Abstract
Biological gradients are more than linear, one-dimensional phenomena—they often manifest radial geometries superimposed over tissue features and in turn, elicit a spatial response. In wound healing, injury to tissue produces a hypoxic gradient towards the center of the wound, and wound cells respond to this by secreting growth hormones to promote healing. Despite this spatial element in tissue hypoxia, most in vitro hypoxia techniques rely on linear, diffusion-based gradients of limited dimensions. To demonstrate a large area, radial hypoxia gradient, a concentric spiral microfluidics was devised to balance oxygen diffusion against nitrogen convection. The devices were fabricated using only a simple robotic cutter and soft lithography. With these spirals, spatial gradients of 3–15 % oxygen were delivered to fibroblast cells seeded across a gas-permeable membrane to modulate VEGF secretions. This technique opens the door for more studies on hypoxic gradients in wound healing and a number of tissue oxygen applications.
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Acknowledgments
This work was supported by the University of Michigan Dearborn Faculty Startup Fund, SEED Fund, and Graduate Student Research Fund. We thank Dr. Gargi Ghosh for donating fibroblast cells used in this study. We thank Dr. Nilay Chakraborty’s help on the oxygen transport.
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The authors declare no competing financial interest.
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Li, Z., Hu, D., Zhao, Z. et al. Balancing oxygen diffusion and convection in spiral microfluidics to mimic radial biological gradients. Biomed Microdevices 17, 14 (2015). https://doi.org/10.1007/s10544-014-9922-9
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DOI: https://doi.org/10.1007/s10544-014-9922-9