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Long-term preclinical evaluation of bioabsorbable polymer-coated drug-eluting stent in a porcine model

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Abstract

Bioabsorbable polymer-based drug-eluting stents have been shown to be effective and safe in the actual practice. The objective of the present study was to evaluate a biodegradable poly-L-lactic acid (PLLA)-based sirolimus-coated stent in comparison with a commercial everolimus-eluting stent with a permanent polymer in a porcine coronary restenosis model on a short-, mid-, and long-term basis. Pigs were randomized into eight groups in which the coronary arteries (36 pigs with 72 coronary arteries) had either a sirolimus-eluting stent with PLLA (SES, n=24, follow-up after 4, 12, and 24 weeks), bare metal stent (BMS, n=12, follow-up after 4 weeks), PLLA-coated stent without a drug (PCS, n=12, follow-up after 4 weeks), or commercial everolimus-eluting stent with a permanent polymer (EES, Promus PREMIER®, n=24, follow-up after 4, 12, and 24 weeks). Histopathological analysis was performed at 4, 12, or 24 weeks after stenting. The surface morphology of the SES, visualized using an optical microscope and a scanning electron microscope, was smooth and uniform with virtually no defects. Sirolimus was released slowly over 60 days. There was no significant difference in the percent area stenosis between the SES and EES at any of the follow-up time points (13.0±8.10% in SES vs. 14.1±9.12% in EES at 4 weeks, 23.1±8.63% in SES vs. 21.3±7.92% in EES at 12 weeks, 28.2±8.20% in SES vs. 25.1±8.51% in EES at 24 weeks, each p=NS). The percent area stenosis using micro-computed tomography and intravenous ultrasound demonstrated similar restenosis rates with histopathological stenosis between the SES and EES. The SES with a biodegradable polymer was as effective as the commercial EES with a permanent polymer in inhibiting neointima proliferation at 4, 12, and 24 weeks in a porcine coronary restenosis model.

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References

  1. C. Stettler, S. Wandel, S. Allemann, A. Kastrati, M. C. Morice, A. Schomig, M. E. Pfisterer, G. W. Stone, M. B. Leon, J. S. de Lezo, J. J. Goy, S. J. Park, M. Sabate, M. J. Suttorp, H. Kelbaek, C. Spaulding, M. Menichelli, P. Vermeersch, M. T. Dirksen, P. Cervinka, A. S. Petronio, A. J. Nordmann, P. Diem, B. Meier, M. Zwahlen, S. Reichenbach, S. Trelle, S. Windecker, and P. Juni, Lancet, 370, 937 (2007).

    Article  CAS  Google Scholar 

  2. G. W. Stone, J. W. Moses, S. G. Ellis, J. Schofer, K. D. Dawkins, M. C. Morice, A. Colombo, E. Schampaert, E. Grube, A. J. Kirtane, D. E. Cutlip, M. Fahy, S. J. Pocock, R. Mehran, and M. B. Leon, N. Engl. J. Med., 356, 998 (2007).

  3. M. Joner, A. V. Finn, A. Farb, E. K. Mont, F. D. Kolodgie, E. Ladich, R. Kutys, K. Skorija, H. K. Gold, and R. Virmani, J. Am. Coll. Cardiol., 48, 193 (2006).

  4. S. Cook, E. Ladich, G. Nakazawa, P. Eshtehardi, M. Neidhart, R. Vogel, M. Togni, P. Wenaweser, M. Billinger, C. Seiler, S. Gay, B. Meier, W. J. Pichler, P. Juni, R. Virmani, and S. Windecker, Circulation, 120, 391 (2009).

    Article  Google Scholar 

  5. G. Nakazawa, A. V. Finn, M. Joner, E. Ladich, R. Kutys, E. K. Mont, H. K. Gold, A. P. Burke, F. D. Kolodgie, and R. Virmani, Circulation, 118, 1138 (2008).

