Skip to main content
SpringerLink
Log in

Design and Validation of a Novel Ferromagnetic Bare Metal Stent Capable of Capturing and Retaining Endothelial Cells

  • Published:
Annals of Biomedical Engineering Aims and scope Submit manuscript

Abstract

Rapid healing of vascular stents is important for avoiding complications associated with stent thrombosis, restenosis, and bleeding related to antiplatelet drugs. Magnetic forces can be used to capture iron-labeled endothelial cells immediately following stent implantation, thereby promoting healing. This strategy requires the development of a magnetic stent that is biocompatible and functional. We designed a stent from the weakly ferromagnetic 2205 stainless steel using finite element analysis. The final design exhibited a principal strain below the fracture limit of 30% during crimping and expansion. Ten stents were fabricated and validated experimentally for fracture resistance. Another 10 stents magnetized with a neodymium magnet showed a magnetic field in the range of 100–750 mG. The retained magnetism was sufficiently strong to capture magnetically-labeled endothelial cells on the stent surfaces during in vitro studies. Magnetically-labeled endothelial cell capture was also verified in vivo after 7 days following coronary implantation in 4 pigs using histological analysis. Images of the stented blood vessels showed uniform endothelium formation on the stent surfaces. In conclusion, we have designed a ferromagnetic bare metal stent from 2205 stainless steel that is functional, biocompatible, and able to capture and retain magnetically-labeled endothelial cells in order to promote rapid stent healing.

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

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7

Similar content being viewed by others

References

  1. Achneck, H. E., R. M. Jamiolkowski, A. E. Jantzen, J. M. Haseltine, W. O. Lane, J. K. Huang, L. J. Galinat, M. J. Serpe, F. H. Lin, M. Li, A. Parikh, L. Ma, T. Chen, B. Sileshi, C. A. Milano, C. S. Wallace, T. V. Stabler, J. D. Allen, G. A. Truskey, and J. H. Lawson. The biocompatibility of titanium cardiovascular devices seeded with autologous blood-derived endothelial progenitor cells: EPC-seeded antithrombotic ti implants. Biomaterials 32:10–18, 2011.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  2. Austin, D., K. G. Oldroyd, A. McConnachie, R. Slack, H. Eteiba, A. D. Flapan, K. P. Jennings, R. J. Northcote, A. C. Pell, I. R. Starkey, and J. P. Pell. Drug-eluting stents versus bare-metal stents for off-label indications: a propensity score-matched outcome study. Circ. Cardiovasc. Interv. 1:45–52, 2008.

    Article  PubMed  Google Scholar 

  3. Aviles, M. O., H. T. Chen, A. D. Ebner, A. J. Rosengart, M. D. Kaminski, and J. A. Ritter. In vitro study of ferromagnetic stents for implant assisted-magnetic drug targeting. J. Magn. Magn. Mater. 311:306–311, 2007.

    Article  CAS  Google Scholar 

  4. Barlow, J. Optimal stress locations in finite-element models. Int. J. Numer. Methods Eng. 10:243–251, 1976.

    Article  Google Scholar 

  5. Barlow, J. More on optimal stress points—reduced integration, element distortions and error estimation. Int. J. Numer. Methods Eng. 28:1487–1504, 1989.

    Article  Google Scholar 

  6. Chorny, M., I. Fishbein, B. B. Yellen, I. S. Alferiev, M. Bakay, S. Ganta, R. Adamo, M. Amiji, G. Friedman, and R. J. Levy. Targeting stents with local delivery of paclitaxel-loaded magnetic nanoparticles using uniform fields. Proc. Natl. Acad. Sci. USA 107:8346–8351, 2010.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  7. Duckers, H. J., S. Silber, R. de Winter, P. den Heijer, B. Rensing, M. Rau, H. Mudra, E. Benit, S. Verheye, W. Wijns, and P. W. Serruys. Circulating endothelial progenitor cells predict angiographic and intravascular ultrasound outcome following percutaneous coronary interventions in the healing-ii trial: evaluation of an endothelial progenitor cell capturing stent. EuroIntervention 3:67–75, 2007.

    Article  PubMed  Google Scholar 

  8. Duckers, H. J., T. Soullie, P. den Heijer, B. Rensing, R. J. de Winter, M. Rau, H. Mudra, S. Silber, E. Benit, S. Verheye, W. Wijns, and P. W. Serruys. Accelerated vascular repair following percutaneous coronary intervention by capture of endothelial progenitor cells promotes regression of neointimal growth at long term follow-up: final results of the healing ii trial using an endothelial progenitor cell capturing stent (genous r stent). EuroIntervention 3:350–358, 2007.

