BiocompatibilityBiocompatibility studies for arterial stents have historically relied on young, healthy animal models, yet most human patients requiring these devices are older and suffer from atherosclerosis. This mismatch may lead to inaccurate predictions about the performance of conventional and bioresorbable metals. Two recent studies highlight the divergent biological responses to arterial implants in aged and diseased animal models. In one, biodegradable zincZinc and inert platinum wires were implanted in young and old rats, revealing ageAge-related reductionsReduction in inflammation and smooth muscle cell activity, with paradoxically larger neointimal growth in older animals receiving zincZinc implants. In another, platinum wires implanted in hypercholesterolemic ApoE−/− mice led to dramatic increases in inflammation, lipid deposition, and neointimal size compared to healthy counterparts. Together, these studies underscore the critical importance of incorporating both ageAge and diseaseDisease state into preclinical testing. The over-reliance on young, healthy models may overestimate the compatibility of some materials while underestimating risks in atherosclerotic arteries. A paradigm shift towards including more realistic models is essential to accurately evaluate and optimize next-generation stent materials.