Bioactive shape-memory biodegradable biliary stent functionalized with dHAM-Curcumin for improved biliary repair and...

Anastomotic stricture after biliodigestive reconstruction remains a clinical challenge leading to recurrent cholangitis, jaundice, and secondary biliary cirrhosis. Conventional plastic stents provide temporary support but are prone to biofilm formation and biliary sludge accumulation and require secondary removal procedures. There is a need for biodegradable biliary stents that provide sufficient mechanical support while actively modulating the local microenvironment. A biodegradable shape-memory biliary stent composed of a poly(CL-co-TOSUO)/BaSO₄ (PCT/BaSO₄) composite core coated with a decellularized human amniotic membrane-curcumin (dHAM-Cur) hydrogel was developed. In vivo performance was assessed in rat subcutaneous and duodenal implantation models and in a rabbit orthotopic common bile duct stenting model. Gut microbiota and bile metabolomic changes were analyzed by 16S rRNA sequencing and untargeted Liquid Chromatography-Mass Spectrometry (LC-MS). The PCT/BaSO₄ stent exhibited suitable mechanical properties, radiopacity, and shape memory functionality, with a degradation profile that matched the expected biliary healing period. The dHAM-Cur coating increased surface hydrophilicity and supported sustained curcumin release. The functionalized stent reduced inflammatory cell infiltration, fibrous capsule formation, and bile duct fibrosis, and preserved biliary patency compared with plastic and PCL/BaSO₄ controls in vivo. Multi-omics analyses suggested that the stent subtly reshaped gut microbial composition and modulated bile acid-related metabolic pathways. The PCT/BaSO₄@dHAM-Cur composite demonstrated local anti-inflammatory and anti-adhesion effects in preclinical models, along with favorable biocompatibility and anti-restenotic potential. This system holds promise as a therapeutic platform for the clinical management of biliodigestive anastomoses.