    Article  PubMed  Google Scholar 

  9. Edelman, E. R., P. Seifert, A. Groothuis, A. Morss, D. Bornstein, and C. Rogers. Gold-coated NIR stents in porcine coronary arteries. Circulation 103:429–434, 2001.

    Article  CAS  PubMed  Google Scholar 

  10. Garg, S., and P. W. Serruys. Coronary stents: looking forward. J. Am. Coll. Cardiol. 56:S43–S78, 2010.

    Article  CAS  PubMed  Google Scholar 

  11. Gulati, R., D. Jevremovic, T. E. Peterson, S. Chatterjee, V. Shah, R. G. Vile, and R. D. Simari. Diverse origin and function of cells with endothelial phenotype obtained from adult human blood. Circ. Res. 93:1023–1025, 2003.

    Article  CAS  PubMed  Google Scholar 

  12. Gunn, J., and D. Cumberland. Stent coatings and local drug delivery—state of the art. Eur. Heart J. 20:1693–1700, 1999.

    Article  CAS  PubMed  Google Scholar 

  13. Gunn, J., and D. Cumberland. Does stent design influence restenosis? Eur. Heart J. 20:1009–1013, 1999.

    Article  CAS  PubMed  Google Scholar 

  14. Jantzen, A. E., W. O. Lane, S. M. Gage, J. M. Haseltine, L. J. Galinat, R. M. Jamiolkowski, F. H. Lin, G. A. Truskey, and H. E. Achneck. Autologous endothelial progenitor cell-seeding technology and biocompatibility testing for cardiovascular devices in large animal model. J. Vis. Exp. 55:3197, 2011.

    PubMed  Google Scholar 

  15. Jantzen, A. E., W. O. Lane, S. M. Gage, R. M. Jamiolkowski, J. M. Haseltine, L. J. Galinat, F. H. Lin, J. H. Lawson, G. A. Truskey, and H. E. Achneck. Use of autologous blood-derived endothelial progenitor cells at point-of-care to protect against implant thrombosis in a large animal model. Biomaterials 32:8356–8363, 2011.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  16. Kastrati, A., J. Mehilli, J. Dirschinger, F. Dotzer, H. Schuhlen, F. J. Neumann, M. Fleckenstein, C. Pfafferott, M. Seyfarth, and A. Schomig. Intracoronary stenting and angiographic results: strut thickness effect on restenosis outcome (isar-stereo) trial. Circulation 103:2816–2821, 2001.

    Article  CAS  PubMed  Google Scholar 

  17. Kempe, H., and M. Kempe. The use of magnetite nanoparticles for implant-assisted magnetic drug targeting in thrombolytic therapy. Biomaterials 31:9499–9510, 2010.

    Article  CAS  PubMed  Google Scholar 

  18. Kipshidze, N., G. Dangas, M. Tsapenko, J. Moses, M. B. Leon, M. Kutryk, and P. Serruys. Role of the endothelium in modulating neointimal formation—vasculoprotective approaches to attenuate restenosis after percutaneous coronary interventions. J. Am. Coll. Cardiol. 44:733–739, 2004.

    CAS  PubMed  Google Scholar 

  19. Lally, C., F. Dolan, and P. J. Prendergast. Cardiovascular stent design and vessel stresses: a finite element analysis (vol 38, pg 1574, 2005). J. Biomech. 39:1760, 2006.

    Article  Google Scholar 

  20. Lee, S. J., J. R. Jeong, S. C. Shin, J. C. Kim, Y. H. Chang, Y. M. Chang, and J. D. Kim. Nanoparticles of magnetic ferric oxides encapsulated with poly(d, l latide-co-glycolide) and their applications to magnetic resonance imaging contrast agent. J. Magn. Magn. Mater. 272:2432–2433, 2004.

    Article  Google Scholar 

  21. Liu, Z. Y., C. F. Dong, X. G. Li, Q. Zhi, and Y. F. Cheng. Stress corrosion cracking of 2205 duplex stainless steel in H2S-CO2 environment. J. Mater. Sci. 44:4228–4234, 2009.

