Balloon-Expandable Biodegradable Stents Versus Self-Expandable Metallic Stents: A Comparison Study of Stent-Induced Tissue Hyperplasia in the Rat Urethra

  • Jung-Hoon Park
  • Tae-Hyung Kim
  • Young Chul Cho
  • Nader Bakheet
  • Seung Ok Lee
  • Seong-Hun KimEmail author
  • Kun Yung KimEmail author
Laboratory Investigation



To compare the degrees of stent-induced tissue hyperplasia of balloon-expandable, biodegradable stents (BEBSs) with those of self-expandable metallic stents (SEMSs) in a rat urethral model.

Materials and Methods

A total of 20 rats were randomized into two groups. The BEBS group (n = 10) received a poly-l-lactic acid (PLLA) biodegradable stent. The SEMS group (n = 10) received a nitinol bare stent. All rats were killed eight weeks after stent placement. The degree of stent-induced tissue hyperplasia was assessed by comparing the results of retrograde urethrography and histologic examination between the two groups.


Stent placement was technically successful in all rats. Two rats in the BEBS group were excluded due to procedure-related death. The mean luminal diameter of stented urethra on urethrograms was not significantly different at 4 and 8 weeks between the two groups. On histologic analysis, the percentage of granulation tissue area (p < 0.001) and the thickness of papillary projection (p < 0.001) were significantly higher in the BEBS group compared with the SEMS group. The inflammatory cell infiltration showed a clear tendency to significance (p = 0.050). There were no statistical differences in the number of epithelial layers and the thickness of submucosal fibrosis between the two groups.


Formation of stent-induced tissue hyperplasia was significantly evident in the rat urethra with similar degrees between the BEBS and the SEMS. The BEBS was associated with a thicker papillary projection and larger granulation tissue area resulting from higher inflammation compared with the SEMS.


Self-expandable metallic stent Biodegradable stent Tissue hyperplasia Poly-l-lactic acid 



This study was supported by Fund of Biomedical Research Institute (CUH2018-0022), Chonbuk National University Hospital

Compliance with Ethical Standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical Approval

All applicable international, national, and/or institutional guidelines for the care and use of animals were followed.

Informed Consent

For this type of study, informed consent is not required.


