Advertisement

Annals of Biomedical Engineering

, Volume 42, Issue 12, pp 2416–2424 | Cite as

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

  • Susheil Uthamaraj
  • Brandon J. Tefft
  • Martin Klabusay
  • Ota Hlinomaz
  • Gurpreet S. Sandhu
  • Dan Dragomir-DaescuEmail author
Article

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.

Keywords

Magnetic stent Stent healing Endothelialization Finite element analysis Restenosis Thrombosis 

Notes

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.

References

  1. 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.PubMedCentralPubMedCrossRefGoogle Scholar
  2. 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.PubMedCrossRefGoogle Scholar
  3. 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.CrossRefGoogle Scholar
  4. 4.
    Barlow, J. Optimal stress locations in finite-element models. Int. J. Numer. Methods Eng. 10:243–251, 1976.CrossRefGoogle Scholar
  5. 5.
    Barlow, J. More on optimal stress points—reduced integration, element distortions and error estimation. Int. J. Numer. Methods Eng. 28:1487–1504, 1989.CrossRefGoogle Scholar
  6. 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.PubMedCentralPubMedCrossRefGoogle Scholar
  7. 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.PubMedCrossRefGoogle Scholar
  8. 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.PubMedCrossRefGoogle Scholar
  9. 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.PubMedCrossRefGoogle Scholar
  10. 10.
    Garg, S., and P. W. Serruys. Coronary stents: looking forward. J. Am. Coll. Cardiol. 56:S43–S78, 2010.PubMedCrossRefGoogle Scholar
  11. 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.PubMedCrossRefGoogle Scholar
  12. 12.
    Gunn, J., and D. Cumberland. Stent coatings and local drug delivery—state of the art. Eur. Heart J. 20:1693–1700, 1999.PubMedCrossRefGoogle Scholar
  13. 13.
    Gunn, J., and D. Cumberland. Does stent design influence restenosis? Eur. Heart J. 20:1009–1013, 1999.PubMedCrossRefGoogle Scholar
  14. 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.PubMedGoogle Scholar
  15. 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.PubMedCentralPubMedCrossRefGoogle Scholar
  16. 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.PubMedCrossRefGoogle Scholar
  17. 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.PubMedCrossRefGoogle Scholar
  18. 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.PubMedGoogle Scholar
  19. 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.CrossRefGoogle Scholar
  20. 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.CrossRefGoogle Scholar
  21. 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.CrossRefGoogle Scholar
  22. 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.PubMedGoogle Scholar
  23. 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.PubMedGoogle Scholar
  24. 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.CrossRefGoogle Scholar
  25. 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.PubMedCrossRefGoogle Scholar
  26. 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.PubMedCrossRefGoogle Scholar
  27. 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.PubMedCrossRefGoogle Scholar
  28. 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.PubMedCrossRefGoogle Scholar
  29. 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.PubMedCrossRefGoogle Scholar
  30. 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.PubMedCrossRefGoogle Scholar
  31. 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.PubMedCrossRefGoogle Scholar
  32. 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.CrossRefGoogle Scholar
  33. 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.PubMedCrossRefGoogle Scholar
  34. 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.PubMedCentralPubMedCrossRefGoogle Scholar
  35. 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.CrossRefGoogle Scholar
  36. 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. 37.
    Schneider, D. B., and D. A. Dichek. Intravascular stent endothelialization. A goal worth pursuing? Circulation 95:308–310, 1997.PubMedCrossRefGoogle Scholar
  38. 38.
    Sethi, R., and C. H. Lee. Endothelial progenitor cell capture stent: safety and effectiveness. J. Interv. Cardiol. 25:493–500, 2012.PubMedCrossRefGoogle Scholar
  39. 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.PubMedGoogle Scholar
  40. 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.CrossRefGoogle Scholar
  41. 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.CrossRefGoogle Scholar
  42. 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.PubMedCrossRefGoogle Scholar

Copyright information

© Biomedical Engineering Society 2014

Authors and Affiliations

  • Susheil Uthamaraj
    • 1
  • Brandon J. Tefft
    • 2
  • Martin Klabusay
    • 3
  • Ota Hlinomaz
    • 4
  • Gurpreet S. Sandhu
    • 2
    • 5
  • Dan Dragomir-Daescu
    • 1
    • 5
    Email author
  1. 1.Division of EngineeringMayo ClinicRochesterUSA
  2. 2.Division of Cardiovascular DiseasesMayo ClinicRochesterUSA
  3. 3.Integrated Center of Cellular Therapy and Regenerative Medicine, ICRCSt. Anne’s University HospitalBrnoCzech Republic
  4. 4.Department of Cardioangiology, ICRCSt. Anne’s University HospitalBrnoCzech Republic
  5. 5.Mayo Clinic College of MedicineRochesterUSA

Personalised recommendations