Skip to main content
SpringerLink
Log in

Preclinical Evaluation of an Everolimus-Eluting Bioresorbable Vascular Scaffold Via a Long-Term Rabbit Iliac Artery Model

  • Original Article
  • Published:
Tissue Engineering and Regenerative Medicine Aims and scope

Abstract

Background:

Biodegradable poly (l-lactic acid) (PLLA), a bio safe polymer with a large elastic modulus, is widely used in biodegradable medical devices. However, because of its poor mechanical properties, a PLLA strut must be made twice as thick as a metal strut for adequate blood vessel support. Therefore, the mechanical properties of a drug-eluting metal-based stents (MBS) and a bioresorbable vascular scaffolds (BVS) were evaluated and their safety and efficacy were examined via a long-term rabbit iliac artery model.

Methods:

The surface morphologies of the MBSs and BVSs were investigated via optical and scanning electron microscopy. An everolimus-eluting (EE) BVS or an EE-MBS was implanted into rabbit iliac arteries at a 1.1:1 stent-to-artery ratio. Twelve months afterward, stented iliac arteries from each group were analyzed via X-ray angiography, optical coherence tomography (OCT), and histopathologic evaluation.

Results:

Surface morphology analysis of the EE coating on the MBS confirmed that it was uniform and very thin (4.7 μm). Comparison of the mechanical properties of the EE-MBS and EE-BVS showed that the latter outperformed the former in all aspects (radial force (2.75 vs. 0.162 N/mm), foreshortening (0.24% vs. 1.9%), flexibility (0.52 vs. 0.19 N), and recoil (3.2% vs. 6.3%). At all time points, the percent area restenosis was increased in the EE-BVS group compared to the EE-MBS group. The OCT and histopathological analyses indicate no significant changes in strut thickness.

Conclusion:

BVSs with thinner struts and shorter resorption times should be developed. A comparable long-term safety/efficacy evaluation after complete absorption of BVSs should be conducted.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9
Fig. 10

Similar content being viewed by others

References

  1. Sahin B, Ilgun G. Risk factors of deaths related to cardiovascular diseases in World Health Organization (WHO) member countries. Health Soc Care Community. 2022;30:73–80.

    Article  PubMed  Google Scholar 

  2. Thygesen K, Alpert JS, White HD, Jaffe AS, Apple FS, Galvani M, et al. Universal definition of myocardial infarction. Circulation. 2007;116:2634–53.

    Article  PubMed  Google Scholar 

  3. Reimer KA, Jennings RB, Tatum AH. Pathobiology of acute myocardial ischemia: metabolic, functional and ultrastructural studies. Am J Cardiol. 1983;52:72A-81.

    Article  CAS  PubMed  Google Scholar 

  4. Ahmed K, Jeong MH, Chakraborty R, Hong YJ, Sim DS, Hwang SH, et al. Percutaneous coronary intervention with drug-eluting stent implantation vs. coronary artery bypass grafting for multivessel coronary artery disease in metabolic syndrome patients with acute myocardial infarction. Circ J. 2012;76:721–8.

    Article  CAS  PubMed  Google Scholar 

  5. Jeong MH. Current status of the development of new-drug eluting stents. Korean J Med. 2009;76:544–8.

    Google Scholar 

  6. Gruntzig A. Transluminal dilatation of coronary-artery stenosis. Lancet. 1978;1:263.

    Article  CAS  PubMed  Google Scholar 

  7. Sim DS, Jeong MH. Development of novel drug-eluting stents for acute myocardial infarction. Chonnam Med J. 2017;53:187–95.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Joner M, Finn AV, Farb A, Mont EK, Kolodgie FD, Ladich E, et al. Pathology of drug-eluting stents in humans: delayed healing and late thrombotic risk. J Am Coll Cardiol. 2006;48:193–202.

    Article  PubMed  Google Scholar 

  9. Zamiri P, Kuang Y, Sharma U, Ng TF, Busold RH, Rago AP, et al. The biocompatibility of rapidly degrading polymeric stents in porcine carotid arteries. Biomaterials. 2010;31:7847–55.

    Article  CAS  PubMed  Google Scholar 

  10. Peng HY, Chen M, Zheng B, Wang XG, Huo Y. Long-term effects of novel biodegradable, polymer-coated, sirolimus-eluting stents on neointimal formation in a porcine coronary model. Int Heart J. 2009;50:811–22.

