# A Molecular View on Biomaterials and Dental Stem Cells Interactions: Literature Review
## 4 Dental Stem Cells and Biomaterial Interactions
### Mechusensors in Dental Stem Cells
(2015) [88] reported that, in human bone marrow MSCs subjected to stretching or suction, TRPM7 activation appears to be independent of actin polymerization disruption since suction-induced TRPM7 activation was not abolished [88]. In DPSCs, research has also focused on TRPM7 and osteogenesis. For example, [PERSON] et al. (2013) [87] reported that TRPM7 participates in the pulp-repair process through the regulation of proliferation, migration, and osteogenic differentiation of DPSCs, while TRPM4 is necessary for adipogenesis in stem cells of DFSCs in rats [87]. The authors agree that the activation of TRPM gives rise to the release of Ca\({}^{2+}\) mediated by IP\({}_{3}\) type 2 (IP\({}_{3}\)R2) from the endoplasmic reticulum, amplifying Ca\({}^{2+}\) signaling and inducing osteogenesis through the activation of the transcription factor NFATc1 [88; 89; 90]. Taking theseresults together, the data suggest that MICs are important molecular sensors. However, studies have only focused on DPSCs and osteogenesis. It would be interesting to see if a similar regulatory pathway is conserved in other types of DT-MSCs. Other important mechanosensors are macromolecular complexes that include cytoskeletal proteins (microtubules, \(f\)-actin microfilaments, intermediate filaments, and actin-linking proteins), nucleoskeletal-related proteins (SUN1, SUN2, lamins), adherens junctions (cadherins, \(\alpha\)-catenin, \(\beta\)-catenin), focal adhesion proteins (vinculin), integrins, and ECM-related proteins (fibronectin) [57; 58]. These mechanosensors turn on the rearrangement of molecular components by activating several intracellular signaling pathways that are involved in growth, cell proliferation, and the regulation of gene expression (Figure 3). The cytoskeleton plays important roles in cell morphology, adhesion, growth, and signaling [91]. In this context, stem cells alter their cytoskeleton in response to mechanical  
Figure 3: Schematic diagram for signals and signaling pathways in DT-MSCs during their interaction with biomaterials. DT-MSCs are an entity interconnected by multiple molecular components during their interaction with biomaterials. Mechanical stimulus or signals from the biomaterials are perceived in the cell membrane, which activates various proteins such as Piezo channel or TRPM, that trigger the influx or release of Ca2+ which have strong connection with cell signaling involved in the proliferation and differentiation. Therefore, cell-cell (cadherins and gap junction) and cell-biomaterial communication is facilitated by remodeling the cytoskeleton (actin) and favoring focal adhesion sites (FAK) that activate signaling pathways (PI3K, AKT, mTOR, ERK, YAP/TAZ) that regulate the behavior of stem cells, improving their cellular response (proliferation or differentiation) in the presence of biomaterials. ER: endoplasmic reticulum; PI3K: Phosphoinositide 3-kinases, ERK: extracellular signal-regulated kinase; FAK: focal adhesion kinase; FT: transcription factor; YAP: Yes-associated protein; TAZ: Transcriptional coactivator with PDZ-binding motif; AKT: Ser/Thr protein kinase; RAS: GTPases protein. forces that cause cell reorganization through actin polymerization and microtubule assembly or by disassembling cytoskeletal components and their ECM junctions [75]. Topography of biomaterials is a promising approach to guide cytoskeleton behavior and differentiation in stem cells. Several works have focused on analyzing how the topographic signals (macro, micro, or nanoscale) of biomaterials affect the behavior of components of the cytoskeleton in DT-MSCs. For example, [PERSON] et al. (2019) [92] determined that the topographic signals of a poly(lactic-co-glycolic acid) bilayer (PLGA) change F-actin alignment and DPSCs morphology by modulating Yes-associated protein (YAP) signaling to control osteogenic differentiation/odontogenicity [92]. [PERSON] et al.