# A Molecular View on Biomaterials and Dental Stem Cells Interactions: Literature Review
## 4 Dental Stem Cells and Biomaterial Interactions
### Mechusensors in Dental Stem Cells  
Currently, the design of biomaterials with specific characteristics is a novel approach for evaluating the effect of chemical, physical or topographic changes in stem cells during their proliferation and differentiation under in vitro conditions. The reason for this is that stem cells are very sensitive to forces and can convert mechanical stimuli into a chemical response [77]. There is much evidence that DPSCs are mechanosensitive cells and capable of recognizing physical and mechanical signals during their differentiation process. In this context, the participation of mechanosensors, such as mechanosensitive ion channels, cytoskeleton proteins, and assembly proteins, has been recognized in DPSCs. Mechanosensitive ion channels (MICs) are receptors that convert extracellular mechanical force into intracellular biochemical information. However, how do the channels mediate these sensations and turn them into a stimulus? Does this occur through direct or indirect activation of the channel? To answer this question, [PERSON] et al. (2016) [78] proposed two scenarios. The first is that mechanical force is released into the channel by lipid bilayer tension, generating a hydrophobic mismatch that helps the channel open. In the second, the participation of accessory proteins (for example, those of the cytoskeleton or the components of the ECM) has been proposed, and mechanical stress transmitted by the cytoskeleton causes Ca\({}^{2+}\) release from the endoplasmic reticulum via the inositol trisphosphate receptor (IP\({}_{3}\)R) [78]. There are reports of MICs that play an important role in the transduction of mechanical forces in the activation of signaling pathways involved in cell proliferation and differentiation in stem cells. In this context, two MICs have been recognized in DPSCs: Piezo proteins and members of the transient receptor potential (TRP) channel family. The Piezo channel is a three-bladed helix-shaped trimeric complex that includes two subtypes: Piezo1 and Piezo2 [79]. In stem cells, these proteins play an important role in shear stress and traction signals during their proliferation [80; 81; 82]. Several researchers agree that when the Piezo protein is activated, there is an influx of Ca\({}^{2+}\)[65]. However, there is still controversy about whether the integrity of the cytoskeleton is affected by the activity of the channel in response to mechanical stimuli. The role of Piezo proteins in DPSCs has been studied through adjuvant therapies for the repair of dental tissues. An example of this is the use of low-intensity pulsed ultrasound (LIPUS) recognition therapy employed in dental tissue repair [64]. In cells, LIPUS acts as a mechanobiological stimulus that activates various signaling pathways that regulate cell proliferation and differentiation. For example, [PERSON] et al. (2015) [83] investigated the presence of Piezo1 and Piezo2 in DPSCs and PDLSCs and their involvement in LIPUS-associated proliferation and MAPK signaling. The authors demonstrated that DPSC proliferation was associated with LIPUS stimulation by activating MAPK signaling, while in PLSCs, it could occur through another mechanism [83]. Another study by [PERSON] et al. (2020) [84] examined the role of Piezo1 in ATP release in DPSCs migration in vitro. The authors reported that the activation of Piezo1 induces the release of ATP, modulating the activity of P2 receptors and inducing the activation of proline-rich tyrosine kinase 2 (PYK2) and MEK/ERK. Another ionic channel broadly expressed in DPSCs is the transient receptor potential (TRP) channel, including transient receptor potential melastatin types 4 and 7 (TRPM4 and TRPM7, respectively) [85; 86; 87]. TRPM controls Ca\({}^{2+}\) signals and is sensitive to mechanical stimuli, such as patch-clamp pipette suction and patch-clamp pipette stretching. [PERSON] et al.