Combined effects of multi-scale topographical cues on stable cell sheet formation and differentiation of mesenchymal stem cells.

To decipher specific cell responses to diverse and complex in vivo signals, it is essential to emulate specific surface chemicals, extra cellular matrix (ECM) components and topographical signals through reliable and easily reproducible in vitro systems. However, the effect of multiple cues such as micro-hole/pillar architectures under a common and easily tunable platform remains unexplored. Recently we have demonstrated the positive influence of surface chemical modification of polydimethylsiloxane (PDMS) surfaces on directing long-term adhesion, viability and potency of hMSCs. In this study, we include biophysical signals from diverse surface topographical elements along with biochemical influences to develop a holistic understanding of hMSC responses in complex tissue-like niches. We report the influence of chemically modified PDMS structures encompassing hole-, pillar- and groove-based multi-scale architectures on hMSC morphology, adhesion, proliferation and differentiation. The inclusion of hole and pillar features resulted in enhanced adhesion and proliferation of hMSCs. These effects were more pronounced with the inclusion of grooves, which resulted in the highest osteogenic differentiation among other substrates. Our study provides an additional basis for the chemical/physical regulation of hMSC behavior within controlled biomimetic architectures with an aim to foster efficient tissue regeneration strategies.