    Article  CAS  Google Scholar 

  22. Liu, J. Y., L. Y. Zhao, Y. Y. Wang, D. Y. Li, D. Tao, L. Y. Li, and J. T. Tang. Magnetic stent hyperthermia for esophageal cancer: an in vitro investigation in the eca-109 cell line. Oncol. Rep. 27:791–797, 2012.

    PubMed  Google Scholar 

  23. Lu, A., G. Jia, G. Gao, and X. Wang. The effect of magnetic stent on coronary restenosis after percutaneous transluminal coronary angioplasty in dogs. Chin. Med. J. (Engl). 114:821–823, 2001.

    CAS  PubMed  Google Scholar 

  24. Mardinoglu, A., P. J. Cregg, K. Murphy, M. Curtin, and A. Prina-Mello. Theoretical modelling of physiologically stretched vessel in magnetisable stent assisted magnetic drug targeting application. J. Magn. Magn. Mater. 323:324–329, 2011.

    Article  CAS  Google Scholar 

  25. Marrey, R. V., R. Burgermeister, R. B. Grishaber, and R. O. Ritchie. Fatigue and life prediction for cobalt-chromium stents: a fracture mechanics analysis. Biomaterials 27:1988–2000, 2006.

    Article  CAS  PubMed  Google Scholar 

  26. Migliavacca, F., L. Petrini, V. Montanari, I. Quagliana, F. Auricchio, and G. Dubini. A predictive study of the mechanical behaviour of coronary stents by computer modelling. Med. Eng. Phys. 27:13–18, 2005.

    Article  PubMed  Google Scholar 

  27. Murphy, B. P., P. Savage, P. E. McHugh, and D. F. Quinn. The stress-strain behavior of coronary stent struts is size dependent. Ann. Biomed. Eng. 31:686–691, 2003.

    Article  CAS  PubMed  Google Scholar 

  28. Nebeker, J. R., R. Virmani, C. L. Bennett, J. M. Hoffman, M. H. Samore, J. Alvarez, C. J. Davidson, J. M. McKoy, D. W. Raisch, B. K. Whisenant, P. R. Yarnold, S. M. Belknap, D. P. West, J. E. Gage, R. E. Morse, G. Gligoric, L. Davidson, and M. D. Feldman. 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. 47:175–181, 2006.

    Article  PubMed  Google Scholar 

  29. Pache, J., A. Kastrati, J. Mehilli, H. Schuhlen, F. Dotzer, J. Hausleiter, M. Fleckenstein, F. J. Neumann, U. Sattelberger, C. Schmitt, M. Muller, J. Dirschinger, and A. Schomig. Intracoronary stenting and angiographic results: strut thickness effect on restenosis outcome (isar-stereo-2) trial. J. Am. Coll. Cardiol. 41:1283–1288, 2003.

    Article  PubMed  Google Scholar 

  30. Pislaru, S. V., A. Harbuzariu, G. Agarwal, T. Witt, R. Gulati, N. P. Sandhu, C. Mueske, M. Kalra, R. D. Simari, and G. S. Sandhu. Magnetic forces enable rapid endothelialization of synthetic vascular grafts. Circulation 114:I314–I318, 2006.

    Article  PubMed  Google Scholar 

  31. Pislaru, S. V., A. Harbuzariu, R. Gulati, T. Witt, N. P. Sandhu, R. D. Simari, and G. S. Sandhu. Magnetically targeted endothelial cell localization in stented vessels. J. Am. Coll. Cardiol. 48:1839–1845, 2006.

    Article  CAS  PubMed  Google Scholar 

  32. Pislaru, S. V., A. Harbuzariu, R. D. Simari, and G. Sandhu. Magnetization of stents and synthetic vascular grafts facilitates endothelial cell localization. Eur. Heart J. 27:510–510, 2006.

    Article  Google Scholar 

  33. Polyak, B., and G. Friedman. Magnetic targeting for site-specific drug delivery: applications and clinical potential. Expert Opin. Drug Deliv. 6:53–70, 2009.

    Article  CAS  PubMed  Google Scholar 

  34. Polyak, B., I. Fishbein, M. Chorny, I. Alferiev, D. Williams, B. Yellen, G. Friedman, and R. J. Levy. High field gradient targeting of magnetic nanoparticle-loaded endothelial cells to the surfaces of steel stents. Proc. Natl. Acad. Sci. USA 105:698–703, 2008.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  35. Rathel, T., H. Mannell, J. Pircher, B. Gleich, U. Pohl, and F. Krotz. Magnetic stents retain nanoparticle-bound antirestenotic drugs transported by lipid microbubbles. Pharm. Res. Dordr. 29:1295–1307, 2012.

