Journal
BIOMICROFLUIDICS
Volume 9, Issue 2, Pages -Publisher
AMER INST PHYSICS
DOI: 10.1063/1.4917508
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Funding
- KIST Institutional Program [2E25474, 2Z04110]
- Brain Research Program through the National Research Foundation of Korea (NRF) - Ministry of Science, ICT & Future Planning [NRF-2012M3C7A1055410]
- Basic Science Research Program through the National Research Foundation of Korea (NRF) - Ministry of Science, ICT & Future Planning [NRF-2013R1A1A2060426]
- Korea University Grant
- BioNano Health-Guard Research Center - MSIP of Korea as Global Frontier Project [H-GUARD_2014M3A6B2060524]
- Ministry of Science, ICT & Future Planning, Republic of Korea [2E25473] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
- National Research Foundation of Korea [2012M3C7A1055410, 2013M3A6B2078950, 21A20131712520] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
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We present an engineered three-dimensional (3D) in vitro brain microvasculature system embedded within the bulk of a collagen matrix. To create a hydrogel template for the functional brain microvascular structure, we fabricated an array of microchannels made of collagen I using microneedles and a 3D printed frame. By culturing mouse brain endothelial cells (bEnd.3) on the luminal surface of cylindrical collagen microchannels, we reconstructed an array of brain microvasculature in vitro with circular cross-sections. We characterized the barrier function of our brain microvasculature by measuring transendothelial permeability of 40 kDa fluorescein isothiocyanate-dextran (Stoke's radius of similar to 4.5 nm), based on an analytical model. The transendothelial permeability decreased significantly over 3 weeks of culture. We also present the disruption of the barrier function with a hyperosmotic mannitol as well as a subsequent recovery over 4 days. Our brain microvasculature model in vitro, consisting of system-in-hydrogel combined with the widely emerging 3D printing technique, can serve as a useful tool not only for fundamental studies associated with blood-brain barrier in physiological and pathological settings but also for pharmaceutical applications. (C) 2015 AIP Publishing LLC.
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