Evaluation of nickel release from Ni-Ti stents in various media for safety assessment purposes

Nickel (Ni) was an essential component of Ni-Ti alloys used in cardiovascular implants. However, the release of Ni from these alloys might pose potential health risks. This study aimed to identify a simple extraction medium for evaluating Ni release from Ni-Ti alloys and to establish safety assessment guidelines. Seven extraction media, including 0.005% HCl and goat whole blood, were tested. The Ni release was analyzed using inductively coupled plasma atomic emission spectroscopy (ICP-AES) and statistical methods. The results indicated that 0.005% HCl could replace goat blood, as it showed comparable Ni release levels and provided a more conservative assessment. The optimal extraction medium was validated over 41 days at 37 °C. The Ni release curves demonstrated higher release in 0.005% HCl than in physiological media. Safety evaluation against the International Council for Harmonisation's (ICH) permissible daily exposure (PDE) of 20 μg/day revealed that some samples exceeded the limits, highlighting the need for stringent risk assessment. This study provided a practical method for Ni release evaluation, supporting regulatory oversight and enhancing product safety in the medical device industry.