Propagation-Based Phase Contrast Computed Tomography as a Suitable Tool for the Characterization of Spatial 3D Cell Distribution in Biomaterials

The 3D structural investigation of soft tissue samples under near physiological conditions is challenging as most established techniques require embedding, staining, or cutting samples. Such manipulations can induce artifacts or result in a tremendous workload by, e.g., the preparation of multiple 2D images to retrieve the volume information. A non-invasive technique allowing to image the soft tissue in a 3D fashion is propagation-based phase contrast computed tomography. We explore the methods' unique properties to assess the 3D distribution and size of human chondrocytes within collagen scaffolds in a liquid environment without embedding. To seek if the identification of differences in cell distribution is possible, we have seeded cartilage cells on collagen scaffolds that were unstimulated or stimulated by alternating electric fields for 7 days. Analysis of the 3D cell distributions reveals that the migration depth of the chondrocytes into the scaffold is nearly doubled along with the total number of cells due to the applied electric field. Further analysis shows no specific size distribution of the chondrogenic cells. Our results indicate that propagation-based phase contrast computed tomography is a suitable tool to determine the 3D distribution of cells within a biomaterial investigated under aqueous conditions.