The advent of 3D printing technologies promises to make microfluidic organ-on-chip technologies more accessible for the biological research community. To date, hydrogel-encapsulated cells have been successfully incorporated into 3D printed microfluidic devices. However, there is currently no 3D printed microfluidic device that can support multicellular spheroid culture, which facilitates extensive cell–cell contacts important for recapitulating many multicellular functional biological structures. Here, we report a first instance of fabricating a 3D printed microfluidic cell culture device capable of directly immobilizing and maintaining the viability and functionality of 3D multicellular spheroids. We evaluated the feasibility of two common 3D printing technologies i.e. stereolithography (SLA) and PolyJet printing, and found that SLA could prototype a device comprising of cell immobilizing micro-structures that were housed within a microfluidic network with higher fidelity. We have also implemented a pump-free perfusion system, relying on gravity-driven flow to perform medium perfusion in order to reduce the complexity and footprint of the device setup, thereby improving its adaptability into a standard biological laboratory. Finally, we demonstrated the biological performance of the 3D printed device by performing pump-free perfusion cultures of patient-derived parental and metastatic oral squamous cell carcinoma tumor and liver cell (HepG2) spheroids with good cell viability and functionality. This paper presents a proof-of-concept in simplifying and integrating the prototyping and operation of a microfluidic spheroid culture device, which will facilitate its applications in various drug efficacy, metabolism and toxicity studies.

The practical application of microfluidic liver models for in vitro drug testing is partly hampered by their reliance on human primary hepatocytes, which are limited in number and have batch-to-batch variation. Human stem cell-derived hepatocytes offer an attractive alternative cell source, although their 3D differentiation and maturation in a microfluidic platform have not yet been demonstrated. We develop a pump-free microfluidic 3D perfusion platform to achieve long-term and efficient differentiation of human liver progenitor cells into hepatocyte-like cells (HLCs). The device contains a micropillar array to immobilize cells three-dimensionally in a central cell culture compartment flanked by two side perfusion channels. Constant pump-free medium perfusion is accomplished by controlling the differential heights of horizontally orientated inlet and outlet media reservoirs. Computational fluid dynamic simulation is used to estimate the hydrostatic pressure heads required to achieve different perfusion flow rates, which are experimentally validated by micro-particle image velocimetry, as well as viability and functional assessments in a primary rat hepatocyte model. We perform on-chip differentiation of HepaRG, a human bipotent progenitor cell, and discover that 3D microperfusion greatly enhances the hepatocyte differentiation efficiency over static 2D and 3D cultures. However, HepaRG progenitor cells are highly sensitive to the time-point at which microperfusion is applied. Isolated HepaRG cells that are primed as static 3D spheroids before being subjected to microperfusion yield a significantly higher proportion of HLCs (92%) than direct microperfusion of isolated HepaRG cells (62%). This platform potentially offers a simple and efficient means to develop highly functional microfluidic liver models incorporating human stem cell-derived HLCs. Biotechnol. Bioeng. 2017;114: 2360-2370. © 2017 Wiley Periodicals, Inc.

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In the present work, numerical simulations were conducted for a typical end-to-side distal graft anastomosis to assess the effects of inducing secondary flow, which is believed to remove unfavourable flow environment. Simulations were carried out for four models, generated based on two main features of 'out-of-plane helicity' and 'spiral ridge' in the grafts as well as their combination. Following a qualitative comparison against in vitro data, various mean flow and hemodynamic parameters were compared and the results showed that helicity is significantly more effective in inducing swirling flow in comparison to a spiral ridge, while their combination could be even more effective. In addition, the induced swirling flow was generally found to be increasing the wall shear stress and reducing the flow stagnation and particle residence time within the anastomotic region and the host artery, which may be beneficial to the graft longevity and patency rates. Finally, a parametric study on the spiral ridge geometrical features was conducted, which showed that the ridge height and the number of spiral ridges have significant effects on inducing swirling flow, and revealed the potential of improving the efficiency of such designs.

Dry epidermal electrodes that can always form conformal contact with skin can be used for continuous long-term biopotential monitoring, which can provide vital information for disease diagnosis and rehabilitation. But, this application has been limited by the poor contact of dry electrodes on wet skin. Herein, we report a biocompatible fully organic dry electrode that can form conformal contact with both dry and wet skin even during physical movement. The dry electrodes are prepared by drop casting an aqueous solution consisting of poly­(3,4-ethylenedioxythiophene):polystyrenesulfonate (PEDOT:PSS), poly­(vinyl alcohol) (PVA), tannic acid (TA), and ethylene glycol (EG). The electrodes can exhibit a conductivity of 122 S cm–1 and a mechanical stretchability of 54%. Moreover, they are self-adhesive to not only dry skin but also wet skin. As a result, they can exhibit a lower contact impedance to skin than commercial Ag/AgCl gel electrodes on both dry and sweat skins. They can be used as dry epidermal electrodes to accurately detect biopotential signals including electrocardiogram (ECG) and electromyogram (EMG) on both dry and wet skins for the users at rest or during physical movement. This is the first time to demonstrate dry epidermal electrodes self-adhesive to wet skin for accurate biopotential detection.