Integrating perfusable vascular networks with a three-dimensional tissue in a microfluidic device

Integr Biol (Camb). 2017 Jun 19;9(6):506-518. doi: 10.1039/c7ib00024c.


Creating vascular networks in tissues is crucial for tissue engineering. Although recent studies have demonstrated the formation of vessel-like structures in a tissue model, long-term culture is still challenging due to the lack of active perfusion in vascular networks. Here, we present a method to create a three-dimensional cellular spheroid with a perfusable vascular network in a microfluidic device. By the definition of the cellular interaction between human lung fibroblasts (hLFs) in a spheroid and human umbilical vein endothelial cells (HUVECs) in microchannels, angiogenic sprouts were induced from microchannels toward the spheroid; the sprouts reached the vessel-like structures in a spheroid to form a continuous lumen. We demonstrated that the vascular network could administer biological substances to the interior of the spheroid. As cell density in the spheroid is similar to that of a tissue, the perfusable vasculature model opens up new possibilities for a long-term tissue culture in vitro.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blood Vessels / cytology
  • Blood Vessels / growth & development*
  • Coculture Techniques
  • Equipment Design
  • Fibroblasts / cytology
  • Fluorescent Dyes
  • Human Umbilical Vein Endothelial Cells
  • Humans
  • Lab-On-A-Chip Devices*
  • Lung / cytology
  • Neovascularization, Physiologic*
  • Perfusion
  • Spheroids, Cellular / cytology
  • Tissue Culture Techniques
  • Tissue Engineering / instrumentation*
  • Tissue Engineering / methods


  • Fluorescent Dyes