{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T02:26:32Z","timestamp":1790130392038,"version":"4.0.1"},"reference-count":121,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,2,20]],"date-time":"2026-02-20T00:00:00Z","timestamp":1771545600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"University of Medicine and Pharmacy of Craiova"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Gels"],"abstract":"<jats:p>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\u2013liver axis signaling after gallbladder removal. Continuous bile delivery to the intestine reshapes the bile acid pool, perturbs FXR\u2013FGF19\/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\u2013liver 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.<\/jats:p>","DOI":"10.3390\/gels12020179","type":"journal-article","created":{"date-parts":[[2026,2,20]],"date-time":"2026-02-20T10:32:37Z","timestamp":1771583557000},"page":"179","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Hydrogel-Based Therapeutic Strategies for Post-Cholecystectomy NAFLD: Targeting Bile Acid Signaling, Gut Microbiota, Inflammation, and Hepatic Fibrosis"],"prefix":"10.3390","volume":"12","author":[{"given":"Georgiana-Andreea","family":"Marinescu","sequence":"first","affiliation":[{"name":"Department of Surgery, \u201cDr. \u0218tefan Odobleja\u201d Military Emergency Clinical Hospital, 200749 Craiova, Romania"},{"name":"Doctoral School, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3070-2858","authenticated-orcid":false,"given":"Alexandra-Daniela","family":"Rotaru-Zavaleanu","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, University of Medicine and Pharmacy of Craiova, 2\u20134 Petru Rares Street, 200349 Craiova, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emil-Tiberius","family":"Trasca","sequence":"additional","affiliation":[{"name":"Department of Surgery, \u201cDr. \u0218tefan Odobleja\u201d Military Emergency Clinical Hospital, 200749 Craiova, Romania"},{"name":"General Surgery Department, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena-Irina","family":"Caluianu","sequence":"additional","affiliation":[{"name":"Department of Surgery, \u201cDr. \u0218tefan Odobleja\u201d Military Emergency Clinical Hospital, 200749 Craiova, Romania"},{"name":"General Surgery Department, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oana","family":"Taisescu","sequence":"additional","affiliation":[{"name":"Department of Human Anatomy, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrei","family":"Gresita","sequence":"additional","affiliation":[{"name":"Department of Physiology, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Madalina Iuliana","family":"Musat","sequence":"additional","affiliation":[{"name":"Department of Scientific Research Methodology, University of Medicine and Pharmacy of Craiova, 2\u20134 Petru Rares Street, 200349 Craiova, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-3990-6483","authenticated-orcid":false,"given":"Dumitru","family":"Radulescu","sequence":"additional","affiliation":[{"name":"Department of Surgery, \u201cDr. \u0218tefan Odobleja\u201d Military Emergency Clinical Hospital, 200749 Craiova, Romania"},{"name":"General Surgery Department, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Razvan","family":"Mercut","sequence":"additional","affiliation":[{"name":"Department of Plastic and Reconstructive Surgery, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Citto-Iulian","family":"Taisescu","sequence":"additional","affiliation":[{"name":"Department of Physiology, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"158","DOI":"10.4254\/wjh.v14.i1.158","article-title":"Redefining non-alcoholic fatty liver disease to metabolic associated fatty liver disease: Is this plausible?","volume":"14","author":"Devi","year":"2022","journal-title":"World J. 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