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3D Spheroids Generated on Carbon Nanotube-Functionalized Fibrous Scaffolds for Drug Metabolism and Toxicity Screening

Abstract

The mechanical and electrical stimuli have profound effect on the cellular behavior and function. In this study, a series of conductive nanofibrous scaffolds are developed by blend electrospinning of poly(styrene-co-maleic acid) (PSMA) and multiwalled-carbon nanotube (CNTs), followed by grafting galactose as cell adhesion cues. When the mass ratios of CNTs to PSMA increase up to 5%, the average diameter, alignment, Young’s modulus and conductivity of fibrous scaffolds increase, whereas the pore size and elongation at break decrease. Primary hepatocytes cultured on the scaffolds are self-assembled into 3D spheroids, which restores the hepatocyte polarity and sufficient expression of drug metabolism enzymes over an extended period of time. Among these conductive scaffolds, hepatocytes cultured on fibers containing 3% of CNTs (F3) show the highest clearance rates of model drugs, offering a better prediction of the in vivo data with a high correlation value. Moreover, the drug metabolism capability is maintained over 15 days and more sensitive to the inducers and inhibitors of metabolizing enzymes, demonstrating the applicability for drug-drug interaction studies. Thus, this culture system has demonstrated as a reliable in vitro model for high-throughput screening of metabolism and toxicity in the early phases of drug development.

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Publication details

The article was received on 19 Aug 2019, accepted on 04 Nov 2019 and first published on 05 Nov 2019


Article type: Paper
DOI: 10.1039/C9BM01310E
Biomater. Sci., 2019, Accepted Manuscript

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    3D Spheroids Generated on Carbon Nanotube-Functionalized Fibrous Scaffolds for Drug Metabolism and Toxicity Screening

    J. Wei, J. Lu, M. Chen, S. Xie, T. Wang and X. Li, Biomater. Sci., 2019, Accepted Manuscript , DOI: 10.1039/C9BM01310E

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