Fig 7.

Triggering of tubulogenesis in the presence of a 3D substrate architecture. HPTCs were grown to confluency on glass cover slips (A, D and G), in the wells of 24-well plates consisting of tissue culture plastic (B, E and H), and in the wells of diagnostic printed slides (C, F and I). Cover slips with a side length of 18 mm are used. The wells of 24-well plates and diagnostic printed slides are 15 mm and 2 mm in diameter, respectively. Cells on the different devices are monitored over a time period of 8 days. (A)–(C) show the confluent monolayers at day 2. The edges of the different substrates used are indicated by large arrowheads. (E, F) Monolayer retraction starts at day 3 at the edges of the wells (marked by large arrowheads) of 24-well plates and diagnostic printed slides. This leads to areas devoid of cells (marked by a small arrowhead in F). No rearrangements are observed at (D) day 3 and (G) day 8 at the edges of cover slips (marked by large arrowheads), which do not have a 3D structure. The monolayer is still intact on cover slips. By contrast, major rearrangements are noted at day 8 in the wells of (H) 24-well plates and (I) diagnostic printed slides. Formation of tubules (marked by small arrowhead in H) and myofibroblast aggregates (marked by small arrowhead in I) is observed. The wells of 24-well plates and diagnostic printed slides provide different surface chemistries and surface areas. However, in both cases, the edge is a 3D structure, in contrast to the edge of cover slips. Scale bar: 500 μm.