Nanotopography-guided cellular mechanobiology: Mechanotransduction pathways and applications in tissue engineering

Nanotopography has emerged as a powerful tool for regulating cellular behavior through mechanotransduction. This review explores how engineered nanoscale features, including grooves, ridges, and pillars, modulate integrin clustering, cytoskeletal organization, and nuclear signaling via YAP/TAZ and PIEZO1, ultimately influencing cell fate, epigenetic remodeling, and tissue regeneration. We discuss the hierarchical pathways linking extracellular topographies to chromatin regulation, emphasizing cell-type–specific responses in mesenchymal stem cells, fibroblasts, and myoblasts. Advances in nanofabrication, including electron-beam lithography, nanoimprinting, electrospinning, and self-assembly, have enabled reproducible topographical platforms to mimic extracellular matrix geometry. These have been applied across diverse biomedical fields, including bone, nerve, skin, and liver tissue engineering, as well as for implant surface optimization. Despite the growing clinical potential of these, challenges remain in topography standardization, biomarker development, sterilization resilience, and in vivo integration. Future directions include AI-driven design, dynamic topography, and integrated physical–biochemical cue delivery. Together, these strategies will drive next-generation mechanotherapeutic materials and deepen our understanding of cell–material interactions at the nanoscale.