In vitro and in vivo assessment of a bilayered degradable rapamycin-eluting stent for ureteral stricture caused by holmium: YAG laser lithotripsy

Ureteral stricture caused by holmium: YAG laser lithotripsy is one of the most challenging issues for urologists. Currently, evidence for rapamycin application in reducing ureterostenosis is not sufficient. This study aimed to assess the inhibition of ureteral stricture of rapamycin-eluting stents in vitro and in vivo. A bilayered drug-eluting ureteral stent consisted of drug blending with poly (lactic-co-glycolic acid) (PU/drug stent), which was over-layered by polycaprolactone (PCL) by ultrasonic atomizing spraying. Stent morphology was observed by scanning electron microscope. A kidney-ureter-bladder model was established to simulate the stents-releasing condition, and high-performance liquid chromatography was used to measure the drug release rate. The inhibitory proliferation was detected by CCK-8. The bladder of rats was injured through electro tome, and stents were implanted for 7, 14, and 28 days. The effects of drug-eluting stents was investigated by hematoxylin-eosin staining, immunofluorescence staining, realtime quantitative polymerase chain reaction and western blot. The bilayered stents could block the burst loss of the drug and maintained a sustained delivery period because of the 5.3 mu m thickness of the PCL layer. The relative growth rates of cells plotted inhibitory effect on the proliferation of human urethral scar fibroblast cells. For in vivo results of 28 days, the bilayered stent maintained structural integrity and induced less deposition of crystals, thinner and less lamina propria connective tissues were formed, and alpha-SMA and TGF-beta 1 were downregulated. Bilayered rapamycin-eluting stent is significantly effective in alleviating fibrosis in in vitro and in vivo models.