Stable Titania Nanostructures on Stainless Steel Coronary Stent Surface for Enhanced Corrosion Resistance and Endothelialization

Abstract

Stainless steel (SS) coronary stents continue to present risk of in-stent restenosis that impact its long term safety and efficacy. The present work focuses on developing a drug-free and polymer-less surface on coronary stents by utilizing a titania (TiO ) nanotexturing approach through hydrothermal processing, that will offer improved stent performance in vivo. Mechanically stable and durable nanotextured coatings are obtained on SS stents that also offer good corrosion resistance. In vitro vascular cell (endothelial and smooth muscle cells) studies on surface modified SS show preferential rapid endothelialization with enhanced nitric oxide production and reduce smooth muscle cell proliferation, in comparison to unmodified SS. In vivo evaluation of the nanotextured stents after subcutaneous implantation in rabbits show reduced irritability and minimal localized inflammatory response. These beneficial effects suggest that the stable, easily scalable titania nanosurface modification strategy on coronary stent surfaces can be a much cheaper alternative to drug eluting stents in addressing in-stent restenosis.

Successful Reduction of Neointimal Hyperplasia on Stainless Steel Coronary Stents by Titania Nanotexturing

“…In the present study, titania nanotexturing was obtained on commercial bare metal SS stents after sputter depositing TiO 2 and its subsequent hydrothermal treatment as reported earlier. 15 A distinctive uniform titania nanotopography [called hereafter as titania nanoleaf (TNL)] was generated on the abluminal and luminal surfaces of the SS stent (SS TNL), as can be noted from the scanning electron microscopy (SEM) images at different magnifications [ Figures 1 A(i–iv) and S1 ]. Individual nanoleaves having average dimensions of 115 ± 20 nm (thickness) and 650 ± 30 nm (length) were seen in the atomic force microscopy (AFM) images as well ( Figure 1 B).…”

“…These stents (TITAN) showed a significant reduction in neointimal hyperplasia in comparison to bare SS in porcine model 8 and in clinical trials. 9 − 11 Additionally, topographical modifications at the nanoscale, 12 − 14 including studies from our own group, have demonstrated the success of surface-modified SS 15 and titanium (Ti) 16 , 17 substrates in promoting endothelial cell proliferation. Research has shown that titanium surfaces having submicron patterns with lateral dimensions >100 nm could efficiently promote endothelial cell adhesion, 18 whereas titanium dioxide (TiO 2 ) nanostructures displayed a concomitant reduction in smooth muscle cell (SMC) proliferation with good endothelialization in vitro.…”

“…This material displayed improved mechanical properties and corrosion resistance, with minimal metal-ion leaching from the surface. 15 An interesting observation was the preferential adhesion and proliferation of ECs over SMCs in vitro. 15 Herein, we extend this evaluation in vivo to prove that nanotexturing of BMSs without the use of any polymers or drugs helps to evade the problem of in-stent restenosis which is routinely observed in BMSs.…”

“… 15 An interesting observation was the preferential adhesion and proliferation of ECs over SMCs in vitro. 15 Herein, we extend this evaluation in vivo to prove that nanotexturing of BMSs without the use of any polymers or drugs helps to evade the problem of in-stent restenosis which is routinely observed in BMSs. How effective is the nanotextured titania layer on SS stents in promoting endothelialization is investigated after implantation of the stents in a rabbit iliac artery for 8 weeks, in comparison to BMSs.…”

Surface Engineering of Cardiovascular Devices for Improved Hemocompatibility and Rapid Endothelialization

“…The TiO 2 nanotextured surface can improve corrosion resistance, accelerate endothelialization with enhanced NO production, and reduce smooth muscle cell (SMC) proliferation. [24] Mg-based alloys (Mg-alloys) are often used to develop biodegradable stents. The major limitations of Mg-alloys are fast degradation rate and insufficient drug loading through direct adsorption.…”