    Article  CAS  Google Scholar 

  36. Sangiorgi, G., G. Melzi, P. Agostini, C. Cola, F. Clementi, P. Romitelli, R. Virmani, and A. Colombo. Engineering aspects of stents design and their translation into clinical practice. Ann. Ist. Super Santia 43:89–100, 2007.

    Google Scholar 

  37. Schneider, D. B., and D. A. Dichek. Intravascular stent endothelialization. A goal worth pursuing? Circulation 95:308–310, 1997.

    Article  CAS  PubMed  Google Scholar 

  38. Sethi, R., and C. H. Lee. Endothelial progenitor cell capture stent: safety and effectiveness. J. Interv. Cardiol. 25:493–500, 2012.

    Article  PubMed  Google Scholar 

  39. Song, X. T., H. G. Zhu, X. S. Yang, F. Yuan, and S. Z. Lu. Stents coated with sirolimus and anti-cd34 antibody can optimize the performance of sirolimus-eluting stents. Zhonghua Xin Xue Guan Bing Za Zhi. 39:997–1004, 2011.

    PubMed  Google Scholar 

  40. Tassiopoulos, A. K., and H. P. Greisler. Angiogenic mechanisms of endothelialization of cardiovascular implants: a review of recent investigative strategies. J. Biomater. Sci. Polym. E 11:1275–1284, 2000.

    Article  CAS  Google Scholar 

  41. Tefft, B. J., J. Y. Gooden, S. Uthamaraj, J. J. Harburn, M. Klabusay, D. R. Holmes, R. D. Simari, D. Dragomir-Daescu, and G. S. Sandhu. Magnetizable duplex steel stents enable endothelial cell capture. IEEE Trans. Magn. 49:463–466, 2013.

    Article  Google Scholar 

  42. Zhao, H., J. Van Humbeeck, J. Sohier, and I. De Scheerder. Electrochemical polishing of 316 l stainless steel slotted tube coronary stents. J. Mater. Sci. Mater. Med. 13:911–916, 2002.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

The authors thank Tyra Witt, Cheri Mueske, Brant Newman and Dr. Peter J. Psaltis, MBBS, Ph.D. for their valuable contributions to this study. The authors also thank Drs. Maria Kempe, Ph.D., Shu Q. Liu, Ph.D., Adriele Prina-Mello, Ph.D., and Tré R. Welch, Ph.D. for their suggestions in writing this manuscript. This study was financially supported by European Regional Development Fund—FNUSA-ICRC (No. CZ.1.05/1.100/02.0123), American Heart Association Scientist Development Grant (AHA #06-35185N) and The Grainger Innovation Fund—The Grainger Foundation.

Disclosures

The authors have no relevant disclosures.

Author information

Authors and Affiliations

  1. Division of Engineering, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA

    Susheil Uthamaraj & Dan Dragomir-Daescu

  2. Division of Cardiovascular Diseases, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA

    Brandon J. Tefft & Gurpreet S. Sandhu

  3. Integrated Center of Cellular Therapy and Regenerative Medicine, ICRC, St. Anne’s University Hospital, Pekarska 53, 65691, Brno, Czech Republic

    Martin Klabusay

  4. Department of Cardioangiology, ICRC, St. Anne’s University Hospital, Pekarska 53, 65691, Brno, Czech Republic

    Ota Hlinomaz

  5. Mayo Clinic College of Medicine, 200 First Street SW, Rochester, MN, 55905, USA

    Gurpreet S. Sandhu & Dan Dragomir-Daescu

Authors
  1. Susheil Uthamaraj
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Brandon J. Tefft
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Martin Klabusay
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ota Hlinomaz
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Gurpreet S. Sandhu
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Dan Dragomir-Daescu
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Dan Dragomir-Daescu.

Additional information

Associate Editor Andreas Anayiotos oversaw the review of this article.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Uthamaraj, S., Tefft, B.J., Klabusay, M. et al. Design and Validation of a Novel Ferromagnetic Bare Metal Stent Capable of Capturing and Retaining Endothelial Cells. Ann Biomed Eng 42, 2416–2424 (2014). https://doi.org/10.1007/s10439-014-1088-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10439-014-1088-3

Keywords

Search

Navigation