Comparison of three kinds of self-expandable metallic stents induced granulation tissue hyperplasia in the rabbit trachea.

To compare stent-induced granulation tissue hyperplasia of bare (SEMS), polyurethane-covered (PU-SEMS) and electrospun nanofibre-covered (EN-SEMS) self-expandable metallic stents in the rabbit trachea. Twenty-seven rabbits were randomly assigned to 3 groups that received SEMS, PU-SEMS or EN-SEMS. Computed tomography and sacrifice were performed as scheduled. Haematoxylin-eosin and Masson's trichrome staining protocols were performed for pathological analysis. The data for tracheal ventilation area ratio, qualitative histological scoring, number of epithelial layers, and thicknesses of papillary projection and submucosa were documented and statistically analysed. All stents were successfully placed under the guidance of fluoroscopy without complications. Post-stenting 3 and 7 days, computed tomography revealed that the fully expandable EN-SEMS was similar to the SEMS and PU-SEMS. The mean stented tissue score in the SEMS group was higher than those of both the PU-SEMS and EN-SEMS groups at 3 days post-stenting. The pathological findings suggested that there was no papillary projection formation 3 days after stent placement. The thickness of papillary projection in the SEMS group was significantly higher than those of the PU-SEMS and EN-SEMS groups at 7 days post-stenting. After stenting 4 weeks, the tracheal ventilation area ratio of SEMS, PU-SEMS and EN-SEMS was 0.214 ± 0.021, 0.453 ± 0.028 and 0.619 ± 0.033, respectively. There were significant between-group differences. In conclusion, the stent-induced granulation tissue formation in EN-SEMS is less severe than that of PU-SEMS and SEMS. EN-SEMS has smaller radial force, and the tracheal ventilation ratio after stent placement better than that of PU-SEMS.

Arsenic trioxide-eluting electrospun nanofiber-covered self-expandable metallic stent reduces granulation tissue hyperplasia in rabbit trachea.

Stent-related granulation tissue hyperplasia is a major complication that limits the application of stents in airways. In this study, an arsenic trioxide-eluting electrospun nanofiber-covered self-expandable metallic stent (ATO-NFCS) was developed. Poly-L-lactide-caprolactone (PLCL) was selected as the drug-carrying polymer. Stents with two different ATO contents (0.4% ATO/PLCL and 1.2% ATO/PLCL) were fabricated. The in vitro release in simulated airway fluid suggested that the total ATO release time was 1 d. The growth of human embryonic pulmonary fibroblasts (CCC-HPF-1), normal human bronchial epithelial cells and airway smooth muscle cells was inhibited by ATO. When embedded in paravertebral muscle, the nanofiber membrane showed good short-term and long-term biological effects. In an animal study, placement of the ATO-NFCS in the trachea through a delivery system under fluoroscopy was feasible. The changes in liver and kidney function 1 and 7 d after ATO-NFCS placement were within the normal range. On pathological examination, the heart, liver, spleen, lungs and kidneys were normal. The effectiveness of the ATO-NFCS in reducing granulation tissue hyperplasia and collagen deposition was demonstrated in the rabbit airway (n = 18) at 4 weeks. The present study preliminarily investigated the efficacy of the ATO-NFCS in reducing granulation tissue formation in the trachea of rabbits. The results suggest that the ATO-NFCS is safe in vivo, easy to place, and effective for the suppression of granulation tissue formation.