Hydrophilic Stent Coating Inhibits Platelet Adhesion on Stent Surfaces: Initial Results In Vitro

Abstract

Background: Endovascular stents and flow diverter stents (FDS) have revolutionized the treatment of intradural aneurysms; however, the need for dual anti-platelet treatment (DAPT) limits their use and can cause additional issues. Therefore, there is a need to develop stent coatings that negate the need for DAPT.

Methods: Two different hydrophilic polymer coatings (HPC-I and HPC-II) were used to coat small nickel titanium plates to initially test the hydrophilic properties of these coatings when applied to nickel titanium. The plates were subsequently incubated with non-medicated whole blood from healthy volunteers for 10 min and stained with a CD61 immunofluorescent antibody that allows detection of adherent platelets. The coatings were applied to FDS wires and were again incubated with non-medicated whole blood from the same volunteers. Scanning electron microscopy was used to detect adherent platelets on the wire surface.

Results: The HPC-II coating (1.12 ± 0.4%) showed a significantly lower CD61 +ve cell count (p ≤ 0.001) compared to both uncoated NiTi plates (48.61 ± 7.3%) and those with the HPC-I coating (mean 40.19 ± 8.9%). Minimal adherent platelets were seen on the FDS nickel titanium wires coated with the HPC-II compared to uncoated FDS under electron microscopy.

Conclusion: There is a significant decrease in the number of adherent CD61 +ve platelets on nickel titanium surfaces coated with the HPC-II coating compared to uncoated surfaces. The coating can be successfully applied to the wires of flow diverters. The results of this study are promising with regard to the development of new anti-thrombogenic endovascular devices.

Keywords: Anti-platelet; Anti-thrombogenic coating; Flow diverter stent.

Conflict of interest statement

Conflict of interest

TLH is employed in the R&D department of phenox. PB is a consultant and proctor for phenox and Neurvana Medical. MP, AB declared no conflict of interests. RMM is a consultant and proctor for phenox. HH is a co-founder and shareholder of phenox. HM is a co-founder, shareholder and CEO of phenox.

Ethical Statement

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

Figures

Fig. 1

Comparison of the hydrophilic properties of uncoated (A, B) and hydrophilic-coated (C, D) nickel titanium plates and braided flow diverter stents. After application of H2O droplets on the uncoated specimens, the droplets remain in spherical shape on the surface of the specimens (A, B; arrows). Application of the same amount of water on the hydrophilic-coated specimens (HPC-II shown exemplarily) leads to a complete wetting of the sample (C, D)

Fig. 2

Representative fluorescence micrographs of uncoated (bare) and differently coated (HPC-I and HPC-II) nickel titanium specimens. The specimens were incubated in whole blood for 10 min under dynamic conditions. Adherent platelets were stained with a CD61 antibody (yellow fluorescence). Bottom right: Quantitative Phase Analysis of the area coated with CD61-positive cells from experiments with ten different donors (mean ± SEM, asterisks denote significance at p ≤ 0.05; ***p ≤ 0.001; Kruskal–Wallis and DUNN post-test; sample size HPC-I vs. bare, n = 5; sample size HPC-II vs. bare, n = 15)

Fig. 3

Representative fluorescence micrographs of uncoated (bare) and HPC-II-coated p64 flow diverter stents. The specimens were incubated in whole blood for 10 min under dynamic conditions. Adherent platelets were stained with a CD61 antibody (yellow fluorescence). The uncoated (bare) flow diverter stent is completely covered with adherent platelets, whereas only very few cells could be detected on the HPC-II-coated specimen. Again, HPC-II coating nearly completely prevents adherence of platelets even on the braided flow diverter stent

Fig. 4

SEM micrographs of uncoated (bare) and HPC-II-coated p48 flow diverter stents. The specimens were incubated in whole blood for 10 min under dynamic conditions. Stents and adherent cells were fixed and sputtered with gold. The rectangle in the upper row indicates the area shown in a higher magnification below