  1. 1.
    Song HY, Cho KS, Sung KB, Han YM, Kim YG, Kim CS. Self-expandable metallic stents in high-risk patients with benign prostatic hyperplasia: long-term follow-up. Radiology. 1995;195:655–60.CrossRefGoogle Scholar
  2. 2.
    Song HY, Lee DH, Seo TS, et al. Retrievable covered nitinol stents: experiences in 108 patients with malignant esophageal strictures. J Vasc Interv Radiol. 2002;13:285–93.CrossRefGoogle Scholar
  3. 3.
    Park JH, Lee JH, Song HY, et al. Over-the-wire versus through-the-scope stents for the palliation of malignant gastric outlet obstruction: a retrospective comparison study. Eur Radiol. 2016;26:4249–58.CrossRefGoogle Scholar
  4. 4.
    Song HY, Park H, Suh TS, et al. Recurrent traumatic urethral strictures near the external sphincter: treatment with a covered, retrievable, expandable nitinol stent—initial results. Radiology. 2003;226:433–40.CrossRefGoogle Scholar
  5. 5.
    Park JH, Song HY, Kim JH, et al. Polytetrafluoroethylene-covered retrievable expandable nitinol stents for malignant esophageal obstructions: factors influencing the outcome of 270 patients. AJR Am J Roentgenol. 2012;199:1380–6.CrossRefGoogle Scholar
  6. 6.
    Kim JH, Shin JH, Song HY, Shim TS, Yoon CJ, Ko GY. Benign tracheobronchial strictures: long-term results and factors affecting airway patency after temporary stent placement. AJR Am J Roentgenol. 2007;188:1033–8.CrossRefGoogle Scholar
  7. 7.
    Kim JH, Song HY, Choi EK, Kim KR, Shin JH, Lim JO. Temporary metallic stent placement in the treatment of refractory benign esophageal strictures: results and factors associated with outcome in 55 patients. Eur Radiol. 2009;19:384–90.CrossRefGoogle Scholar
  8. 8.
    Park JH, Song HY, Park JY, et al. Temporary stent placement with concurrent chemoradiation therapy in patients with unresectable oesophageal carcinoma: Is there an optimal time for stent removal? Eur Radiol. 2013;23:1940–5.CrossRefGoogle Scholar
  9. 9.
    Shaikh M, Kichenadasse G, Choudhury NR, Butler R, Garg S. Non-vascular drug eluting stents as localized controlled drug delivery platform: preclinical and clinical experience. J Control Release. 2013;172:105–17.CrossRefGoogle Scholar
  10. 10.
    Han K, Park JH, Yang SG, et al. EW-7197 eluting nano-fiber covered self-expandable metallic stent to prevent granulation tissue formation in a canine urethral model. PLoS ONE. 2018;13:e0192430.CrossRefGoogle Scholar
  11. 11.
    Kim EY, Song HY, Kim JH, et al. IN-1233 eluting covered metallic stent to prevent hyperplasia: experimental study in a rabbit esophageal model. Radiology. 2013;267:396–404.CrossRefGoogle Scholar
  12. 12.
    Lee SS, Shin JH, Han JM, et al. Histologic influence of paclitaxel-eluting covered metallic stents in a canine biliary model. Gastrointest Endosc. 2009;69:1140–7.CrossRefGoogle Scholar
  13. 13.
    Sigounas DE, Siddhi S, Plevris JN. Biodegradable esophageal stents in benign and malignant strictures: a single center experience. Endosc Int Open. 2016;4:618–23.CrossRefGoogle Scholar
  14. 14.
    Griffiths EA, Gregory CJ, Pursnani KG, Ward JB, Stockwell RC. The use of biodegradable (SX-ELLA) oesophageal stents to treat dysphagia due to benign and malignant oesophageal disease. Surg Endosc. 2012;26:2367–75.CrossRefGoogle Scholar
  15. 15.
    Isotalo T, Talja M, Valimaa T, Tormala P, Tammela TL. A bioabsorbable selfexpandable, self-reinforced poly-l-lactic acid urethral stent for recurrent urethral strictures: long-term results. J Endourol. 2002;16:759–62.CrossRefGoogle Scholar
  16. 16.
    Isotalo T, Tammela TL, Talja M, Valimaa T, Tormala P. A bioabsorbable self-expandable, self-reinforced poly-l-lactic acid urethral stent for recurrent urethral strictures: a preliminary report. J Urol. 1998;160:2033–6.CrossRefGoogle Scholar
  17. 17.
    Li YD, Song HY, Kim JH, et al. Evaluation of formation of granulation tissue caused by metallic stent placement in a rat urethral model. J Vasc Interv Radiol. 2010;21:1884–90.CrossRefGoogle Scholar
  18. 18.
    Kim KY, Park JH, Kim DH, et al. Sirolimus-eluting biodegradable poly-l-lactic acid stent to suppress granulation tissue formation in the rat urethra. Radiology. 2018;286:140–8.CrossRefGoogle Scholar
  19. 19.
    Park JH, Kim JH, Kim EY, et al. Bioreducible polymer-delivered siRNA targeting MMP-9: suppression of granulation tissue formation after bare metallic stent placement in a rat urethral model. Radiology. 2014;271:87–95.CrossRefGoogle Scholar
  20. 20.
    Nishio S, Kosuga K, Igaki K, et al. Long-term (> 10 years) clinical outcomes of first-in-human biodegradable poly-l-lactic acid coronary stents: Igaki-Tamai stents. Circulation. 2012;125:2343–53.CrossRefGoogle Scholar
  21. 21.
    Waksman R. Update on bioabsorbable stents: from bench to clinical. J Interv Cardiol. 2006;19:414–21.CrossRefGoogle Scholar
  22. 22.
    Cehn D, Su Z, Weng L, et al. Effect of inflammation on endothelial cells induced by poly-l-lactic acid degradation in vitro and in vivo. J Biomater Sci Polym Ed. 2018;29:1909–19.CrossRefGoogle Scholar
  23. 23.
    Bünger CM, Grabow N, Sternberg K, et al. A biodegradable stent based on poly(l-lactide) and poly(4-hydroxybutyrate) for peripheral vascular application: preliminary experience in the pig. J Endovasc Ther. 2007;14:725–33.CrossRefGoogle Scholar
  24. 24.
    Lee JH, Kim SJ, Park SI, et al. Development of a new hybrid biodegradable drug-eluting stent for the treatment of peripheral artery disease. Biomed Res Int. 2016;2016:6915789.Google Scholar
  25. 25.
    Li J, Chen J, Kirsner R. Pathophysiology of acute wound healing. Clin Dermatol. 2007;5:9–18.CrossRefGoogle Scholar
  26. 26.
    Diegelmann RF, Evans MC. Wound healing: an overview of acute, fibrotic and delayed healing. Front Biosci. 2004;9:283–9.CrossRefGoogle Scholar
  27. 27.
    Kim JH, Song HY, Park JH, et al. IN-1233, an ALK-5 inhibitor: prevention of granulation tissue formation after bare metallic stent placement in a rat urethral model. Radiology. 2010;255:75–82.CrossRefGoogle Scholar
  28. 28.
    Park JH, Park W, Cho S, et al. Nanofunctionalized stent-mediated local heat treatment for the suppression of stent-induced tissue hyperplasia. ACS Appl Mater Interfaces. 2018;10:29357–66.CrossRefGoogle Scholar
  29. 29.
    Teirstein PS, Massullo V, Jani S, et al. Catheter-based radiotherapy to inhibit restenosis after coronary stenting. N Engl J Med. 1997;336:1697–703.CrossRefGoogle Scholar
  30. 30.
    Shin JH, Song HY, Choi CG, et al. Tissue hyperplasia: influence of a paclitaxel eluting covered stent—preliminary study in a canine urethral model. Radiology. 2005;234:438–44.CrossRefGoogle Scholar
  31. 31.
    Kim EY, Shin JH, Jung YY, Shin DH, Song HY. A rat esophageal model to investigate stent-induced tissue hyperplasia. J Vasc Interv Radiol. 2010;21:1287–91.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature and the Cardiovascular and Interventional Radiological Society of Europe (CIRSE) 2019

Authors and Affiliations

  1. 1.Department of Radiology and Research Institute of RadiologyUniversity of Ulsan College of MedicineSeoulRepublic of Korea
  2. 2.Department of Biomedical Engineering Research CenterAsan Medical Center, University of Ulsan College of MedicineSeoulRepublic of Korea
  3. 3.Department of Radiological ScienceKangwon National UniversitySamcheok-SiRepublic of Korea
  4. 4.Division of Gastroenterology, Department of Internal Medicine, and Research Institute of Clinical MedicineChonbuk National UniversityJeonjuRepublic of Korea
  5. 5.Department of Radiology, and Research Institute of Clinical Medicine of Chonbuk National University-Biomedical Research InstituteChonbuk National UniversityJeonjuRepublic of Korea

Personalised recommendations