Recent therapeutic strategies to suppress restenosis after biliary stent placement are insufficient. Here, we demonstrate the usefulness of a self-expandable metal stent (SEMS), a stent mesh coated with silver nanoparticles (AgNPs), for suppression of both stent-induced tissue hyperplasia and biliary sludge formation in the rabbit bile duct. The AgNP-coated SEMSs were prepared using a simple bio-inspired surface modification process. Then, the prepared SEMSs were successfully placed in 22 of 24 rabbits. Sludge formation in the AgNP-coated SEMS groups was significantly decreased compared to the control group on gross findings. Cholangiographic and histologic examinations demonstrated significantly decreased tissue hyperplasia in the AgNP-coated SEMS groups compared with the control group (p < 0.05 for all). There were no differences between the AgNP-coated SEMS groups (p > 0.05 for all). However, in the group coated with the greatest concentration of AgNPs (Group D), submucosal fibrosis was thicker than in the other AgNP-coated groups (p < 0.05 for all). The AgNP-coated metallic stent mesh significantly suppressed stent-induced tissue hyperplasia and biliary sludge formation in the rabbit bile duct. Taken together, the AgNP coating strategy developed in this study could be widely utilized in non-vascular medical devices for anti-bacterial and anti-inflammatory responses.
Various preclinical studies with developed Eustachian tube (ET) stents are in progress but have not yet been clinically applied. ET stent is limited by stent-induced tissue hyperplasia in preclinical studies. The effectiveness of sirolimus-eluting cobalt–chrome alloy stent (SES) in suppressing stent-induced tissue hyperplasia after stent placement in the porcine ET model was investigated. Six pigs were divided into two groups (i.e., the control and the SES groups) with three pigs for each group. The control group received an uncoated cobalt–chrome alloy stent (n = 6), and the SES group received a sirolimus-eluting cobalt–chrome alloy stent (n = 6). All groups were sacrificed 4 weeks after stent placement. Stent placement was successful in all ETs without procedure-related complications. None of the stents was able to keep its round shape as original, and mucus accumulation was observed inside and around the stent in both groups. On histologic analysis, the tissue hyperplasia area and the thickness of submucosal fibrosis were significantly lower in the SES group than in the control group. SES seems to be effective in suppressing stent-induced tissue hyperplasia in porcine ET. However, further investigation was required to verify the optimal stent materials and antiproliferative drugs.
There is a clinical need to develop a stent to treat obstructive and refractory Eustachian tube dysfunction (ETD) after balloon Eustachian tuboplasty. An animal model for stent placement in the Eustachian tube (ET) is needed to develop optimal designs and materials, as stents for ETD have not been clinically applied. The purpose of this study was to evaluate the technical feasibility of stent placement and histological changes in a porcine ET model. Six ETs were evaluated in three pigs. Cobalt–chrome alloy stents with two different diameters were placed in the left and right ET of each animal (right, 3.5 mm; left, 2.5 mm). The outcomes were assessed by endoscopic and fluoroscopic imaging during the procedure, computed tomography after the procedure, and by histological examinations. Stent placement was technically successful in all specimens after metallic guiding sheaths were located in the nasopharyngeal end of the ET. The mean luminal diameters of the proximal, middle, and distal portions of the larger stents in the right ETs were 3.48 mm, 2.54 mm, and 2.15 mm, respectively. In the left ETs using smaller stents, these values were 2.49 mm, 1.73 mm, and 1.42 mm, respectively. The diameters of the inserted stents differed by stent location and the original diameter. Histological findings showed tissue hyperplasia with severe inflammatory cell infiltration at 4 weeks after stent placement. In conclusion, stent placement into the porcine ET was technically feasible, and stent-induced tissue hyperplasia was significantly evident. The luminal configuration of the placed ET stent changed according to its non-elastic nature and anatomical features of the porcine ET. Using this model, ET stents of various materials and designs with anti-inflammatory or anti-proliferative drugs can be optimized for future treatments of ET dysfunction.
Background: Irreversible electroporation (IRE) has been investigated in the alimentary tract; however, the lack of dedicated electrodes and insufficient tissue responses made its application limited. The aim of this study was to investigate the efficacy and safety of image-guided stent-directed IRE in the rat esophagus.Methods: The bipolar self-expandable electrode (SE) was developed using the braiding technique. A finite element analysis was performed to validate optimal electrical field strength for the rat esophagus. A total of 40 out of 50 rats received stent-directed IRE and were sacrificed at 10 h, 3 days, 7 days, and 28 days of 10 each. The remaining ten rats underwent a sham procedure. The outcomes of stent-directed IRE were assessed by esophagography and histological responses.Results: Stent-directed IRE was technically successful in all rats with mild muscle contraction. The heart rate dropped immediately and gradually recovered at 180 s. TUNEL and caspase-3 with submucosal thickness significantly increased at 10 h and Day 3 compared with those of the sham control (all p < 0.001). The thickness of epithelial layers with collagen deposition significantly decreased at 10 h and Day 3 (all p < 0.001), however, increased at Day 7 compared with that of the sham control (all p < 0.05). The Ki67-positive deposition significantly increased at Day 3 and 7 compared with that of the sham control (all p < 0.001). All variables were similar to those of the sham control at Day 28.Conclusion: Image-guided stent-directed IRE was effective and safe in the rat esophagus. It seems to have effectively and evenly induced cell death and gradually recovered with cellular regeneration.
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