Plasma nanocoatings on cobalt chromium L605 alloy for cardiovascular stent applications
Authors:   , Phan ThiThuHa 
Published: February 2023

[EMBARGOED UNTIL 8/1/2023] Coronary stents have been essential devices in treating blocked coronary arteries, Unfortunately, they face in-stent restenosis and thrombosis complications. Drug eluting stents (DES) have been developed to minimize restenosis, but could cause late-thrombosis and poor endothelialization. Furthermore, DES require dual-antiplatelet therapy (DAPT) to prevent thrombosis. DAPT usage is problematic for patients with high bleeding risk, and minimal DAPT duration less than one month is desired. Bioactive stent coatings, which do not elute drugs, may be an alternative to DES. In this study, cobalt chromium (CoCr) L605 coronary artery stents and coupons were coated with Trimethysilane (TMS) plasma nanocoatings of 20-25 nm in thickness. Direct current (DC) glow discharges were utilized for TMS plasma coatings and additional NH3/O2 plasma surface modification. Effects of plasma nanocoatings on CoCr L605 alloy surfaces were studied in terms of: 1) Surface properties, 2) In vitro biological responses, and 3) corrosion behavior. The plasma nanocoating surfaces were characterized by contact angle measurement, Fourier-transform infrared spectroscopy (FTIR), X-ray photoelectron spectroscopy (XPS), and scanning electron microscope (SEM). Mechanical stability of the plasma nanocoating was evaluated using a tape adhesion test (coupon) and SEM (stent). Chemical stability of the plasma nanocoatings were studied by contact angle measurements, FTIR, and XPS spectroscopy up to 2 years. A series of in vitro experiments were conducted to find out the effect of plasma nanocoatings in improving cell proliferation selectively toward endothelial cells (ECs), while inhibiting smooth muscle cells (SMCs) proliferation and platelet adhesion and activation. These in vitro experiments include cell culture, cell migration, cell co-culture, protein adsorption, platelet adhesion and activation under static and flow conditions. Corrosion behavior of plasma nanocoatings was assessed by immersion test, electrochemical tests, ion releasing, and cytotoxicity test. Results show that NH3/O2 modified TMS plasma nanocoating is hydrophilic. Though aging occurs gradually, NH3/O2 modified plasma nanocoating surface is more hydrophilic (48.5 degrees after 2-year aging) than the uncoated counterpart. NH3/O2 modified TMS plasma coatings mostly contain O-, Si- and C- rich functionalities (39.39 at. percent, 31.92 at. percent, and 24.12 at. percent, respectively) and a very small but essential amount of N (2.77 at. percent). Modified plasma nanocoatings contain nitric oxide (NO)-like functionalities which play an essential role in their biological responses. Plasma nanocoatings with NH3/O2 plasma modification maintained similar level of porcine coronary artery endothelial cell (PCAEC) proliferation while porcine coronary artery smooth muscle cell (PCASMC) viability decreased by 73 percent after 7-day incubation compared to those on uncoated bare L605 surfaces. PCAEC and PCASMC cell co-culture and migration were also conducted. In cell co-culture, the cell ratio of PCAEC/PCASMC on NH3/O2 modified TMS plasma nanocoatings was 1.5-fold higher than that of uncoated bare L605. Migration test showed comparable PCAEC migration distance for uncoated L605 and NH3/O2 modified TMS plasma nanocoatings. In contrast, PCASMC migration distance reduced 6-fold for TMS plasma nanocoatings without the NH3/O2 plasma modification. Lower adhered platelets distribution (70 percent decrease) and less platelet activation were observed on NH3/O2 modified TMS plasma nanocoated surfaces compared to uncoated L605. Corrosion resistance was improved with TMS plasma nanocoatings by decreasing corrosion rates and increasing corrosion potential, no pitting corrosion, and no mineral adsorption layer. Ion releasing test by inductively coupled plasma mass spectrometry (ICP-MS) revealed that Co, Cr, Ni ion concentrations reduced 57-72 percent for plasma nanocoatings compared to uncoated L605. TMS plasma nanocoatings showed no sign of cytotoxicity. In vitro tests provide strong evidence that TMS plasma nanocoatings with NH3/O2 plasma surface modification may be a promising approach for preventing both restenosis and thrombosis in stent applications.