3D multi-chamber fluidic systems for analysis of angiogenesis in biomaterials: development, characterization and applications

The cellular processes leading to capillary morphogenesis depend on external stimuli, in particular flow and morphogen gradients. Several devices have been designed to study these interactions in vitro. However, most of these devices allow a single experiment at a time, making it difficult to compare multiple conditions, which is needed for most biology experiments. Furthermore, it can be of great interest to use the same set of cells. Here we present two multi-chamber interstitial flow systems for side-by-side culture with the capability to follow the dynamics of individual cells. While a 9-chamber system was designed for cell culture or co-culture under radial flow, a multi-chamber migration assay allows studying cell migration into biomaterials under a constant flow profile. The effects of flow on lymphatic and blood endothelial cell morphology, as well as the extent of organization induced by VEGF, were observed. In addition, we demonstrated the feasibility of studying cell-cell interactions as well as cell-matrix interactions in a fibroblast and tumor cell co-culture. The two systems presented will allow for the study of interstitial flow and its effects