Control of invasion direction of cancer cells using hierarchically patterned hydrogel sheets

摘要

In this study, we propose a new cell culture system using microengineered hierarchical hydrogel sheets, which enables guidance and evaluation of cancer cell invasion in 3D environments. Three-layered hydrogel sheets, which encapsulated cancer cells in the patterned middle layer, were placed on a collagen hydrogel. Because the direction of nutrition is only from the collagen gel to the sheets, cell invasion was guided to the basal collagen gel as in the case of epithelial tissues. In the experiment, we fabricated hierarchically-engineered alginate-based hydrogel sheets using multi-laminated microfluidic devices, and clearly demonstrated that embedded cancer cells invasion was guided to the collagen layer. By counting the number of cells reaching the collagen gel, the evaluation of cell invasion would become possible. The proposed system would be useful because it realizes facile and precise cell migration assays in 3D platforms.