    Article  Google Scholar 

  6. A. Kastrati, J. Mehilli, J. Dirschinger, F. Dotzer, H. Schuhlen, F. J. Neumann, M. Fleckenstein, C. Pfafferott, M. Seyfarth, and A. Schomig, Vestn. Rentgenol. Radiol., 2, 52 (2012).

    Google Scholar 

  7. J. Pache, 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, J. Am. Coll. Cardiol., 41, 1283 (2003).

    Article  Google Scholar 

  8. F. Rossi, T. Casalini, E. Raffa, M. Masi, and G. Perale, Mol. Pharm., 9, 1898 (2012).

    Article  CAS  Google Scholar 

  9. A. Strohbach and R. Busch, Int. J. Polym. Sci., 2015, Article ID 782653 (2015).

    Google Scholar 

  10. H. Tamai, K. Igaki, E. Kyo, K. Kosuga, A. Kawashima, S. Matsui, H. Komori, T. Tsuji, S. Motohara, and H. Uehata, Circulation, 102, 399 (2000).

    Article  CAS  Google Scholar 

  11. S. Nishio, K. Kosuga, K. Igaki, M. Okada, E. Kyo, T. Tsuji, E. Takeuchi, Y. Inuzuka, S. Takeda, T. Hata, Y. Takeuchi, Y. Kawada, T. Harita, J. Seki, S. Akamatsu, S. Hasegawa, N. Bruining, S. Brugaletta, S. de Winter, T. Muramatsu, Y. Onuma, P. W. Serruys, and S. Ikeguchi, Circulation, 125, 2343 (2012).

    Article  CAS  Google Scholar 

  12. I. H. Bae, K. S. Lim, J. K. Park, D. S. Park, S. Y. Lee, E. J. Jang, M. S. Ji, D. S. Sim, Y. J. Hong, Y. Ahn, J. C. Park, J. G. Cho, J. C. Kang, I. S. Kim, J. W. Nah, and M. H. Jeong, J. Ind. Eng. Chem., 21, 1295 (2015).

    Article  CAS  Google Scholar 

  13. K. S. Lim, I. H. Bae, J. H. Kim, D. S. Park, J. M. Kim, J. H. Kim, D. S. Sim, Y. J. Hong, and M. H. Jeong, Chonnam Med. J., 49, 7 (2013).

    Article  CAS  Google Scholar 

  14. X. Ma, S. Oyamada, F. Gao, T. Wu, M. P. Robich, H. Wu, X. Wang, B. Buchholz, S. McCarthy, Z. Gu, C. F. Bianchi, F. W. Sellke, and R. Laham, J. Pharm. Biomed. Anal., 54, 807 (2011).

  15. R. S. Schwartz, K. C. Huber, J. G. Murphy, W. D. Edwards, A. R. Camrud, R. E. Vlietstra, and D. R. Holmes, J. Am. Coll. Cardiol., 19, 267 (1992).

    Article  CAS  Google Scholar 

  16. H. L. Che, I. H. Bae, K. S. Lim, I. T. Song, H. Lee, M. Muthiah, R. Namgung, W. J. Kim, D. G. Kim, Y. Ahn, M. H. Jeong, and I. K. Park, Biomaterials, 33, 8548 (2012).

    Article  CAS  Google Scholar 

  17. R. S. Schwartz, E. Edelman, R. Virmani, A. Carter, J. F. Granada, G. L. Kaluza, N. A. Chronos, K. A. Robinson, R. Waksman, J. Weinberger, G. J. Wilson, and R. L. Wilensky, Circ. Cardiovasc. Interv., 1, 143 (2008).

    Article  Google Scholar 

  18. T. Suzuki, G. Kopia, S. Hayashi, L. R. Bailey, G. Llanos, R. Wilensky, B. D. Klugherz, G. Papandreou, P. Narayan, M. B. Leon, A. C. Yeung, F. Tio, P. S. Tsao, R. Falotico, and A. J. Carter, Circulation, 104, 1188 (2001).

