J Korean Med Sci.  2021 Oct;36(40):e259. 10.3346/jkms.2021.36.e259.

Preclinical Evaluation of a Novel Polymer-free Everolimus-eluting Stent in a Mid-term Porcine Coronary Restenosis Model

• Cho KH
• Jeong MH
• Park DS
• Kim M
• Kim J
• Park JK
• Han X
• Hyun DY
• Kim MC
• Sim DS
• Hong YJ
• Kim JH
• Ahn Y

• KMID: 2521426
• DOI: http://doi.org/10.3346/jkms.2021.36.e259

Abstract

Background
Titanium dioxide films exhibit good biocompatibility and may be effective as drug-binding matrices for drug-eluting stents. We conducted a mid-term evaluation of a novel polymer-free everolimus-eluting stent using nitrogen-doped titanium dioxide film deposition (TIGEREVOLUTION^® ) in comparison with a commercial durable polymer everolimus-eluting stent (XIENCE Alpine^® ) in a porcine coronary restenosis model.
Methods
Twenty-eight coronary arteries from 14 mini-pigs were randomly allocated to TIGEREVOLUTION^® stent and XIENCE Alpine^® stent groups. The stents were implanted in the coronary artery at a 1.1–1.2:1 stent-to-artery ratio. Eleven stented coronary arteries in each group were finally analyzed using coronary angiography, optical coherence tomography, and histopathologic evaluation 6 months after stenting.
Results
Quantitative coronary analysis showed no significant differences in the preprocedural, post-procedural, and 6-month lumen diameters between the groups. In the volumetric analysis of optical coherence tomography at 6 months, no significant differences were observed in stent volume, lumen volume, and percent area stenosis between the groups. There were no significant differences in injury score, inflammation score, or fibrin score between the groups, although the fibrin score was zero in the TIGEREVOLUTION^® stent group (0 vs. 0.07 ± 0.11, P = 0.180).
Conclusion
Preclinical evaluation, including optical coherence tomographic findings 6 months after stenting, demonstrated that the TIGEREVOLUTION^® stent exhibited efficacy and safety comparable with the XIENCE Alpine^® stent, supporting the need for further clinical studies on the TIGEREVOLUTION^® stent.

Keyword

Drug-eluting Stents; Polymers; Swine; Titanium Dioxide; Optical Coherence Tomography

Figure

• 

  Fig. 1 Configuration and structure of the TIGEREVOLUTION® stent. (A) The TIGEREVOLUTION® stent mounted on the balloon. (B) After balloon inflation. (C) Schematic structure of the connector. (D) Schematic cross-section of the strut.TiO2 = titanium dioxide, Co-Cr = cobalt-chromium.

• 

  Fig. 2 Study scheme.N = nitrogen, TiO2 = titanium dioxide, EES = everolimus-eluting stent, LAD = left anterior descending artery, LCX = left circumflex artery, RCA = right coronary artery, QCA = quantitative coronary analysis, OCT = optical coherence tomography.

• 

  Fig. 3 In vitro cumulative release kinetics of everolimus from the stent. The indicated values are the mean ± standard deviation (n = 10).TiO2 = titanium dioxide, PLGA = poly(lactic-co-glycolic acid).Reprinted from Int J Cardiol 2016;222:436-440 with permission from Elsevier.

• 

  Fig. 4 Efficacy of the TIGEREVOLUTION® stent. Coronary angiographic images of the TIGEREVOLUTION® stent (A) pre-implantation, (B) during implantation, (C) post-implantation, and (D) at the 6-month follow-up. Coronary angiographic images of the XIENCE Alpine® stent (E) pre-implantation, (F) during implantation, (G) post-implantation, and (H) at the 6-month follow-up. OCT images of the TIGEREVOLUTION® stent (I) post-implantation and (J) at the 6-month follow-up. OCT images of the XIENCE Alpine® stent (K) post-implantation and (L) at the 6-month follow-up. Volumetric analysis of the OCT images at the 6-month follow-up: (M) stent volume, (N) lumen volume, and (O) percentage area stenosis. The box displays the median value with an interquartile range. The black points represent mean values.OCT = optical coherence tomographic.

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  Fig. 5 Histopathologic analysis at the 6-month follow-up. Representative photomicrographs of hematoxylin and eosin staining of the TIGEREVOLUTION® stent (A: magnitude × 20) and XIENCE Alpine® stent (D: magnitude × 20), and high-power images (B and E: magnitude × 200). Carstairs' fibrin stain of the TIGEREVOLUTION® stent (C) and the XIENCE Alpine® stent (F) (magnitude × 20). Injury score (G), inflammation score (H), and intimal fibrin score (I). The box displays the median value with an interquartile range. The black points represent the mean values.

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  Fig. 6 Endothelialization evaluation of the TIGEREVOLUTION® stent and the XIENCE Alpine® stent at the 6-month follow-up. (A) Immunohistochemical staining of CD31 (bright green positive cells) and DAPI (magnitude x 100). (B) Percentage of CD31 coverage of the TIGEREVOLUTION® stent and the XIENCE Alpine® stent. The box displays the median value with the interquartile range. The black point displays the mean value.CD31 = cluster of differentiation; DAPI = 4′,6 diamidino-2-phenylindole.

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