    Article  CAS  PubMed  Google Scholar 

  11. Kim MC, Jeong MH, Sim DS, Hong YJ, Kim JH, Ahn Y. Intravascular ultrasound-guided treatment for in-stent restenosis associated with stent fracture in overlapped drug-eluting stents. Chonnam Med J. 2019;55:165–7.

    Article  PubMed  PubMed Central  Google Scholar 

  12. Jinnouchi H, Torii S, Sakamoto A, Kolodgie FD, Virmani R, Finn AV. Fully bioresorbable vascular scaffolds: lessons learned and future directions. Nat Rev Cardiol. 2019;16:286–304.

    Article  CAS  PubMed  Google Scholar 

  13. Zhang ZQ, Yang YX, Li JA, Zeng RC, Guan SK. Advances in coatings on magnesium alloys for cardiovascular stents - a review. Bioact Mater. 2021;6:4729–57.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Park SA, Lee SJ, Lim KS, Bae IH, Lee JH, Kim WD, et al. In vivo evaluation and characterization of a bio-absorbable drug-coated stent fabricated using a 3D-printing system. Mater Lett. 2015;141:355–8.

    Article  CAS  Google Scholar 

  15. Chevalier B, Abizaid A, Carrie D, Frey N, Lutz M, Weber-Albers J, et al. Clinical and angiographic outcomes with a novel radiopaque sirolimus-eluting bioresorbable vascular scaffold. Circ Cardiovasc Interv. 2019;12:e007283.

    Article  CAS  PubMed  Google Scholar 

  16. Jezewski MP, Kubisa MJ, Eyileten C, De Rosa S, Christ G, Lesiak M, et al. Bioresorbable vascular scaffolds-dead end or still a rough diamond. J Clin Med. 2019;8:2167.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Bae IH, Lim KS, Park JK, Park DS, Lee SY, Jang EJ, et al. Mechanical behavior and in vivo properties of newly designed bare metal stent for enhanced flexibility. J Ind Eng Chem. 2015;21:1295–300.

    Article  CAS  Google Scholar 

  18. Oh S, Jeong MH, Park DS, Kim M, Kim JH, Hyun DY, et al. Successful implantation of a novel polymer-free everolimus-eluting stent using nitrogen-doped titanium dioxide film with good patency on follow-up angiography: a case report. Medicine (Baltimore). 2022;101:e29666.

    Article  CAS  PubMed  Google Scholar 

  19. Schwartz RS, Huber KC, Murphy JG, Edwards WD, Camrud AR, Vlietstra RE, et al. Restenosis and the proportional neointimal response to coronary artery injury: results in a porcine model. J Am Coll Cardiol. 1992;19:267–74.

    Article  CAS  PubMed  Google Scholar 

  20. Schwartz RS, Edelman E, Virmani R, Carter A, Granada JF, Kaluza GL, et al. Drug-eluting stents in preclinical studies: updated consensus recommendations for preclinical evaluation. Circ Cardiovasc Interv. 2008;1:143–53.

    Article  PubMed  PubMed Central  Google Scholar 

  21. Iqbal J, Gunn J, Serruys PW. Coronary stents: historical development, current status and future directions. Br Med Bull. 2013;106:193–211.

    Article  CAS  PubMed  Google Scholar 

  22. Kee WJ, Jeong MH, Jang SY, Lee MG, Park KH, Sim DS, et al. Very late stent thrombosis due to neointimal rupture after paclitaxel-eluting stent implantation. Korean Circ J. 2011;41:754–8.

    Article  PubMed  PubMed Central  Google Scholar 

  23. Kim Y, Bae S, Jeong MH, Ahn Y, Kim CJ, Cho MC, et al. One-year efficacy and safety of everolimus-eluting bioresorbable scaffolds in the setting of acute myocardial infarction. PLoS One. 2020;15:e0235673.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Kim HI, Ishihara K, Lee S, Seo JH, Kim HY, Suh D, et al. Tissue response to poly(L-lactic acid)-based blend with phospholipid polymer for biodegradable cardiovascular stents. Biomaterials. 2011;32:2241–7.

    Article  CAS  PubMed  Google Scholar 

  25. McDonald RA, Halliday CA, Miller AM, Diver LA, Dakin RS, Montgomery J, et al. reducing in-stent restenosis: therapeutic manipulation of miRNA in vascular remodeling and inflammation. J Am Coll Cardiol. 2015;65:2314–27.

