1 Department of Micro- and Nanotechnology, Technical University of Denmark2 Polymer Microsystems for Medical Diagnostics, Department of Micro- and Nanotechnology, Technical University of Denmark3 Polymer Microsystems for Cell Processing, Department of Micro- and Nanotechnology, Technical University of Denmark4 Risø National Laboratory for Sustainable Energy, Technical University of Denmark
Cancer is the leading cause of mortality in the developed world despite major advances in therapy in recent years. Recently cancer immune therapies have developed into promising treatments against a number of cancer types. One of the most promising is dendritic cell based cancer immunotherapy. One of the major challenges towards increasing the vaccine efficacy has been to develop maturation procedures that produce highly immunogenic dendritic cells that also demonstrate strong migratory skills. To test the migratory skills of the dendritic cells induced by the different procedures we present a versatile and easy to use chip integrated migration platform. 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 5x5 μm to 15x15 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 8x8 μm or larger. Cells migrating through smaller pore sizes made significantly more turns than through larger pores. Linear microchannels with diameters from 10 μm to 20 μm were also produced and simultaneous observations of dendritic cells migrating in the confined channels and in the fibrillar collagen were performed. Cells occluding the microchannels exhibited significantly higher migration speed than cells not occluding the channels and cells migrating in the fibrillar collagen. To more precisely mimic the mechanical and chemical properties of the tissue traversed by the dendritic cells we also present a poly (ethylene glycol) diacrylate (PEGDA) based strategy to fabricate soft 3D hydrogel scaffolds. Our experiments with the hydrogel confirm we can control the mechanical properties and introduce biochemical cues on the surface that are recognized by fibroblast cells. Finally we present initial in-chip fabrication of soft 3D constructs holding more than 80 % water.