3D printed biomimetic blade stirrer for expedient estimation of the oral bioavailability of contaminants of emerging concern.

A 3D printed biomimetic blade-based microextraction device with covalently attached phosphatidylcholine (PC) is proposed as a proof-of-concept platform for the in vitro estimation of the oral bioavailability of plastic-borne organic substances with distinct physicochemical properties. The experimental conditions were designed to resemble the murine small-intestinal brush-border membrane by approximating its PC mass-to-volume ratio. The biomimetic extraction efficiency (E, %), defined as the percentage of the analyte partitioned into the PC-functionalized 3D-printed surface, was investigated as a potential in vitro descriptor. By building a multiple linear regression model incorporating E along with the solubility, hydrogen acceptor, topological polar surface area, and the aromaticity (AR) of the target compounds, an internal leave-one-out cross-validation root mean squared error (RMSE) of 7.3%, a mean absolute error of 6.2%, a bias of 1.1 and a cross validated coefficient of determination of 0.941 were obtained. As a result, the prediction error relative to the reference baseline mean prediction model is reduced by ~ 79%. The statistically significant contribution of E as an interaction term (E: AR, p < 0.01) along with the decrease of RMSE by 30% as compared to models without incorporating E suggest that the experimentally derived biomimetic descriptor captures membrane-analyte interactions that are not fully encoded by conventional physicochemical parameters. The modular design of the platform based on exchangeable blades, the low fabrication cost, and the compatibility with standard laboratory equipment supports our 3D printed biomimetic tool as a potential scalable screening tool for in vitro bioavailability assessment without need of animal models.