    Article  PubMed  PubMed Central  Google Scholar 

  26. Nebeker JR, Virmani R, Bennett CL, Hoffman JM, Samore MH, Alvarez J, et al. Hypersensitivity cases associated with drug-eluting coronary stents: a review of available cases from the research on adverse drug events and reports (RADAR) project. J Am Coll Cardiol. 2006;47:175–81.

    Article  PubMed  Google Scholar 

  27. Sanchez-Fructuoso AI. Everolimus: an update on the mechanism of action, pharmacokinetics and recent clinical trials. Expert Opin Drug Metab Toxicol. 2008;4:807–19.

    Article  CAS  PubMed  Google Scholar 

  28. Park DS, Bae IH, Jeong MH, Lim KS, Sim DS, Hong YJ, et al. In vitro and in vivo evaluation of a novel polymer-free everolimus-eluting stent by nitrogen-doped titanium dioxide film deposition. Mater Sci Eng C Mater Biol Appl. 2018;91:615–23.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This work was supported by a Korean Medical Device Development Fund Grant funded by the Korean government (the Ministries of Science and ICT; Trade, Industry, and Energy; Health and Welfare; and Food and Drug Safety) (1711138916, KMDF_PR_20200901_0280 and 1711137864,KMDF_PR_20200901_0005). This research was also supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Korean Ministry of Education (NRF-2020R1I1A3A04036675).

Author information

Authors and Affiliations

  1. The Korean Cardiovascular Stent Research Institute, Jangsung, 57248, Republic of Korea

    Dae Sung Park, Myung Ho Jeong, Yu Jeong Jin, Mi Hyang Na, Doo Sun Sim, Munki Kim, Kyung Hoon Cho, Dae Young Hyun, Seok Oh, Jeong Ha Kim, Young Joon Hong, Ju Han Kim & Youngkeun Ahn

  2. The Cardiovascular Convergence Research Center of Chonnam National University Hospital Designated by the Korean Ministry of Health and Welfare, Gwangju, 61469, Republic of Korea

    Dae Sung Park, Myung Ho Jeong, Doo Sun Sim, Munki Kim, Kyung Hoon Cho, Dae Young Hyun, Seok Oh, Jeong Ha Kim, Young Joon Hong, Ju Han Kim & Youngkeun Ahn

  3. The Research Institute of Medical Sciences, Chonnam National University, Gwangju, 61469, Republic of Korea

    Dae Sung Park

  4. Department of Cardiology, Chonnam National University Hospital, Gwangju, 61469, Republic of Korea

    Myung Ho Jeong, Doo Sun Sim, Kyung Hoon Cho, Dae Young Hyun, Seok Oh, Young Joon Hong, Ju Han Kim, Youngkeun Ahn & Jeong Hun Kim

  5. The Futuristic Animal Research Center, The Korean Research Institute of Bioscience and Biotechnology, Ochang, 28116, Republic of Korea

    Kyung Seob Lim

  6. CGBio Co. Ltd., Seoul, Republic of Korea

    Jun-Kyu Park & Han Ki Kim

Authors
  1. Dae Sung Park
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Myung Ho Jeong
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yu Jeong Jin
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Mi Hyang Na
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Doo Sun Sim
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Munki Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Kyung Hoon Cho
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Dae Young Hyun
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Seok Oh
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Jeong Ha Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Kyung Seob Lim
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Jun-Kyu Park
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Han Ki Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Young Joon Hong
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Ju Han Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. Youngkeun Ahn
    View author publications

    You can also search for this author in PubMed Google Scholar

  17. Jeong Hun Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Myung Ho Jeong.

Ethics declarations

Conflict of interest

The authors declare that they have no competing financial interests.

Ethical statement

The animal studies were performed after receiving approval from the Institutional Animal Care and Use Committee (IACUC) in Chonnam National University Hospital (IACUC approval No. CNUHIACUC-21004).

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Park, D.S., Jeong, M.H., Jin, Y.J. et al. Preclinical Evaluation of an Everolimus-Eluting Bioresorbable Vascular Scaffold Via a Long-Term Rabbit Iliac Artery Model. Tissue Eng Regen Med 20, 239–249 (2023). https://doi.org/10.1007/s13770-023-00518-z

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13770-023-00518-z

Keywords

Search

Navigation