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. 2023 Oct;15(10):1001-1006.
doi: 10.1136/jnis-2022-019248. Epub 2022 Sep 30.

Poly(2-methoxyethyl acrylate) (PMEA) improves the thromboresistance of FRED flow diverters: a thrombogenic evaluation of flow diverters with human blood under flow conditions

Keiko Yoshizawa  1 , Hirohisa Kobayashi  2 , Atsushi Kaneki  2 , Mika Takenouchi  2 , John Belletto  3 , Aaron Baldwin  4 , Takao Anzai  1
Affiliations

Poly(2-methoxyethyl acrylate) (PMEA) improves the thromboresistance of FRED flow diverters: a thrombogenic evaluation of flow diverters with human blood under flow conditions

Keiko Yoshizawa et al. J Neurointerv Surg. 2023 Oct.

Abstract

Background: Surface modification of flow-diverting stents has been explored to reduce thrombus-related complications that may arise under clinical use. This study investigated the thromboresistant properties of the flow redirection endoluminal device (FRED) X, a flow diverter treated with a copolymer of poly(2-methoxyethyl acrylate) (PMEA; X Technology).

Methods: The performance of FRED, FRED X, and Pipeline Flex with Shield Technology (sPED) was evaluated in an in vitro blood loop model. Blood activation level was assessed by the concentration of thrombin-antithrombin complex (TAT), β-thromboglobulin (β-TG), and platelet count, and qualitatively by scanning electron microscopy (SEM). Cellular adhesion characteristics were measured using human aortic endothelial cells that were seeded on flat sheets mimicking the surface of FRED, FRED X, and sPED, and evaluated with fluorescence microscopy. Statistical comparisons were conducted using one-way analysis of variance (ANOVA) with Tukey post hoc tests.

Results: FRED X, sPED, and control blood loops showed significantly reduced blood activation levels (TAT and β-TG) compared with FRED (p<0.01). Consequently, FRED showed a significant decrease in platelet count compared with FRED X, sPED, and control loops (p<0.01). SEM imaging showed the lowest accumulation of blood cell-like deposits on FRED X compared with sPED and FRED, while FRED had the highest accumulation. Endothelial cells adhered and were widely spread on X Technology-treated sheets, while minimal cell adhesion was observed on phosphorylcholine-treated sheets.

Conclusion: The X Technology surface modification of FRED X demonstrated superior thromboresistant properties over untreated FRED while maintaining comparable cellular adhesion. Taken together, these properties may help mitigate material-related thromboembolic complications.

Keywords: Aneurysm; Blood Flow; Device; Flow Diverter; Stent.

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Conflict of interest statement

Competing interests: KY, HK, AK, MT, and TA are employees of Terumo Co., Ltd. AB and JB are employees of MicroVention Inc.

Figures

Figure 1
Figure 1
Blood activation after circulation. (A) Thrombin-antithrombin complex (TAT). (B) β-thromboglobulin (β-TG). (C) Platelet count. *Indicates no significant difference compared with the negative control levels based on the post-hoc Tukey analysis (adjusted p>0.8). **Indicates a significant difference between the negative control and other loops based on the post-hoc Tukey analysis (adjusted p<0.01). FRED, flow redirection endoluminal device; FRED X, FRED with X Technology; sPED, Pipeline Flex with Shield Technology.
Figure 2
Figure 2
Representative scanning electron microscopy observations after blood circulation for one donor. (A) Flow redirection endoluminal device (FRED). (B) FRED X. (C) Pipeline Flex with Shield Technology (sPED). Scale bars: 100 μm.
Figure 3
Figure 3
Fluorescence microscopy visualization of adhesion spot formation on samples. (A) Electropolished nickel titanium sheet (NiTi). (B) Electropolished NiTi sheet treated with X Technology (NiTi X). (C) Unadulterated polyethylene terephthalate sheet treated with 2-methacryloyloxyethyl phosphorylcholine (PET MPC). (D) Unadulterated PET sheet (PET). (E) Unadulterated PET sheet treated with X Coating (PET X). Red, vinculin; green, actin; blue, nucleus; white triangles, desmosomes associated with vinculin accumulation. Scale bars 20 μm.
Figure 4
Figure 4
Number of endothelial cells adhered to each sample. MPC, 2-methacryloyloxyethyl phosphorylcholine; NiTi, nickel titanium; PET, polyethylene terephthalate.
See this image and copyright information in PMC

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