Nanoplastics (NPs) released during the aging of green energy infrastructure may pose significant threats to human vascular health. Here, we developed a three-dimensional (3D) bioprinted blood vessel organoid (BVO) platform using hiPSC-derived arterial endothelial cells and smooth muscle cells to assess the toxicity of 40 nm and 100 nm polystyrene NPs. Our results demonstrate that 100 nm NPs exhibit more severe vasculotoxicity than 40 nm particles. In 2D assays, 100 nm NPs significantly impaired angiogenic capacity, reducing endothelial nodes from 1329.7±132.7 to 373.7±62.5 and junctions from 381.0±35.2 to 105.0±18.2 (p < 0.001). In 3D BVOs, NP exposure led to an 80%-90% reduction in vessel junctions and total network length. Single-cell transcriptomics revealed a profound remodeling of the cellular landscape. Specifically, the angiogenic endothelial subpopulation was entirely depleted in the 100 nm NP group. Concurrently, activated fibroblasts and mesenchymal stromal cells (MSC2) expanded, indicating an endothelial-to-mesenchymal transition (EndMT)-like shift. Transcriptomic profiling further confirmed the dysregulation of mechanotransduction and pro-survival signaling. This study establishes a human relevant platform for evaluating NPs' toxicity. These findings provide a mechanistic foundation for understanding how plastic debris destabilizes vascular homeostasis, offering a sustainable solution for environmental health monitoring. • 3D bioprinted BVOs evaluate size-dependent NPs vasculotoxicity. • 100 nm NPs reduce endothelial nodes to 373.7 with 90% junction loss. • NPs exposure impairs 3D vascular network assembly and cell viability. • ScRNA-seq reveals complete depletion of angiogenic endothelial populations. • EndMT-like shifts and signaling dysregulation are identified via scRNA-seq.
Zhang et al. (Sun,) studied this question.