Abstract

A new method to integrate poly-dl-lactide (PLA) patterned electrospun fibers with a polydimethylsiloxane (PDMS) microfluidic chip was successfully developed via lithography. Hepatocyte behavior under static and dynamic conditions was investigated. Immunohistochemical analyses indicated good hepatocyte survival under the dynamic culture system with effective hepatocyte spheroid formation in the patterned microfluidic chip vs. static culture conditions and tissue culture plate (TCP). In particular, hepatocytes seeded in this microfluidic chip under a flow rate of 10 μL/min could re-establish hepatocyte polarity to support biliary excretion and were able to maintain high levels of albumin and urea secretion over 15 days. Furthermore, the optimized system could produce sensitive and consistent responses to nano-Ag-induced hepatotoxicity during culture. Thus, this microfluidic chip device provides a new means of fabricating complex liver tissue-engineered scaffolds, and may be of considerable utility in the toxicity screening of nanoparticles.

Highlights

  • In recent years, nanotechnology has experienced dramatic developments leading to its wide application in areas such as solar energy, cosmetics, food production, and drug delivery [1]

  • Many in vivo models have been developed to evaluate the potential toxicity of nanoparticles, improved methods are needed to decrease the numbers of animals required for testing along with the experimental expenses, and to improve the accuracy, comparability, and reproducibility of experimental results

  • All the data presented are expressed as the mean ± standard deviation (SD), and analysis of variance (ANOVA) were used for statistical evaluation of the data

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Summary

Introduction

Nanotechnology has experienced dramatic developments leading to its wide application in areas such as solar energy, cosmetics, food production, and drug delivery [1]. Many in vivo models have been developed to evaluate the potential toxicity of nanoparticles, improved methods are needed to decrease the numbers of animals required for testing along with the experimental expenses, and to improve the accuracy, comparability, and reproducibility of experimental results. Previous studies have shown that many in vitro toxicity testing methods fail to identify the hazards of nanoparticles, as primary hepatocytes rapidly lose their morphology and specific functions—such as the activity of phase I and phase II enzymes and the production of plasma proteins—under traditional incubation methods [2]. Many methods have been used to create spatial variations and topologies to mediate cell aggregates; these have exhibited difficulty in mimicking the exact microenvironment of hepatocytes, combating poor oxygen and nutrient diffusion [3,4]

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