(G-253) Effect of Plasma Nanocoatings onto Cobalt Chromium L605 Alloy for Cardiovascular Stent Applications

Introduction:
Stents are medical devices that act as scaffolds to open narrowed arteries and restore normal blood flow to the heart. The lack of endothelium and inflammatory responses in vessel walls due to artery damage during stent implantation stimulates smooth muscle cell (SMC) proliferation and migration, leading to in-stent restenosis rates of as high as 20–30% in bare metal stents (BMSs).
The drug eluting stent (DES) has become the most used stent due to its capacity to release cytostatic drugs, such as everolimus, that inhibit SMC proliferation and in-stent restenosis. However, the remaining problem with DES is in-stent thrombosis, resulting from concomitant inhibition of endothelial cell proliferation and migration, delayed recovery of an intact endothelium, and consequently promoting activation of blood platelets and the clotting cascade by prothrombotic subendothelial molecules.
The objective of this study was to evaluate the biocompatibility of trimethylsilane (TMS) plasma nanocoatings modified with NH3/O2 (2:1 molar ratio) plasma post-treatment onto cobalt chromium (CoCr) L605 alloy coupons and stents for cardiovascular stent applications.


Materials and Methods:
Circular coupons, 15 mm in diameter, were sectioned from CoCr L605 alloy sheets (AMS 5537). After cleaning and drying at room temperature, the L605 coupons were coated with TMS plasma nanocoating, denoted as 'TMS.' Subsequently, the 'TMS' samples underwent plasma post-treatment using NH3/O2, designated as 'TMS+NH3/O2”.
The thickness of the plasma nanocoating on L605 coupons was determined using a microscope-mounted thin-film measurement technique. Evaluation of the plasma nanocoatings included assessments of: 1) Coating adhesion, conducted through both tape tests and scanning electron microscopy (SEM), 2) Corrosion behavior, analyzed via open circuit potential (OCP) and cyclic polarization tests, 3) Ion release, in accordance with ISO 10993-5 and ISO 10993-12 standards, 4) Cell proliferation, measured using Porcine Artery Coronary Endothelial Cells (PCAECs) and Porcine Coronary Artery Smooth Muscle Cells (PCASMCs) with an automated cell counter (Countess), 5) Surface chemistry, examined through X-ray photoelectron spectroscopy (XPS), and 6) Wettability, determined by contact angle measurements. These comprehensive studies were conducted to gain insights into how surface properties influence the biocompatibility of plasma nanocoatings.


Results and Discussion:
The results demonstrate that NH3/O2 post-treated TMS plasma nanocoatings exhibit hydrophilic properties, as indicated by a water contact angle of 48.5°. Additionally, their surface composition typically comprises O (39.39 at.%), Si (31.92 at.%), C (24.12 at.%), and N (2.77 at.%). These plasma nanocoatings conformed precisely to the substrate surface topography and displayed exceptional adhesion to the alloy substrates, as confirmed by a tape test (ASTM D3359). Importantly, there were no signs of cracking or peeling from the L605 stent surfaces even after dilation.
The plasma nanocoatings also improve the corrosion resistance of CoCr L605 alloy by increasing corrosion potential and decreasing corrosion rates with no pitting corrosion and no mineral adsorption layer. Ion releasing test revealed that Co, Cr, and Ni ion concentrations were reduced by 64–79%, 67–69%, and 57–72%, respectively, in the plasma-nanocoated L605 samples as compared to uncoated L605 control samples.
Seven-day cell culture demonstrated that, in comparison with the uncoated L605 control surfaces, the plasma nanocoating surfaces showed 62 ± 7.3% decrease in porcine coronary artery smooth muscle cells (PCASMCs) density and had comparable density of porcine coronary artery endothelial cells (PCAECs).
Plasma-nanocoated L605 coupons contain Si–O bonding, which provided good corrosion resistance because of the lower dissolution rate of Si–O bonding compared to other metal oxides. Si–O also can be the reason for less ion releasing from plasma-nanocoated samples compared to uncoated L605. Cell attachment and proliferation were affected by changes in surface wettability. On TMS plasma nanocoating surfaces, PCAEC and PCASMC attachment was hindered due to their hydrophobic nature. This could be attributed to the presence of proteins at the interface between cells and substrates. However, if the surface becomes too hydrophilic, proteins may fail to attach, resulting in poor cell adhesion. Surface wettability is not the sole factor influencing cell growth; NO may also play a role in this phenomenon since it is known to inhibit SMC proliferation and adhesion. These N and O elements can exist in various N- and O-containing chemical groups attached to the plasma nanocoating surfaces.

Conclusions:
These results suggest that TMS plasma nanocoatings with NH3/O2 plasma post-treatment possess the desired biocompatibility for stent applications and support the hypothesis that nanocoated stents could be very effective for in-stent restenosis prevention.