A novel three dimensional blood brain barrier (BBB) platform was developed by independently supplying different types of media to separate cell types within a single device. One channel (vascular channel, VC) is connected to the inner lumen of the vascular network while the other supplies media to the neural cells (neural channel, NC). Compared to co-cultures supplied with only one type of medium (or 1:1 mixture), best barrier properties and viability were obtained with culturing HUVECs with endothelial growth medium (EGM) and neural cells with neurobasal medium supplemented with fetal bovine serum (NBMFBS) independently. The measured vascular network permeability were comparable to reported in vivo values (20 kDa FITC-dextran, 0.45 ± 0.11 × 10−6 cm/s; 70 kDa FITC-dextran, 0.36 ± 0.05 × 10−6 cm/s) and a higher degree of neurovascular interfacing (astrocytic contact with the vascular network, GFAP-CD31 stain overlap) and presence of synapses (stained with synaptophysin). The BBB platform can dependably imitate the perivascular network morphology and synaptic structures characteristic of the NVU. This microfluidic BBB model can find applications in screening pharmaceuticals that target the brain for in neurodegenerative diseases.

The brain is one of the most important and complex organs in the human body. Although various neural network models have been proposed for in vitro 3D neuronal networks, it has been difficult to mimic functional and structural complexity of the in vitro neural circuit. Here, a microfluidic model of a simplified 3D neural circuit is reported. First, the microfluidic device is filled with Matrigel and continuous flow is delivered across the device during gelation. The fluidic flow aligns the extracellular matrix (ECM) components along the flow direction. Following the alignment of ECM fibers, neurites of primary rat cortical neurons are grown into the Matrigel at the average speed of 250 μm d(-1) and form axon bundles approximately 1500 μm in length at 6 days in vitro (DIV). Additionally, neural networks are developed from presynaptic to postsynaptic neurons at 14 DIV. The establishment of aligned 3D neural circuits is confirmed with the immunostaining of PSD-95 and synaptophysin and the observation of calcium signal transmission.

Highlights d Injured axons upregulate PlGF, which activates VEGFR1 in Schwann cells d VEGFR1 activates the formation of constricting actin spheres in Schwann cells d Constricting actin spheres accelerate the disintegration of injured axons d VEGFR1 expression in oligodendrocytes accelerates injured axon disintegration

Since the advent of organ-on-a-chip, many researchers have tried to mimic the physiology of human tissue on an engineered platform. In the case of brain tissue, structural connections and cell–cell interactions are important factors for brain function. The recent development of brain-on-a-chip is an effort to mimic those structural and functional aspects of brain tissue within a miniaturized engineered platform. From this perspective, we provide an overview of trace of brain-on-a-chip development, especially in terms of complexity and high-content/high-throughput screening capabilities, and future perspectives on more in vivo-like brain-on-a-chip development.