Nanometabolomics elucidated biological response of 3D printed vascular stents: Towards metabolic reprogramming of metabolome and lipidome

3D printed vascular stent (3D-PVS) fabricated based on the specific vascular structure has provided an excellent solution in therapy of cardiovascular disease (CVD). However, the 3D-PVS-based biocompatibility analysis was still remained at the phenotypic level stage while deeper molecular mechanism was urgent to be explored in order to provide theoretical and technical support for the clinical application of 3D-PVS. Fortunately, nanometabolomics proposed and applied in our latest research could offer an excellent alternative for elucidating detailed molecular mechanisms involved in “3D-PVS-organism” interaction through 3D-PVS-related untargeted/targeted aqueous metabolomics, lipidomics, and spatial metabolomics. In this work, the biological response and relevant molecular mechanism of 3D-PVS was elucidated by nanometabolomics. Thereinto, untargeted nanometabolomics was performed for primary profiling of 3D-PVS-induced alteration in cell metabolism, then targeted nanometabolomics was carried out in rat model for in-depth investigation of 3D-PVS-induced metabolic reprogramming based on above untargeted nanometabolomics results. The untargeted nanometabolomics results revealed that the in vitro safe range of concentration (including low concentration (5 mg/mL) and high concentration (15 mg/mL)) of 3D-PVS could lead to strong disturbance of amino acids or organic acids-related metabolism and phospholipids, sphingolipids or glycerolipids-related metabolism. In addition, targeted nanometabolomics results further elucidated the in vivo 3D-PVS-induced promotion in glycolysis and amino acid metabolism and homeostasis of some lipid classes. This work could be consider as a far-reaching exploration on 3D-PVS at a phenotypic and molecular level, which also shed light on its further biomedical application based on nanometabolomics bioinformation. © 2025 Elsevier B.V.