Mechanomedicine-guided mechanical preconditioning of dental-derived stromal cells for tissue regeneration

Dental-derived stromal cells (DSCs), including periodontal ligament stem cells, dental pulp stem cells, stem cells from the apical papilla, and stem cells from human exfoliated deciduous teeth, are promising candidates for oral and craniofacial regeneration because of their accessibility, expandability, and functional relevance to periodontal, dentin-pulp, bone, and neurovascular repair. However, the therapeutic performance of DSC-based products remains inconsistent, partly because conventionally expanded cells may be insufficiently adapted to the mechanical cues encountered in vivo. In this Review, we present mechanical preconditioning as a mechanomedicine-guided strategy for ex vivo functional priming of DSCs. We summarize how major DSC populations respond to defined biophysical cues such as tensile and compressive forces, fluid shear stress, hydrostatic pressure, matrix stiffness, and surface topography, and we discuss the principal mechanotransduction pathways involved. We further outline representative quantitative loading windows and consider how these may support subtype-specific and indication-specific preconditioning design. Finally, we highlight key translational barriers, including stromal cell heterogeneity, donor variability, senescence, uncertain persistence of mechanically induced states, safety concerns, and the lack of standardized manufacturing workflows. Overall, clinical translation will require a shift from descriptive mechanobiology toward parameter-defined, indication-specific, and good manufacturing practice-compatible preconditioning strategies for DSC-based regeneration.