| Summary: | Abstract Efficient bone repair relies on biomaterials that exhibit superior biocompatibility and enhanced osteogenic capabilities. In recent, micropatterning technology has emerged as a robust strategy for directing stem cell differentiation, offering a notable shift from traditional chemical induction or genetic modification methods by providing environmental cues to regulate cellular behavior. Among the various types of microstructures, micropillars have garnered significant attention due to their adjustable properties and high‐throughput experimental capabilities. These structures play a pivotal role in governing nuclear deformation and deciphering cellular responses to biomechanical cues. In this comprehensive review, the influence of micropillars on mesenchymal stem cells (MSCs), drawing upon two decades of research findings is critically assessed. The study comprehensively evaluates how micropillar substrates impact crucial cellular processes such as deformation, migration, adhesion, and ultimately, MSC fate determination toward an osteogenic lineage. By synthesizing and analyzing past studies, the potential regulatory mechanisms through which micropillars modulate MSC behavior are aimed to be elucidated. Furthermore, the utility of micropillars as a cutting‐edge biomechanical detection tool and platform for investigating cellular behaviors is explored. By projecting future applications, the review highlights the growing significance of micropillars in the dynamic field of biomechanics, underscoring their transformative potential in tissue engineering and regenerative medicine.
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