Development of a Novel Orthogonal Double Gradient for High-Throughput Screening of Mesenchymal Stem Cells-Materials Interaction

Surface gradients provide a powerful platform to accelerate multiscale design by efficiently studying of material-cell interactions to ultimately enhance function of synthetic clinical biomaterials. Herein, a novel orthogonal double gradient is reported in which surface stiffness and wettability vary independently and continuously in perpendicular directions, providing unique combinations of stiffness and wettability over a broad range (stiffness: 6-89 MPa; water contact angle: 29 degrees-90 degrees). It is found that mesenchymal stem cell behavior is nonlinearly regulated by surface stiffness and wettability. These combined stiffness and wettability properties of a material significantly affect stem cell adhesion, spreading, nucleus size, and vinculin expression. This high-throughput screening system enables elucidation of the relationships between biointerface properties and biological behavior, and thereby serves a potential tool for accelerating the development of high-performance biomaterials.