Sources of dentin-pulp regeneration signals and their modulation by the local microenvironment

Many aspects of dentin pulp tissue regeneration have been investigated, and it has been shown that dentin pulp has a high regeneration capacity. This seems to be because of the presence of progenitor cells and inductive regeneration signals from different origins. These signals can be liberated after the acidic dissolution of carious dentin as well as from pulp fibroblasts and endothelial cells in cases of traumatic injury. Thus, both carious lesions and pulp cells provide the required mediators for complete dentin-pulp regeneration including reparative dentin secretion, angiogenesis, and innervation. Additionally, all dentin pulp insults including carious "infection," traumatic injuries, application of restorative materials on the injured dentin pulp, and subsequent apoptosis are known activators of the complement system. This activation leads to the production of several biologically active fragments responsible for the vascular modifications and the attraction of immune cells to the inflammatory/injury site. Among these, C5a is involved in the recruitment of pulp progenitor cells, which express the C5a receptor. Thus, in addition to dentin and pulp cells, plasma should be considered as an additional source of regeneration signals.