Cell pattern formation controlled by microscale interfaces

Regenerative medicine aims at cell-based therapy to rebuild the non-regenerative tissue. To mimic the tissue development, supportive scaffolds have been intensively studied to allow cell attachment, migration, and to control delivery of essential factors. However, tissue is characterized by self-organization, which can limit the attempts to directly control the tissue development. Previously we applied local substrate discontinuity to cultured vascular stem cells (VSCs), which spontaneously aggregate into periodic multicellular patterns resembling normal tissue architectures [1], and showed that the substrate interface can led to change of pattern morphology via their inherent self-organization [2]. In the present study, we study the effects of 1) geometrical interface (micromachined surface geometrical step), 2) chemical interface (substrate discontinuity), and 3) cellular interface (stepwise cell distributions) to the development of global pattern formations. The findings suggest that cells sense the local stimuli and unfold it into multicellular structures, providing a new way for cell-based engineering of tissue architecture.