    Article  CAS  Google Scholar 

  19. F. Otsuka, Q. Cheng, K. Yahagi, E. Acampado, A. Sheehy, S. K. Yazdani, K. Sakakura, K. Euller, L. E. Perkins, F. D. Kolodgie, R. Virmani, and M. Joner, JACC Cardiovasc. Interv., 8, 1248 (2015).

    Article  Google Scholar 

  20. H. Ben Salem, M. Kamoun, H. Khaldi, K. Ghannem, S. Majadla, M. Ghannem, and S. Godard, Ann. Cardiol. Angeiol. (Paris), 61, 64 (2012).

    Article  CAS  Google Scholar 

  21. R. Virmani, F. D. Kolodgie, A. Farb, and A. Lafont, Heart, 89, 133 (2003).

    Article  CAS  Google Scholar 

  22. R. Mehran, G. Dangas, A. S. Abizaid, G. S. Mintz, A. J. Lansky, L. F. Satler, A. D. Pichard, K. M. Kent, G. W. Stone, and M. B. Leon, Circulation, 100, 1872 (1999).

    Article  CAS  Google Scholar 

  23. C. Schulz, R. A. Herrmann, C. Beilharz, J. Pasquantonio, and E. Alt, Heart, 83, 462 (2000).

    Article  CAS  Google Scholar 

  24. D. S. Sim, M. H. Jeong, D. S. Park, J. H. Kim, K. S. Lim, I. H. Bae, P. Zhehao, H. Y. Yang, J. H. Lee, D. Y. Hyun, Y. J. Hong, J. H. Kim, Y. Ahn, and J. C. Kang, Int. J. Cardiol., 222, 436 (2016).

    Article  Google Scholar 

  25. H. L. Che, I. H. Bae, K. S. Lim, I. T. Song, H. Lee, D. Lee, W. J. Kim, M. H. Jeong, and Y. Ahn, J. Biomed. Nanotechnol., 12, 1211 (2016).

    Article  CAS  Google Scholar 

  26. K. S. Lim, J. K. Park, M. H. Jeong, I. H. Bae, J. W. Nah, D. S. Park, J. M. Kim, J. H. Kim, S. Y. Lee, E. J. Jang, S. Jang, H. K. Kim, D. S. Sim, K. H. Park, Y. J. Hong, Y. Ahn, and J. C. Kang, J. Mater. Sci. Mater. Med., 27, 66 (2016).

    Article  Google Scholar 

  27. S. Y. Lee, I. H. Bae, D. Sung Park, E. J. Jang, J. W. Shim, K. S. Lim, J. K. Park, D. S. Sim, and M. H. Jeong, J. Biomater. Appl., 31, 36 (2016).

    Article  CAS  Google Scholar 

  28. H. L. Che, I. H. Bae, K. S. Lim, S. Uthaman, I. T. Song, H. Lee, D. Lee, W. J. Kim, Y. Ahn, I. K. Park, and M. H. Jeong, Korean Circ. J., 46, 23 (2016).

    Article  Google Scholar 

  29. E. J. Jang, I. H. Bae, D. S. Park, S. Y. Lee, K. S. Lim, J. K. Park, J. W. Shim, D. S. Sim, and M. H. Jeong, J. Mater. Sci. Mater. Med., 26, 251 (2015).

    Article  Google Scholar 

  30. J. K. Park, K. S. Lim, I. H. Bae, J. P. Nam, J. H. Cho, C. Choi, J. W. Nah, and M. H. Jeong, J. Mech. Behav. Biomed. Mater., 53, 68 (2016).

    Article  Google Scholar 

  31. K. S. Lim, M. H. Jeong, I. H. Bae, J. K. Park, D. S. Park, J. M. Kim, J. H. Kim, H. S. Kim, Y. S. Kim, H. Y. Jeong, S. J. Song, E. J. Yang, D. L. Cho, D. S. Sim, K. H. Park, Y. J. Hong, and Y. Ahn, J. Cardiol., 64, 409 (2014).

    Article  Google Scholar 

  32. K. S. Lim, M. H. Jeong, I. H. Bae, J. K. Park, D. S. Park, J. M. Kim, J. H. Kim, D. L. Cho, D. S. Sim, K. H. Park, Y. J. Hong, and Y. Ahn, Chonnam. Med. J., 49, 118 (2013).

