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Barrier functionality of the blood-brain barrier (BBB) is provided by the tight junctions formed by a monolayer of the human brain endothelial cells (HBECs) internally around the blood capillaries. To mimic such barrier functionality in vitro, replicating the hollow tubular structure of the BBB along with the HBECs monolayer on its inner surface is crucial. Here, we developed an invasive microfluidic technique to obtain the HBECs monolayer on the inner surface of alginate-based hollow microfibers. The HBECs were seeded on the inner surface of these microfibers using a custom-built microfluidic device. The seeded HBECs were monitored for 9 days after manufacturing and cultured to form a monolayer on the inner surface of the alginate hollow microfibers in the maintenance media. A higher cell seeding density of 217 cells/mm length of the hollow microfiber was obtained using our microfluidic technique. Moreover, high accuracy of around 96 % was obtained in seeding cells on the inner surface of alginate hollow microfibers. The microfluidic method illustrated in this study could be extrapolated to obtain a monolayer of different cell types on the inner surface of alginate hollow microfibers with cell-compatible ECM matrix proteins. Furthermore, it will enable us to mimic a range of microvascular systems in vitro by closely replicating the structural attributes of the native structure.

At present, the blood-brain barrier (BBB) poses a challenge for treating a wide range of central nervous system disorders; reliable BBB models are still needed to understand and manipulate the transfer of molecules into the brain, thereby improving the efficiency of treatments. In this study, hollow, cell-laden microfibers are fabricated and investigated as a starting point for generating BBB models. The genetic effects of the manufacturing process are analyzed to understand the implications of encapsulating cells in this manner. These fibers are created using different manufacturing parameters to understand the effects on wall thickness and overall diameter. Then, dopaminergic rat cells are encapsulated into hollow fibers, which maintained at least 60% live cells throughout the three-day observation period. Lastly, genetic changes tyrosine hydroxylase (TH) and tubulin beta 3 class III (TUBB-3) are investigated to elucidate the effects on cell health and behavior; while the TH levels in encapsulated cells were similar to control cells, showing similar levels of TH synthesis, TUBB-3 was downregulated, indicating lower amounts of cellular neurogenesis.

The manufacturing of 3D cell scaffoldings provides advantages for modeling diseases and injuries by physiologically relevant platforms. A triple-flow microfluidic device was developed to rapidly fabricate alginate/graphene hollow microfibers based on the gelation of alginate induced with CaCl2. This five-channel pattern actualized continuous mild fabrication of hollow fibers under an optimized flowing rate ratio of 300: 200: 100 μL.min−1. The polymer solution was 2.5% alginate in 0.1% graphene, and a 30% polyethylene glycol solution was used as the sheath and core solutions. The morphology and physical properties of microstructures were investigated by scanning electron microscopy, electrochemical, and surface area analyzers. Subsequently, these conductive microfibers’ biocompatibility was studied by encapsulating mouse astrocyte cells within these scaffolds. The cells could successfully survive both the manufacturing process and prolonged encapsulation for up to 8 days. These unique 3D hollow scaffolds could significantly enhance the available surface area for nutrient transport to the cells. In addition, these conductive hollow scaffolds illustrated unique advantages such as 0.728 cm3.gr−1 porosity and twice more electrical conductivity in comparison to alginate scaffolds. The results confirm the potential of these scaffolds as a microenvironment that supports cell growth.

Mimicking microvascular tissue microenvironment in vitro calls for a cytocompatible technique of manufacturing biocompatible hollow microfibers suitable for cell-encapsulation/seeding in and around them. The techniques reported to date either have a limit on the microfiber dimensions or undergo a complex manufacturing process. Here, a microfluidic-based method for cell seeding inside alginate hollow microfibers is designed whereby mouse astrocytes (C8-D1A) are passively seeded on the inner surface of these hollow microfibers. Collagen I and poly-d-lysine, as cell attachment additives, are tested to assess cell adhesion and viability; the results are compared with nonadditive-based hollow microfibers (BARE). The BARE furnishes better cell attachment and higher cell viability immediately after manufacturing, and an increasing trend in the cell viability is observed between Day 0 and Day 2. Swelling analysis using percentage initial weight and width is performed on BARE microfibers furnishing a maximum of 124.1% and 106.1%, respectively. Degradation analysis using weight observed a 62% loss after 3 days, with 46% occurring in the first 12 h. In the frequency sweep test performed, the storage modulus (G') remains comparatively higher than the loss modulus (G″) in the frequency range 0-20 Hz, indicating high elastic behavior of the hollow microfibers.

