Microfluidic Chip-Based Modeling of Three-Dimensional Intestine–Vessel–Liver Interactions in Fluorotelomer Alcohol Biotransformation

作者：Ning Xu, Haifeng Lin, Jin‐Ming Lin, Jie Cheng, Peilong Wang, Ling Lin · 发表于：Analytical Chemistry · 年份：2023 · DOI：10.1021/acs.analchem.3c03892 · 被引用次数：14 · 研究领域：Per- and polyfluoroalkyl substances research

Plyfluoroalkyl substance (PFAS), featured with incredible persistence and chronic toxicity, poses an emerging ecological and environmental crisis. Although significant progress has been made in PFAS metabolism in vivo, the underlying mechanism of metabolically active organ interactions in PFAS bioaccumulation remains largely unknown. We developed a microfluidic-based assay to recreate the intestine-vessel-liver interface in three dimensions, allowing for high-resolution, real-time images and precise quantification of intestine-vessel-liver interactions in PFAS biotransformation. In contrast to the scattered arrangement of vascular endothelium on the traditional d-polylysine-modified two-dimensional (2D) plate, the microtubules in our three-dimensional (3D) platform formed a dense honeycomb network through the ECM, with longer tubular structures. Additionally, the slope culture of epithelial cells in our platform exhibited a closely arranged and thicker cell layer than the planar culture. To dynamically monitor the metabolic crosstalk in the intestinal-vascular endothelium-liver interaction under exposure to fluorotelomer alcohols (FTOHs), we combined the chip with a solid-phase extraction-mass spectrometry (SPE-MS) system. Our findings revealed that endothelial cells were involved in the metabolic process of FTOHs. The transformation of intestinal epithelial and hepatic epithelial cells produces toxic metabolite fluorotelomer carboxylic acids (FTCAs), which circulate to endot...