    Article  CAS  Google Scholar 

  33. J. S. Kwon, S. J. Song, E. J. Yang, Y. S. Kim, K. S. Lim, D. G. Kim, D. L. Cho, M. H. Jeong, and Y. Ahn, Int. J. Cardiol., 168, 5104 (2013).

    Article  Google Scholar 

  34. Y. J. Hong, M. H. Jeong, S. J. Song, D. S. Sim, J. H. Kim, K. S. Lim, D. Hachinohe, K. Ahmed, S. H. Hwang, M. G. Lee, J. S. Ko, K. H. Park, H. J. Yoon, N. S. Yoon, K. H. Kim, H. W. Park, J. H. Kim, Y. Ahn, J. G. Cho, D. L. Cho, J. C. Park, and J. C. Kang, Korean Circ. J., 41, 535 (2011).

    Article  CAS  Google Scholar 

  35. K. S. Lim, Y. J. Hong, D. Hachinohe, K. Ahmed, M. H. Jeong, J. H. Kim, D. S. Sim, M. G. Lee, K. H. Park, J. H. Kim, Y. Ahn, J. G. Cho, J. C. Park, S. J. Song, K. W. Jung, D. L. Cho, and J. C. Kang, Korean Circ. J., 41, 241 (2011).

    Article  CAS  Google Scholar 

  36. G. Guagliumi, H. Ikejima, V. Sirbu, H. Bezerra, G. Musumeci, N. Lortkipanidze, L. Fiocca, S. Tahara, A. Vassileva, A. Matiashvili, O. Valsecchi, and M. Costa, JACC Cardiovasc. Interv., 4, 778 (2011).

    Article  Google Scholar 

  37. E. Grube, S. Sonoda, F. Ikeno, Y. Honda, S. Kar, C. Chan, U. Gerckens, A. J. Lansky, and P. J. Fitzgerald, Circulation, 109, 2168 (2004).

    Article  CAS  Google Scholar 

  38. S. J. Park, Y. H. Kim, B. K. Lee, S. W. Lee, C. W. Lee, M. K. Hong, J. J. Kim, G. S. Mintz, and S. W. Park, J. Am. Coll. Cardiol., 45, 351 (2005).

    Article  CAS  Google Scholar 

  39. T. Kimura, T. Morimoto, Y. Nakagawa, K. Kawai, S. Miyazaki, T. Muramatsu, N. Shiode, M. Namura, T. Sone, S. Oshima, H. Nishikawa, Y. Hiasa, Y. Hayashi, M. Nobuyoshi, K. Mitudo, and J.-C. R. Investigators, Circulation, 125, 584 (2012).

    Article  CAS  Google Scholar 

  40. L. Raber, L. Wohlwend, M. Wigger, M. Togni, S. Wandel, P. Wenaweser, S. Cook, A. Moschovitis, R. Vogel, B. Kalesan, C. Seiler, F. Eberli, T. F. Luscher, B. Meier, P. Juni, and S. Windecker, Circulation, 123, 2819 (2011).

    Article  Google Scholar 

  41. E. L. Eisenstein, M. B. Leon, D. E. Kandzari, L. Mauri, R. Edwards, D. F. Kong, P. A. Cowper, K. J. Anstrom, and E. I. Investigators, JACC Cardiovasc. Interv., 2, 1199 (2009).

    Article  Google Scholar 

  42. D. E. Kandzari, L. Mauri, J. J. Popma, M. A. Turco, P. A. Gurbel, P. J. Fitzgerald, and M. B. Leon, JACC Cardiovasc. Interv., 4, 543 (2011).

    Article  Google Scholar 

  43. L. Raber, M. Magro, G. G. Stefanini, B. Kalesan, R. T. van Domburg, Y. Onuma, P. Wenaweser, J. Daemen, B. Meier, P. Juni, P. W. Serruys, and S. Windecker, Circulation, 125, 1110 (2012).

