Exploring Cellular Response to Re‐Entrant Surface Topographies

Abstract Re‐entrant microstructured surfaces present a versatile platform for modulating cellular behavior by integrating topographical and chemical cues. However, the combined influence of cap geometry and surface material of re‐entrant microstructures on cancer cell behavior remains unexplored. This study investigates the effects of cap shape (circular, triangular, and linear) and material composition (hydrophobic silicon carbide (SiC) versus hydrophilic silicon dioxide (SiO₂)) affecting the attachment, morphology, and proliferation of human breast cancer cells. Surfaces with higher solid area fractions, such as microlines and flat surfaces, consistently supported increased proliferation and spreading, while sparsely spaced geometries reduced adhesion and constrained cytoskeletal organization. SiO₂ surfaces supported enhanced responses across all designs, underscoring the role of wettability in promoting protein adsorption, integrin clustering, and activation of mechanotransduction pathways. The results revealed geometry‐dependent responses, including alignment on linear structures, focal adhesion clustering at edges, and curvature‐driven shaping of circular caps. These responses highlight the cell's ability to sense and respond to physical confinement and biochemical cues. This study extends previous work on simple micropillar arrays by demonstrating mechanosensitive behaviors that emerge when curvature and confinement are introduced through reentrant structures. The reentrant designs are also structurally stable, supporting their use in long‐term biointerface applications.