Abstract
Free-form constructs with three-dimensional (3D) microporosity were fabricated by two-photon polymerization inside the closed microchannel of an injection-molded, commercially available polymer chip for analysis of directed cell migration. Acrylate constructs were produced as woodpile topologies with a range of pore sizes from 5 × 5 μm to 15 × 15 μm and prefilled with fibrillar collagen. Dendritic cells seeded into the polymer chip in a concentration gradient of the chemoattractant CCL21 efficiently negotiated the microporous maze structure for pore sizes of 8 × 8 μm or larger. The cells migrating through smaller pore sizes made significantly more turns than those through larger pores. The introduction of additional defined barriers in the microporous structure resulted in dendritic cells making more turns while still being able to follow the chemoattractant concentration gradient.
Highlights
The ideal construct for migration analysis should (a) result in cell migration behavior that functionally resembles the in vivo behavior as closely as possible, (b) be highly4800 | Lab Chip, 2013, 13, 4800–4809Paper reproducible to enable reliable interpretation of the cell responses, and (c) support the presence of a stable concentration gradient of signaling molecules across the construct to perform directed cell migration studies
Free-form constructs with three-dimensional (3D) microporosity were fabricated by two-photon polymerization inside the closed microchannel of an injection-molded, commercially available polymer chip for analysis of directed cell migration
Woodpile structures were chosen as the starting point for designing and investigating directed cell migration in 3D, since they provide the cells with multiple straight pathways at perpendicular orientations in close vertical proximity (Fig. 3)
Summary
The ideal construct for migration analysis should (a) result in cell migration behavior that functionally resembles the in vivo behavior as closely as possible, (b) be highly4800 | Lab Chip, 2013, 13, 4800–4809Paper reproducible to enable reliable interpretation of the cell responses, and (c) support the presence of a stable concentration gradient of signaling molecules across the construct to perform directed cell migration (chemotaxis) studies. The ideal construct for migration analysis should (a) result in cell migration behavior that functionally resembles the in vivo behavior as closely as possible, (b) be highly. In vitro microenvironments may be designed with varying degrees of microstructural complexity to explore cellular navigation abilities, possibly after the addition of natural extracellular components to provide biochemical and ultrastructural signaling. Designs inducing the most in vivo-like migration can be selected for larger scale fabrication to be used in cell preparation optimization or cell migration validation. Both applications are of relevance to cell-based immunotherapy by dendritic cells as we target here. The final constructs should permit optical visualization of the migrating cells to analyze their individual detailed migration pathways within a stable concentration gradient maintained for hours to days
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