    Article  Google Scholar 

  44. A. Farb, A. P. Burke, F. D. Kolodgie, and R. Virmani, Circulation, 108, 1701 (2003).

    Article  Google Scholar 

  45. P. Lanzer, K. Sternberg, K. P. Schmitz, F. Kolodgie, G. Nakazawa, and R. Virmani, Herz, 33, 334 (2008).

    Article  Google Scholar 

  46. R. A. Byrne, J. Mehilli, R. Iijima, S. Schulz, J. Pache, M. Seyfarth, A. Schomig, and A. Kastrati, Eur. Heart J., 30, 923 (2009).

    Article  CAS  Google Scholar 

  47. S. Cassese, M. Fusaro, R. A. Byrne, T. Tada, P. Hoppmann, M. Joner, K. L. Laugwitz, H. Schunkert, and A. Kastrati, Int. J. Cardiol., 175, 484 (2014).

    Article  Google Scholar 

  48. M. Sabate, L. Raber, D. Heg, S. Brugaletta, H. Kelbaek, A. Cequier, M. Ostojic, A. Iniguez, D. Tuller, A. Serra, A. Baumbach, C. von Birgelen, R. Hernandez-Antolin, M. Roffi, V. Mainar, M. Valgimigli, P. W. Serruys, P. Juni, and S. Windecker, JACC Cardiovasc. Int., 7, 55 (2014).

    Article  Google Scholar 

  49. T. Palmerini, G. Biondi-Zoccai, D. Della Riva, A. Mariani, M. Sabate, P. C. Smits, C. Kaiser, F. D’Ascenzo, G. Frati, M. Mancone, P. Genereux, and G. W. Stone, J. Am. Coll. Cardiol., 63, 299 (2014).

    Article  CAS  Google Scholar 

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  1. These authors equally contributed to this work.

Authors and Affiliations

  1. Korea Cardiovascular Stent Institute, Jangsung, Jeonnam, 57248, Korea

    Kyung Seob Lim, Myung Ho Jeong & In Ho Bae

  2. Cardiovascular Convergence Research Center, Nominated by the Korea Ministry of Health and Welfare, Gwangju, 61469, Korea

    Kyung Seob Lim, Myung Ho Jeong, In Ho Bae, Dae Sung Park, Jae Won Shim, Jung Ha Kim, Hyun Kuk Kim, Sung Soo Kim, Doo Sun Sim, Young Joon Hong, Ju Han Kim & Youngkeun Ahn

  3. Cardiovascular Research Center, Chonnam National University Hospital, Gwangju, 61469, Korea

    Kyung Seob Lim, Myung Ho Jeong, Dae Sung Park, Jae Won Shim, Jung Ha Kim, Hyun Kuk Kim, Sung Soo Kim, Doo Sun Sim, Young Joon Hong, Ju Han Kim & Youngkeun Ahn

  4. Regeneromics Research Center, Chonnam National University, Gwangju, 61469, Korea

    Myung Ho Jeong

  5. Department of Polymer Science and Engineering, Sunchon National University, Sunchon, Jeonnam, 57940, Korea

    Jae-Woon Nah

  6. CGBio. Co. Ltd, Jangseong-gun, Jeonnam, 57248, Korea

    Jun-Kyu Park

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  1. Kyung Seob Lim
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Correspondence to Myung Ho Jeong.

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Acknowledgments: This study was supported by grants from the Korean Health Technology R&D Project (HI13C1527, HI16C0094), Ministry of Health & Welfare, Republic of Korea; the Cardiovascular Research Center, Chonnam National University Hospital; and the Pioneer Research Center Program through the National Research Foundation of Korea funded by the Ministry of Education, Science and Technology (NRF- 2014M3C1A3056052).

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Lim, K.S., Park, JK., Jeong, M.H. et al. Long-term preclinical evaluation of bioabsorbable polymer-coated drug-eluting stent in a porcine model. Macromol. Res. 25, 730–738 (2017). https://doi.org/10.1007/s13233-017-5067-z

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