Patterned Fibers Embedded Microfluidic Chips Based on PLA and PDMS for Ag Nanoparticle Safety Testing

Abstract

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.

Electrospinning and microfluidics

“…Hepatocytes cultured in a controlled system under an optimized flow exhibited Micropatterned ES nanofibers [83] Biomimetic hydrogel [72] Lab-on-a-chip (LOC) devices Escherichia coli biosensor [90] Circulating tumor cells detection [96] Cancer biomarkers detection [101] restored hepatocyte polarity and biliary excretion, and maintained liver-specific functions. In these conditions, they were able to produce sensitive and consistent Ag nanoparticles toxicity responses at different time points, demonstrating the feasibility of the patterned fiber-embedded microfluidic chips as a potential in vitro screening model for toxicological studies [84]. Alternatively, the combination of 3D-hydrogel and microfluidic devices also has been reported as a means to provide in vivo-like 3D conditions [75,76].…”

“…As a further improvement, patterned electrospun fibers have been produced and successfully integrated into microfluidic devices with the aim to better mimic the topography of the natural ECM [80,83,84]. This ability to create controlled cell microenvironments through spatially defined fibrous structures becomes increasingly important for studying and/or controlling phenotype expression in tissue engineering and drug-discovery applications.…”

“…In this framework, fiber pads have been integrated with microfluidic networks to study the combined effects of surface topography and chemical gradients on neural stem cells cultured in microfluidic channels on differently aligned ES substrates [80]. The combined effect of microfluidics and patterned-electrospun fibers on hepatocyte behavior has also been studied [84]. Hepatocytes cultured in a controlled system under an optimized flow exhibited Micropatterned ES nanofibers [83] Biomimetic hydrogel [72] Lab-on-a-chip (LOC) devices Escherichia coli biosensor [90] Circulating tumor cells detection [96] Cancer biomarkers detection [101] restored hepatocyte polarity and biliary excretion, and maintained liver-specific functions.…”

The Use of Microfluidics in Cytotoxicity and Nanotoxicity Experiments

“…In order to improve the cellular seeding and viability of hepatocytes in a microchannel, the group of Liu et al [ 72 ] produced an electrospun biocompatible scaffold inside of a microfluidic device. By creating a 3D micro-environment of fibres for the liver cells, they were able to form a micro-perfusion environment which overcame the previous limitations of the lack of scaffold stiffness and the permeability to large molecules/cells.…”

Polymethacrylate Coated Electrospun PHB Fibers as a Functionalized Platform for Bio-Diagnostics: Confirmation Analysis on the Presence of Immobilized IgG Antibodies against Dengue Virus

“…Electrospun fiber mats have also proven to be suitable candidates for biosensors due to their high specific surface area, controllable porosity, interconnectivity, and low cost [ 14 , 15 ]. Electrospun fibers of different classes can be integrated into the microfluidic platforms such as lab-on-a-chip (LOC) and/or lab-on-a-compact disk (LOCD) devices for extreme point of care (EPOC) [ 16 ]. Although the physical properties of such versatile fiber mats promote biomolecular interaction, the presence of active functional groups such as carboxyl (–COOH), amine (–NH 2 ), hydroxyl (–OH), and/or sulfhydryl (–SH) in the structure of the fibers can further facilitate analyte-surface interaction in an efficient manner [ 8 , 14 , 17 ].…”