The biological effects of copper alloying in Zn-based biodegradable arterial implants

Abstract

Biodegradable metals based on zinc are being developed to serve as temporary arterial scaffolding. Although the inclusion of copper is becoming more prevalent for grain refinement in zinc alloys, the biological activity of the copper component has not been well investigated. Here, two ZnCu alloys (0.8 and 1.5 wt% Cu) with and without thermal treatment were investigated for their hemocompatibility and biocompatibility. The microstructure was examined using scanning electron microscopy and X-ray diffraction. Zn-1.5Cu was found to contain nearly double the amount of second phase (CuZn5) precipitates as compared to Zn-0.8Cu. Thermal treatment dissolved a portion of the precipitates into the matrix. Since copper is a well-known catalyst for NO generation, the metals were tested both for their ability to generate NO release and for their thrombogenicity. Cellular responses and in vivo corrosion were characterized by a 6 months in vivo implantation of metal wires into rat arteries. The as-received Zn-1.5Cu displayed the least neointimal growth and smooth muscle cell presence, although inflammation was slightly increased. Thermal treatment was found to worsen the biological response, as determined by an increased neointimal size, increased smooth muscle cell presence and small regions of necrotic tissue. There were no trends in NO release between the alloys and thermal treatments. Corrosion progressed predominately through a pitting mechanism in vivo, which was more pronounced for the thermally treated alloys, with a more uniform corrosion seen for as-drawn Zn-1.5Cu. Differences in biological response are speculated to be due to changes in microstructure and pitting corrosion behavior.