Summary This grant application is a renewal of an NIH-funded project in developing bioresorbable metallic stents in treatment of heart disease. The goal of this study is to optimize a novel bioresorbable zinc-based drug-eluting stents for pediatric cardiovascular applications and conduct comprehensive in vitro and in vivo testing to evaluate their efficacy. Coarctation of the aorta is a common heart defect in children, causing narrowing of the aorta and resulting in various symptoms. Traditional metallic drug-eluting stents are not suitable for pediatric patients due to their interference with artery development. To address this, biodegradable drug-eluting stents (BDES) are being explored. However, current materials have limitations in mechanical strength and degradation. To overcome this, a new solution called biodegradable zinc-lithium-manganese (Zn-Li-Mn) stents with a drug-eluting coating (Z- DES) has been developed. These stents offer mechanical strength, ductility, and stable biodegradation. The study aims to optimize the composition and configuration of Z-DES and evaluate its efficacy. In Aim 1, different Zn-Li-Mn alloys coated with PLLA and Sirolimus will be tested for mechanical properties and biocompatibility. Aim 2 focuses on assessing Z-DES biodegradation and safety in rat abdominal aortas. Aim 3 aims to validate Z-DES in a large animal model with narrowed aortas. The success of this research could lead to biodegradable pediatric stents that significantly improve patient outcomes and revolutionize cardiovascular interventions in children.