Restorative supramolecular polymers for vascular Grafts: An integrated ADMET evaluation

• Supramolecular polyurethane vascular grafts emerge as a safe and promising option. • The ADMET framework is applied using available bench, preclinical and clinical data. • The supramolecular implants undergo local absorption followed by renal clearance. • It was demonstrated that oxidation mechanisms previousy described for biostable polyurethanes can be applied successfully to describe oxidation of supramolecular biodegradable implants with limited modifications. Supramolecular polyurethanes incorporating ureidopyrimidinone (UPy) motifs are emerging as transformative materials for restorative vascular grafts. This study presents an integrated ADMET (Absorption, Distribution, Metabolism, Excretion, Toxicology) evaluation of a supramolecular polyurethane vascular graft, combining bench, preclinical, and clinical data. The graft leverages advances in supramolecular chemistry to achieve controlled degradation profiles, supporting endogenous tissue restoration and safe excretion of degradation products. Bench and animal studies demonstrate that oxidative pathways, mediated by macrophages and foreign body giant cells, dominate the absorption and metabolism of these materials, which remain localized at the implant site. Ongoing clinical trials support adequate safety profiles and favorable patency rates compared to conventional grafts, while toxicological assessments confirm that the aliphatic UPy-polyurethane does not generate harmful byproducts and meets ISO standards for local and systemic safety. Collectively, these findings support the clinical translation of supramolecular polyurethanes as advanced restorative materials for vascular applications, offering a robust safety and efficacy profile.