Decoupling the Amplitude and Wavelength of Anisotropic Topography and the Influence on Osteogenic Differentiation of Mesenchymal Stem Cells Using a High-Throughput Screening Approach.

High-throughput screening (HTS) methods based on anisotropically topography gradients have been broadly used to investigate the interactions between cells and biomaterials. However, few studies focus on the optimum parameters of topography for osteogenic differentiation because the structures of topography are complex with multiple combinations of parameters. In this study, we developed polydimethylsiloxane (PDMS)-based wrinkled topography gradients (amplitudes between 144 and 2854 nm and wavelengths between 0.91 and 13.62 μm) and decoupled the wavelength and amplitude via imprinting lithography and shielded plasma oxidation. The PDMS wrinkle gradient was then integrated with the bottomless 96-well plate to constitute the wrinkled HTS platform, which consists of 70 different wrinkle parameters. From the in vitro culture of bone marrow stem cells, it was observed that aligned topography has an important influence on the macroscopic cell behavior (i.e., cell area, elongation, and nucleus area). Furthermore, the optimum wrinkle parameter (wavelength: 1.91 μm; amplitude: 360 nm) for osteogenic differentiation of stem cells was determined via this screening plate approach. This screening platform is not only beneficial for a better understanding of the interactions between topography and biomaterials but also advances the development of bone tissue engineering developments.