Combinatorial biophysical cue sensor array for controlling neural stem cell fate.

Biophysical cues, such as electrical stimulus, mechanical feature, and surface topography, enable the control of neural stem cell (NSC) differentiation and neurite outgrowth. However, the effect of these biophysical cues on NSC behavior has not been fully elucidated. In the present study, we developed an innovative combinatorial biophysical cue sensor array combining a surface modified nanopillar array with conductive hydrogel micropatterns. The micro/nanopattern comprised silicon oxide-coated polyurethane nanopillar arrays on a flexible film and conductive hydrogel micropatterns including polyethylene glycol (PEG) hydrogel, silver nanowires (AgNW), and reduced graphene oxide (rGO). A computational fluid dynamic (CFD) model was used to optimize the design parameters of the nanopillar arrays. In the study, we successfully demonstrated that SiO2-coated nanopillar array enhanced the differentiation of NSCs and efficiently regulated neuronal behavior, such as neurite outgrowths, by conductive hydrogel micropatterns combined with electrical stimuli. Therefore, our innovative combinatorial biophysical cue sensor array to control NSC behavior via electrical stimuli can be potentially useful to study neurodegenerative and neurological disorder therapy applications.

rGO nanomaterial-mediated cancer targeting and photothermal therapy in a microfluidic co-culture platform.

We developed the microfluidic co-culture platform to study photothermal therapy applications. We conjugated folic acid (FA) to target breast cancer cells using reduced graphene oxide (rGO)-based functional nanomaterials. To characterize the structure of rGO-based nanomaterials, we analyzed the molecular spectrum using UV-visible and Fourier-transform infrared spectroscopy (FT-IR). We demonstrated the effect of rGO-FA-based nanomaterials on photothermal therapy of breast cancer cells in the microfluidic co-culture platform. From the microfluidic co-culture platform with breast cancer cells and human umbilical vein endothelial cells (HUVECs), we observed that the viability of breast cancer cells treated with rGO-FA-based functional nanomaterials was significantly decreased after near-infrared (NIR) laser irradiation. Therefore, this microfluidic co-culture platform could be a potentially powerful tool for studying cancer cell targeting and photothermal therapy.

Generation of tumor spheroids using a droplet-based microfluidic device for photothermal therapy.

Despite their simplicity, monolayer cell cultures are not able to accurately predict drug behavior in vivo due to their inability to accurately mimic cell-cell and cell-matrix interactions. In contrast, cell spheroids are able to reproduce these interactions and thus would be a viable tool for testing drug behavior. However, the generation of homogenous and reproducible cell spheroids on a large scale is a labor intensive and slow process compared to monolayer cell cultures. Here, we present a droplet-based microfluidic device for the automated, large-scale generation of homogenous cell spheroids in a uniform manner. Using the microfluidic system, the size of the spheroids can be tuned to between 100 and 130 µm with generation frequencies of 70 Hz. We demonstrated the photothermal therapy (PTT) application of brain tumor spheroids generated by the microfluidic device using a reduced graphene oxide-branched polyethyleneimine-polyethylene glycol (rGO-BPEI-PEG) nanocomposite as the PTT agent. Furthermore, we generated uniformly sized neural stem cell (NSC)-derived neurospheres in the droplet-based microfluidic device. We also confirmed that the neurites were regulated by neurotoxins. Therefore, this droplet-based microfluidic device could be a powerful tool for photothermal therapy and drug screening applications.