Mechanical Signaling in the Microenvironment Regulates the Differentiation of Dental Pulp Stem Cells: A Novel Strategy For Pulp-Dentin Complex Regeneration.

Dental pulp stem cells (DPSCs) have garnered significant attention in regenerative dental medicine due to their robust self-renewal capacity and multi-lineage differentiation potential. Their ability to undergo odontogenic differentiation and facilitate dentin matrix formation is fundamental to the regeneration of a structural and functional dental pulp-dentin complex. Recent advances in understanding the cellular mechanical microenvironment have revealed that DPSCs can precisely perceive mechanical cues—such as matrix stiffness, elastic modulus, and fluid shear stress—within both native odontogenic niches and engineered biomimetic microenvironments. These mechanical signals are transduced into intracellular biochemical responses through mechanotransduction pathways, thereby directing lineage commitment toward odontogenic, angiogenic, and other fates, and ultimately influencing tissue regeneration outcomes. Consequently, by modulating static mechanical properties and dynamic mechanical loading within the DPSC microenvironment, specific mechanical signals can be precisely delivered to guide directed differentiation and promote organized regeneration of the pulp-dentin complex. This review summarizes the mechanisms of mechanotransduction and their roles in promoting DPSC differentiation, highlights recent progress in the design of biomaterials for pulp-dentin complex regeneration based on mechanical signaling, offers new perspectives for the development of bioactive materials, and discusses current challenges and future directions in the field.