The influence of age on the biological response to biodegradable zinc arterial implants

Medical devices to treat arterial diseases of older humans are routinely designed and developed using young animals. This is the case despite the significant declines of tissue regeneration, cell proliferation, and inflammation in aged humans that are not reflected in young animals. The widespread use of age-mismatched animals is particularly a concern for the testing of interactive materials, such as biodegradable metals whose dynamic interfaces continuously impact local cell and tissue regenerative processes. In order to determine the importance and impact of age differences in biodegradable stent material biocompatibility, we implanted both inert (platinum) and biodegradable (zinc) metal wires into the arteries of 1 year old and 3-month-old rats for a period of 6 months and compared the biological responses. It was found that the older animals developed a significantly larger neointimal encapsulating tissue for zinc implants vs. a smaller tissue response for the platinum implants relative to the younger rats. The neointimas of older rats contained dramatically fewer macrophages for both implant metals. The presence of neointimal smooth muscle cells was also decreased in the older rats. Endothelial cell regeneration in the old arteries was not impacted by the different metal implants. These findings demonstrate that neointimal responses to metal implants in arterial tissue are strongly impacted by age-related changes. The findings also suggest that the reliance on young animal models to evaluate metal implants intended for the arteries of considerably older individuals may substantially over predict the biocompatibility.