Engineering carboxymethyl chitosan/dialdehyde starch hydrogel as a therapeutic platform for immuno-microbial modulation in ulcerative colitis.

The CMCS/DAS hydrogel was successfully engineered via dynamic Schiff base cross-linking between carboxymethyl chitosan and dialdehyde starch.

• Cross-linking occurs between aldehyde groups of dialdehyde starch (DAS) and amine groups of carboxymethyl chitosan (CMCS) to form dynamic imine bonds.
• The dynamic covalent Schiff base bonds confer self-healing properties to the hydrogel.
• The hydrogel is injectable, allowing for minimally invasive administration.

The CMCS/DAS hydrogel demonstrated excellent biocompatibility, robust tissue adhesion, and mechanical resilience.

• These physicochemical properties were considered crucial for ensuring sustained DEX release and reliable retention in the dynamic colonic environment.
• Self-healing capability was confirmed, allowing the hydrogel to recover after mechanical disruption.
• Tissue adhesion was characterized as 'robust,' supporting retention at inflamed mucosal sites.

The DEX-loaded hydrogel demonstrated pronounced immunomodulatory efficacy through promotion of macrophage polarization in vitro.

• The hydrogel promoted macrophage polarization, indicative of a shift from pro-inflammatory (M1) to anti-inflammatory (M2) phenotype.
• In vitro experiments were used to characterize the immunomodulatory mechanism.
• Dexamethasone (DEX) was the active anti-inflammatory agent loaded within the hydrogel matrix for localized delivery.

In a TNBS-induced rat model of UC, hydrogel treatment significantly attenuated inflammation compared to controls.

• The colitis model was established using trinitrobenzenesulfonic acid (TNBS) in rats.
• Treatment with the DEX-loaded CMCS/DAS hydrogel significantly reduced inflammatory markers at the colonic site.
• Localized delivery via the hydrogel platform was intended to reduce systemic toxicity associated with conventional DEX administration.

Hydrogel treatment promoted epithelial integrity and barrier repair in the TNBS-induced UC rat model.

• The hydrogel treatment restored mucosal barrier function, which is a central pathological feature of UC.
• Epithelial integrity was assessed histologically in colonic tissue sections from treated rats.
• Barrier repair was described as a key therapeutic outcome distinguishing this platform from current therapies.

Hydrogel treatment effectively rebalanced gut microbiota composition by enriching beneficial commensals in the TNBS-induced UC model.

• Gut microbiota dysbiosis was addressed as one of the central pathological processes of UC targeted by this platform.
• Treatment led to enrichment of beneficial commensal bacteria.
• Microbiota rebalancing was identified as a multifunctional therapeutic effect alongside anti-inflammatory and barrier-repair actions.

Current therapies for ulcerative colitis are limited by systemic toxicity, poor retention at inflamed sites, and insufficient promotion of mucosal healing.

• UC is characterized by mucosal barrier disruption, dysregulated immune activation, and microbial dysbiosis.
• These limitations motivated the development of a localized, mucoadhesive hydrogel delivery system.
• The CMCS/DAS hydrogel was designed specifically to overcome poor retention and localize therapeutic action.