Carbon-modified fibrous structures with high biocompatibility have attracted much attention as supercapacitors due to their low cost, sustainability, abundance, and excellent electrochemical performance. However, some of these carbon-based materials suffer from low specific capacitance and electrochemical performance, which have been significant challenges in developing biocompatible electronic devices. In this regard, several studies have been reported on the development of 3D carbon-based micro architectures that provided high conductivity, energy storage potential, and 3D porosity frameworks. This study reports manufacturing of microfluidic Alginate hollow microfiber modified by water-soluble modified Graphene (BSA-Graphene). These architectures successfully exhibited conductivity enhancement conductivity of about 20 times more compared to Alginate hollow microfibers, and without any significant change in the inner-dimension values of hollow region (220.0 ± 10.0 µm) in comparison with pure alginate hollow microfibers. In the presence of Graphene, more obtained specific surface permeability and active ion adsorption sites could successfully provide as shorter pathways. These obtained continuous ion transport networks resulted in improved electrochemical performance. These desired electrochemical properties of the microfibers make Alginate/Graphene hollow fibers an excellent choice for further use in the development of lightweight flexible supercapacitors with scalable potential to be used in intelligent health electronic gadgets.

Engineering conductive 3D cell scaffoldings offer advantages toward the creation of physiologically relevant platforms with integrated real-time sensing capabilities. Dopaminergic neural cells are encapsulated into graphene-laden alginate microfibers using a microfluidic approach, which is unmatched for creating highly-tunable microfibers. Incorporating graphene increases the conductivity of the alginate microfibers by 148%, creating a similar conductivity to native brain tissue. The cell encapsulation procedure has an efficiency of 50%, and of those cells, ≈30% remain for the entire 6-day observation period. To understand how the microfluidic encapsulation affects cell genetics, tyrosine hydroxylase, tubulin beta 3 class 3, interleukin 1 beta, and tumor necrosis factor alfa are analyzed primarily with real-time reverse transcription-quantitative polymerase chain reaction and secondarily with enzyme-linked immunosorbent assay, immediately after manufacturing, after encapsulation in polymer matrix for 6 days, and after encapsulation in the graphene-polymer composite for 6 days. Preliminary data shows that the manufacturing process and combination with alginate matrix affect the expression of the studied genes immediately after manufacturing. In addition, the introduction of graphene further changes gene expressions. Long-term encapsulation of neural cells in alginate and 6-day exposure to graphene also leads to changes in gene expressions.

The microvasculature is a vital organ that distributes nutrients within tissues, and collects waste products from them, and which defines the environmental conditions in both normal and disease situations. Here, a microfluidic chip was developed for the fabrication of poly(ethylene glycol diacrylate) (PEGDA)-based hollow self-standing microvessels having inner dimensions ranging from 15 μm to 73 μm and displaying biocompatibility/cytocompatibility. Macromer solutions were hydrodynamically focused into a single microchannel to form a concentric flow regime, and were subsequently solidified through photopolymerization. This approach uniquely allowed the fabrication of hollow microvessels having a defined structure and integrity suitable for cell culturing.

Growth in open-source hardware designs combined with the decreasing cost of high-quality 3D printers have supported a resurgence of in-house custom lab equipment development. Herein, we describe a low-cost (< $400), open-source CO2incubator. The system is comprised of a Raspberry Pi computer connected to a 3D printer controller board that has controls for a CO2sensor, solenoid valve, heater, and thermistors. CO2is supplied through the sublimation of dry ice stored inside a thermos to create a sustained 5% CO2supply. The unit is controlled via G-Code commands sent by the Raspberry Pi to the controller board. In addition, we built a custom software application for remote control and used the open-source Grafana dashboard for remote monitoring. Our data show that we can maintain consistent CO2and temperature levels for over three days without manual interruption. The results from our culture plates and real-time PCR indicate that our incubator performed equally well when compared to a much more expensive commercial CO2incubator. We have also demonstrated that the antibiotic susceptibility assay can be performed in this low-cost CO2incubator. Our work also indicates that the system can be connected to incubator chambers of various chamber volumes.

In article number 1800112, Nicole N. Hashemi and co‐workers report a placenta‐on‐a‐chip device, an in vitro microfluidic cell culture platform, that is utilized to investigate the exchange of substances across the placenta. Caffeine, a xenobiotic substance, is one of the most widely consumed stimulants in the world. The device is used to perform a quantitative analysis of caffeine transport across the placental barrier.

Due to the particular structure and functionality of the placenta, most current human placenta drug testing methods are limited to animal models, conventional cell testing, and cohort/controlled testing. Previous studies have produced inconsistent results due to physiological differences between humans and animals and limited availability of human and/or animal models for controlled testing. To overcome these challenges, a placenta‐on‐a‐chip system is developed for studying the exchange of substances to and from the placenta. Caffeine transport across the placental barrier is studied because caffeine is a xenobiotic widely consumed on a daily basis. Since a fetus does not carry the enzymes that inactivate caffeine, when it crosses a placental barrier, high caffeine intake may harm the fetus, so it is important to quantify the rate of caffeine transport across the placenta. In this study, a caffeine concentration of 0.25 mg mL−1 is introduced into the maternal channel, and the resulting changes are observed over a span of 7.5 h. A steady caffeine concentration of 0.1513 mg mL−1 is reached on the maternal side after 6.5 h, and a 0.0033 mg mL−1 concentration on the fetal side is achieved after 5 h.