Engineering-Aligned 3D Neural Circuit in Microfluidic Device.
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.
Division of WCU (World Class University) Multiscale Mechanical Design, School of Mechanical and Aerospace Engineering, Institute of Advanced Machinery and Design, Seoul National University, Seoul, 151-744, South Korea.
Seokyoung
S
Bang
Division of WCU (World Class University) Multiscale Mechanical Design, School of Mechanical and Aerospace Engineering, Institute of Advanced Machinery and Design, Seoul National University, Seoul, 151-744, South Korea.
Sangcheol
S
Na
Interdisciplinary Program in Neuroscience, Seoul National University, Seoul, 151-744, South Korea.
Jae Myung
JM
Jang
Center for Functional Connectomics, Korea Institute of Science and Technology (KIST), Seoul, 136-791, South Korea.
Jinhyun
J
Kim
Division of WCU (World Class University) Multiscale Mechanical Design, School of Mechanical and Aerospace Engineering, Institute of Advanced Machinery and Design, Seoul National University, Seoul, 151-744, South Korea.
Noo Li
NL
Jeon
D000818:Animals; D003094:Collagen / Q000494:pharmacology; D003432:Cross-Linking Reagents / Q000494:pharmacology; D004338:Drug Combinations; D005109:Extracellular Matrix / Q000378:metabolism; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000494:pharmacology; D007797:Laminin / Q000494:pharmacology; D044085:Microfluidics / Q000295:instrumentation*; D016501:Neurites / Q000187:drug effects / Q000378:metabolism; D009474:Neurons / Q000378:metabolism*; D011509:Proteoglycans / Q000494:pharmacology; D017207:Rats, Sprague-Dawley; D023822:Tissue Engineering / Q000295:instrumentation* / Q000379:methods*
D003432:Cross-Linking Reagents; D004338:Drug Combinations; D007797:Laminin; D011509:Proteoglycans; C059485:matrigel; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D003094:Collagen
3D neuron cultures; axon fasciculation; in vitro neural circuit; microfluidics