Abstract
The ECM therefore plays an important role not only in the maintenance of the structural integrity of tissues but equally during tissue regeneration where the interplay between cells and ECM is altered as a consequence of injury. [3,4] In regeneration, human mesenchymal stem cells (hMSCs) from the bone marrow stroma are believed to play an important role due to their ability for self-renewal and differentiation into different mature cells like osteoblasts, adipocytes and chondrocytes. [5] Numerous studies have shown that the mechanical properties of the cell's microenvironment, such as the substrate stiffness, have a fundamental effect on hMSC cell fate and function and impact tissue regeneration. [6-9] Recently, evidence is rising that the geometrical properties of the cell's environment also play an important role as regulators of cell behavior. [10-19] Using geometric features, such as pore geometry, as a cue to direct tissue regeneration is compelling since it may allow a biomaterial to steer cell function purely by its shape and hereby contribute to tissue regeneration. Although geometry guided cell behavior has been studied extensively on 2D substrates, the knowledge of how 3D geometry affects cell behavior is strongly limited. A Signals from the microenvironment around a cell are known to influence cell behavior. Material properties, such as biochemical composition and substrate stiffness, are today accepted as significant regulators of stem cell fate. The knowledge of how cell behavior is influenced by 3D geometric cues is, however, strongly limited despite its potential relevance for the understanding of tissue regenerative processes and the design of biomaterials. Here, the role of surface curvature on the migratory and differentiation behavior of human mesenchymal stem cells (hMSCs) has been investigated on 3D surfaces with well-defined geometric features produced by stereolithography. Time lapse microscopy reveals a significant increase of cell migration speed on concave spherical compared to convex spherical structures and flat surfaces resulting from an upward-lift of the cell body due to cytoskeletal forces. On convex surfaces, cytoskeletal forces lead to substantial nuclear deformation, increase lamin-A levels and promote osteogenic differentiation. The findings of this study demonstrate a so far missing link between 3D surface curvature and hMSC behavior. This will not only help to better understand the role of extracellular matrix architecture in health and disease but also give new insights in how 3D geometries can be used as a cell-instructive material parameter in the field of biomaterial-guided tissue regeneration.