The response of dental pulp cells to BMPs suggests that the cells provide receptors for these bioactive molecules. BMP receptors (BMPR) are serine/threonine kinases, including type I receptors (BMPR-IA, BMPR-IB) and the type II receptor (BMPR-II). It was established that dental pulp cells (SHED, DPSC, fibroblasts) express BMPR-IA, BMPR-IB and BMP-II receptor. Bone Marrow Mesenchymal Stem Cells (BMMSC) have the potential to differentiate into osteoblasts, chondrocytes, and adipocytes. MSC appear to be more oriented to odontogenic rather than to osteogenic development. Polyesters of naturally occurring alpha-hydroxy acids, amino-acid based polymers, alginate and natural materials such as collagen and reconstituted extracellular matrix proteins.

Using a similar strategy as that one which was used for isolation of DPSCs, SHED demonstrated to be a population highly proliferative, composed by clonogenic cells, able to differentiate into a diversity of cell types including neural cells, adipocytes, and odontoblasts. SHED express STRO-1 and CD146, two MSC markers also present in DPSC, but SHED exhibited higher proliferation rates than DPSC. SHED differentiated into odontoblast-like cells, expressing three putative markers of odontoblastic differentiation (DSPP, DMP1, and MEPE). The obstruction of bone morphogenetic protein 2 (BMP-2) signaling inhibited the differentiation of SHED into odontoblasts. The growth factors BMP-2, BMP-4, BMP-6, BMP-7 and Gdf11 play an important role in the biology of pulp cells. Studies have shown that the expression of BMP-2 is increased during the terminal differentiation of odontoblasts, and that BMP-7 promotes the formation of reparative dentin mineralization in animal models. Dentin-derived BMP-2 is required for the differentiation of SHED into odontoblasts (Bottino et al., 2013).

MMPs and their inhibitors are metalloproteinases that comprise serralysins, astacins, adamalysins (a disintegrin and metalloproteinase domain or ADAMs), and matrixins (matrix metalloproteinases or MMPs). MMPs comprise 25 members. The established functions for MMPs include ECM cleavage of growth factor receptors, shedding of cell adhesion molecules, and activation of other MMPs, which display non-catabolic functions. ADAMs contain a distintegrin or integrin-binding domain, and a metalloproteinase domain that is similar to the conserved Zn2+-binding catalytic domain of MMPs (Hattori., et al. 2009). MMP1 facilitates keratinocyte migration over the dermal matrix by decreasing the affinity of collagen-integrin contacts. MMP7 regulates re-epithelialization by cleavage of the E-cadherin within the adherens junctions.

The tissue inhibitors of MMPs (TIMPs) include four family members, TIMP-1 to -4. TIMPs inhibit MMPs in a 1:1 inhibitor to enzyme ratio, through interaction of the N-terminal domain of the TIMP molecule with the active site of the MMP. Degradation of cell adhesion molecules by MMPs is also necessary during the repair phase, where MMP 1, 7, 9, and 10 are required for cell migration, while the addition of a synthetic metalloproteinase inhibitor leads to impaired cell migration. Resorbable materials such as alginate beads include also hyaluronate, chitosan, and collagen scaffold.

Combined altogether, or using cellular or acellular strategies constitute the successful steps for the pulp regenerative therapy, the future of endodontic treatment.