Tuning Cellular Perception in Pluripotent Stem Cells through Topography, Stiffness, and Patterning

Pluripotent stem cells (PSCs), comprised of embryonic stem cells and induced PSCs, hold tremendous therapeutic potential. This has been driven by transformative advances in cell engineering and manufacturing, from fundamental research to clinical therapies. These innovations have come from a deeper understanding of developmental cell biology, the ability to recapitulate complex biochemical, mechanical, and topographical cues necessary for precise cell differentiation and functional maturation, and the deployment of advanced biotechnological approaches. For example, recent advances in micro‐ and nanotopographical engineering have introduced novel biomimetic approaches to enhance PSC adhesion, self‐renewal, lineage specification, and spatial organization, while continued development of PSC manufacturing—including 3D bioreactor systems, microfluidic confinement devices, and scalable automation technologies—is driving a considerable shift beyond 2D culture and biochemical signaling methods. This mini‐review examines the impact of recent developments in the application of micro‐ and nanotopographical cues in controlling core PSC fate and functions, including proliferation, adhesion, pluripotency, and differentiation. A gene expression profile can be altered by these topographical cues, and evaluate current strategies to integrate topographical control in PSC technology is highlighted.