Abstract
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.
Highlights
The proposed platform employs a system of two separate media microchannels to independently emulate highly localized internal and external vascular microenvironments
While typical neuron cultures are supplied with serum-free B27 (NBMB27) neurobasal media, the necessity to introduce serum into the system for the sake of the co-cultured endothelial cells warranted further investigation[21, 22]
The supplied media were formulated in the following categories: Neurobasal media (NBM) with FBS; Neurobasal media without FBS; and endothelial growth medium (EGM)
Summary
The proposed platform employs a system of two separate media microchannels to independently emulate highly localized internal and external vascular microenvironments. The two media microchannels, designated as the Vascular Channel (VC) and the Neural Channel (NC), supply their respective co-culture tissues independently of one another, and can serve as the microenvironment of the outside and the inside of the BBB respectively. The VC connects to the inner lumen of the vascular network, while the NC supplies the neural cells directly attached to the vascular network. The Vascular Network Channel (VNC) generated by this platform exhibits direct contact between neural and vascular tissues and a corresponding low permeability characteristic of in vivo BBB (Fig. 1a), suggesting that the dual-channel co-culture method has broad applications in vascular and neural tissue network construction
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