• Biophysical cues such as substrate stiffness and fluid shear stress are pivotal in the pathogenesis of dental diseases like caries, periodontitis, and dentin hypersensitivity.
• Exosomes derived from dental stem cells inherit biophysical signals and offer a promising cell-free therapy for dental regeneration, overcoming limitations of direct stem cell transplantation.
• Biophysical cues regulate exosome biogenesis, release, and uptake, providing a mechanism to enhance their therapeutic efficacy in dental disease treatment.
• This review highlights the potential of biophysical cue-regulated exosomes as novel targets for dental regenerative medicine, bridging mechanobiology and exosome-based therapy.