Microenvironment-mediated stem cell fate in periodontal tissue remodeling and repair

The cellular microenvironment is an integrated complex of the extracellular matrix, cells and extracellular fluids containing numerous bioactive molecules. It is widely acknowledged that the periodontal microenvironment exerts profound effects on adjacent stem cells, affecting tissue remodeling and repair. For instance, the physiological microenvironment maintains stemness and supports tissue-specific differentiation of mesenchymal stem cells (MSCs), whereas pathological inflammation resets programmed cell fate, increases the secretion of proinflammatory factors, and may even induce MSC apoptosis. The normal remodeling or repair process is therefore dysregulated, and inflammatory conditions worsen. Modulating the stem cell-based microenvironment appears to be an effective strategy for periodontal regeneration. In this review, five types of MSCs involved in periodontal tissue remodeling and repair are introduced. Subsequently, we discuss the impact of various periodontal microenvironments on MSC fate and further summarize the latest biomaterials for use in periodontal regeneration from the aspect of microenvironmental cues. The use of multiple material design strategies to modify the inflammatory microenvironment offers valuable insights for future advancement of material-guided periodontal regeneration under pathological conditions.