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The Development and Functional Validation of Engineered Microvessels Using Microfluidic Devices
Author(s) -
Xu Sulei,
Li Xiang,
Liu Yuxin,
He Pingnian
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.791.2
Subject(s) - microvessel , polydimethylsiloxane , microfluidics , microchannel , biomedical engineering , nanotechnology , in vivo , chemistry , umbilical vein , materials science , in vitro , biophysics , angiogenesis , biology , biochemistry , medicine , microbiology and biotechnology , cancer research
Microfluidic technologies have enabled in vitro studies to closely simulate the in vivo microvessel environment with sufficient complexity. However, the lack of functional validation has prevented their broader application for biomedical research. The objective of this study is to develop in vitro microvessel network and compare their biological responses with intact microvessels. Standard photolithography was used for the master mold fabrication and polydimethylsiloxane soft lithography was used for the microfluidic microchannel network fabrication. The microchannels used for this study has three level branching network with the smallest diameter at 100 mm. Primary human umbilical vein endothelial cells were successfully cultured along the entire inner surface of the microchannel network in 3‐4 days under a constant flow of culture media. Confocal immunofluorescence imaging shows well‐developed VE‐cadherin at EC junctions throughout the channels and the cell morphology is close to ECs in intact venules. We also successfully loaded calcium and nitric oxide indicator, Fura‐2 and DAF‐2, respectively, in ECs forming the microvessel network and measured ATP‐induced changes in EC [Ca 2+ ] i and nitric oxide production. The results were comparable to those derived from individually perfused intact venules. With the validation of the functionalities of the cultured microvessels, our microfluidic microvessel model demonstrates a great potential for biological applications and bridging the gaps between in vitro and in vivo microvascular research. Supported by HL56237, DK097391 and NSF 1227359.