# Hydrogel-Based Therapeutic Strategies for Post-Cholecystectomy NAFLD: Targeting Bile Acid Signaling, Gut Microbiota, Inflammation, and Hepatic Fibrosis

## TL;DR

This review explores how hydrogels can treat liver disease after gallbladder removal by targeting bile acids, gut bacteria, inflammation, and liver scarring.

## Contribution

The paper introduces hydrogel-based strategies as a novel, targeted approach for post-cholecystectomy NAFLD.

## Key findings

- Hydrogels can sequester bile acids and deliver probiotics to restore gut-liver axis balance.
- Functional hydrogels reduce inflammation and fibrosis with localized, controlled drug release.
- Design principles for hydrogels include pH/redox/enzyme responsiveness and mucoadhesion.

## Abstract

Post-cholecystectomy non-alcoholic fatty liver disease (NAFLD), now encompassed within metabolic dysfunction-associated steatotic liver disease (MASLD), is increasingly linked to persistent disruption of bile acid kinetics and gut–liver axis signaling after gallbladder removal. Continuous bile delivery to the intestine reshapes the bile acid pool, perturbs FXR–FGF19/TGR5 pathways, remodels gut microbiota, and compromises epithelial barrier integrity, collectively promoting portal endotoxemia, chronic hepatic inflammation, and fibrogenic remodeling. Hydrogel-based biomaterials offer a mechanistically aligned therapeutic platform for this setting because they enable localized, sustained, and stimuli-responsive interventions at intestinal or hepatic sites. Functional hydrogels can sequester excess bile acids, protect and deliver probiotics/prebiotics/postbiotics, reinforce mucosal barrier function, and provide controlled release of anti-inflammatory or antifibrotic agents with reduced systemic exposure. In this review, we map emerging hydrogel strategies relevant to post-cholecystectomy NAFLD across four pathogenic nodes, bile acid dysregulation, dysbiosis, inflammation, and fibrosis, and highlight design principles (polymer chemistry, charge/hydrophobicity balance, mucoadhesion, and pH/redox/enzyme responsiveness) that enable targeted modulation of the gut–liver axis. Finally, we identify key translational gaps, including the lack of post-cholecystectomy-specific experimental models and standardized outcome measures integrating bile acid profiling, microbiome readouts, and hepatic histology. Hydrogel technologies represent a promising route toward localized and multimodal therapy in metabolic liver disease, warranting focused preclinical validation and clinical development.