Smart Silk-Based In Situ Sol-Gel Modulates Rectal Microenvironment for Effective Ulcerative Colitis Alleviation

Area of Science:

• Biomaterials Science
• Gastroenterology
• Immunology

Background:

• Ulcerative colitis (UC) is a chronic inflammatory bowel disease linked to colorectal cancer.
• Current UC treatments focus on inflammation but overlook microenvironmental factors crucial for healing.
• Impaired mucosal healing and microenvironment dysregulation contribute to treatment failure in UC.

Purpose of the Study:

• To develop and evaluate a novel silk fibroin-based fucoidan (SFU) in situ rectal gel for UC treatment.
• To assess the antioxidant, anti-inflammatory, and mucosal healing properties of SFU in a preclinical UC model.

Main Methods:

• Rheological analysis confirmed SFU gel's sol-gel transition under physiological conditions.
• In vitro assessment of antioxidant activity (DPPH radical scavenging, ROS, NO inhibition).
• Evaluation of SFU efficacy in a dextran sodium sulfate (DSS)-induced UC mouse model, assessing clinical signs, inflammatory markers, macrophage polarization, and gut barrier integrity.

Main Results:

• SFU gel demonstrated significant antioxidant activity with a 73.3% DPPH radical scavenging rate.
• SFU treatment alleviated UC symptoms in mice, reducing weight loss and disease activity index (DAI).
• SFU therapy promoted M2 macrophage polarization, decreased IL-6 and TNF-α, enhanced tight junction proteins (Occludin-1, ZO-1), restored goblet cells and mucin, and prevented fibrosis.

Conclusions:

• SFU rectal gel is a promising therapeutic agent for ulcerative colitis.
• SFU exhibits potent antioxidant and anti-inflammatory effects, promoting gut mucosal healing and barrier restoration.
• SFU represents a potential natural therapy for UC, addressing microenvironmental factors for improved treatment outcomes.