Surface Topography Regulates Osteogenic Differentiation of MSCs via Crosstalk between FAK/MAPK and ILK/β-Catenin Pathways in a Hierarchically Porous Environment

The response of mesenchymal stem cell (MSCs) to elaborate microarchitectured topographies in three-dimensional environment and the underlying molecular mechanism remain poorly understood. Here, with hierarchical mesoporous bioactive glass (MBG) scaffolds as substrate model, we show the effects of specific, elaborate microtextured topographies (micrograiny, microporous and hybrid micrograiny/microporous surface) on MSCs osteogenesis and the molecular mechanism involved. With a similar size and density, the microporous surface was more favorable for the MSC osteogenesis, and the hybrid micrograiny/microporous surface exhibited a synergetic effect. All the microscaled topographies facilitated expression of integrin subunits, focal adhesion complexes, and up -regulated FAK/MAPK and ILK/beta-catenin signaling pathways. Separately blocking FAK/MAPK and ILK/beta-catenin cascade dramatically attenuated the heightened beta-catenin signaling, and the phosphorylation of ERK1/2 and P38, respectively, indicating a typical crosstalk between FAK/MAPK and ILK/beta-catenin signalings was involved. Correlating the MSCs response with the specific topographical cues, it can be inferred that the micrograiny/microporous topographies induced FAs assembly and homeostasis, and thus FAK/MAPK and ILK/beta-catenin signalings played critical role in regulating MSCs osteogenic differentiation. The findings, therefore, have significant implications in better understanding of the MSCs fate in a 3D environment and provided guidance of the development of novel biomaterial for bone regeneration.