Microengineering of Collagen Hydrogels Integrated into Microfluidic Devices for Perfusion Culture of Mammalian Cells

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Abstract
Collagen-based hydrogels are widely used for three-dimensional (3D) culture of mammalian cells because of their high cell-activating characteristis. However, techniques for preparing of cell-embedding collagen hydrogels with micrometer-size precision in perfusable, microfluidic devices have not been fully developed. In this study, we propose a facile strategy enabling microfabrication of collagen hydrogels in microfluidic devices. We used phosphate particle-embedding polydimethylsiloxane (PP-PDMS) as a gelation agent, which neutralizes the acidic collagen soltuion. The collagen solution near the surface of the PP-PDMS is selectively gelled. We fabricated micropatterns and tubular structures made of collagen hydrogel, both of which were used for perfusion culture of mammalian cells encapsulated in the hydrogel matrix. The presented approach would be applicable to various types of cell culture experiments.