Pneumatic mold-aided construction of a three-dimensional hydrogel microvascular network in an integrated microfluidics and assay of cancer cell adhesion onto the endothelium

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A pneumatic microchannel network (PμCN) fabrication method for producing a three-dimensional microvascular system in an integrated microfluidic device is described. The spatial dynamics of the PμCN profile is systematically characterized and quantitatively analyzed. A microvessel network-embedded hydrogel scaffold is constructed using in situ pneumatic actuation of the PμCN and collagen polymerization. The endothelium-containing microvasculature, which has high cell viability and typical vascular features, was formed by seeding and cultivating human umbilical vein endothelial cells (HUVEC-C). Furthermore, a quantitative investigation of the adhesive interactions between breast cancer cells and endothelial cells was performed with vascular tissue-mimicry in the hydrogel-supported endothelial network using human breast cancer cells (MDA-MB-231) and HUVEC-C cells. The results show signal-promoted and region-preferred adhesion of cancer cells in the established microvascular network. The PμCN can be applied as an active microfluidic molding component for convenient and robust reproduction of microvasculature in vitro. PμCN application can be valuable in monitoring and investigating blood vessel-involved physiologic/pathologic processes. Moreover, this method will facilitate controllable parenchymal tissue organization and construction for tissue engineering as well as subsequent applications for clinical medicine.

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This work was supported by the National Natural Science Foundation of China (Grant nos. 20975082, 21175107, and 31100726), the Ministry of Education of the People’s Republic of China (Grant no. NCET-08-0464), and the Northwest A&F University.

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Correspondence to Jinyi Wang.

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J.-C. Wang and Q. Tu contributed equally to this work.

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Wang, J., Tu, Q., Wang, Y. et al. Pneumatic mold-aided construction of a three-dimensional hydrogel microvascular network in an integrated microfluidics and assay of cancer cell adhesion onto the endothelium. Microfluid Nanofluid 15, 519–532 (2013) doi:10.1007/s10404-013-1172-2

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  • Microvasculature
  • Pneumatic membrane
  • Microfluidics
  • Cancer cells
  • Endothelial cells