Silver Nanofunctionalized Stent after Radiofrequency Ablation Suppresses Tissue Hyperplasia and Bacterial Growth

Abstract

Intraductal radiofrequency (RF) ablation combined with placement of a self-expandable metal stent (SEMS) for malignant biliary obstruction has risks such as stent- and heat-induced biliary sludge and restenosis. Here, we investigated the efficacy of a silver nanoparticles (AgNPs)-coated SEMS to inhibit tissue hyperplasia and bacterial growth caused by RF ablation with stent placement in the rabbit bile duct. The release behavior and antibacterial effects of AgNPs-coated SEMSs were evaluated. Then, SEMSs were successfully placed in all rabbits immediately after RF ablation. Ag ions were rapidly released at the beginning and then showed a gradual release behavior. The AgNPs-coated SEMS significantly inhibited bacterial activity compared to the uncoated SEMS (p < 0.05). Cholangiography and histological examination confirmed that the level of tissue hyperplasia was significantly lower in the AgNPs group than in the control group (all p < 0.05). Immunohistochemistry analyses revealed that TUNEL-, HSP 70-, and α-SMA-positive areas were significantly lower in the AgNPs group than in the control group (all p < 0.05). Intraductal RF ablation combined with nanofunctionalized stent placement represents a promising new approach for suppressing thermal damage as well as stent-induced tissue hyperplasia and bacterial growth.

3D-printed versatile biliary stents with nanoengineered surface for anti-hyperplasia and antibiofilm formation

“…Bacteria with a high multiplication rate adhering to the stent form concrete biofilms. Thus, recent studies on biliary stents have adopted antibacterial strategies to suppress the biofilm formation [ 3 , 55 , [104] , [105] , [106] , [107] , [108] , [109] , [110] ]. Among various candidates, Zn-ion-releasing materials have been widely explored as antibacterial agents owing to their nonspecific antimicrobial characteristics and long-lasting release of ions [ 46 , [111] , [112] , [113] ].…”

“…However, there were no significant differences between the PCL and fPCL stent groups and SRL@PCL and Zn-SRL@PCL stent groups ( Table S3 ). Hematology assays of the ALT, ALP, GGT, and TB levels are commonly used as indicators of the chemistry of liver function and disorders, including bile duct obstruction, cholestasis, and jaundice [ 55 , 124 ]. ALT, which is mainly present in the cell cytoplasm, is highly sensitive to liver cell injury and is a reliable marker for detecting both acute and subacute hepatocellular injuries [ 125 , 126 ].…”

“…Under general anesthesia, laparotomy was performed to expose the bile duct, as previously described [ 55 , 56 ]. Subsequently, a 2-cm longitudinal epigastrium incision was made to identify the ampulla of the Vater of the duodenum.…”

“…Pre-procedural cholangiography was performed via the angiocatheter using a contrast medium to check the anatomical variables of the CBD. The diameter of the stent was selected considering the mean diameter (2.31 ± 0.51 mm) of the normal CBD in rabbits weighting 2.8–3.4 kg [ 55 , 56 ]. The 3-mm-diameter and 10-mm-long balloon catheter, which was a crimped PCL stent, was inserted over the guide wire into the CBD.…”

“…Surgical exploration of the duodenum, liver, and biliary duct was conducted. The degrees of granulation tissue formation and biliary sludge were evaluated by gross examination [ 55 , 56 ]. Tissue samples were fixed in 10% neutral buffered formalin for 48 h, and the middle portion of the stented CBD was transversely sectioned for histological analysis.…”