body temperature and adheres specifically to inflamed colon tissue
- KPV‑containing hydrogel reduced weight loss, disease activity index, and pro‑inflammatory cytokines in colitis‑affected rats
- Tight‑junction proteins (Zonula‑1 and Claudin‑5) were up‑regulated, indicating improved gut barrier function
Practical Outcomes
- For now, the work shows that delivering KPV via a mucus‑mimicking gel can help heal ulcerative colitis in animal models, but it isn’t a protocol you can apply yourself. It suggests future possibilities for targeted gut therapies, yet human safety and dosing data are still needed.
Summary
Researchers made a gel that turns solid at body temperature and sticks to inflamed colon tissue. When they put this gel, which contains a tiny anti‑inflammatory peptide called KPV, into rats with ulcerative colitis, the animals lost less weight, had lower disease scores, and showed reduced gut inflammation and better gut lining integrity. The study is still in animals, so it’s not a ready‑to‑use treatment for people yet.
Abstract
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 <i>Escherichia coli</i>. 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.
Study Information
pubmed
2024
2024-01-30T00:00:00.000Z
10.1021/acsami.3c15684
17
46