# A Molecular View on Biomaterials and Dental Stem Cells Interactions: Literature Review
## 3 Biomaterials
### Synthetic Biomaterials  
Biomaterials of synthetic origin are used due to the growing necessity of specific characteristics of scaffolds for regenerative medicine due to the limitations of the natural biomaterials that need to be modified, the limited mechanical strength, and the difficulty of obtaining 3D scaffolds required for tissue engineering, providing cells with the necessary environment to proliferate and differentiate into a lineage-specific manner [60]. Biomaterials of synthetic origin have been widely used for the last 100 years, considering that inert materials (i.e., metal alloys) were the first to be implanted in the human body for the reconstruction of affected tissues and/or organs [61]. Currently, a range of materials are used for regenerative medicine, primarily for their characteristics, such as biocompatibility, physicochemistry, mechanical behavior, biodegradability, and modulation of cell response, among others. A variety of engineered synthetic biomaterials that are chemically and physically designed to fulfill the cellular specific needs of these critical parameters have been reported in the literature [62]. Some synthetic biomaterials, such as metallic alloys, ceramics, polymers, and hydrogels, are reported to be promotors of stem cell differentiation [63]. Regarding synthetic metal biomaterials, inert titanium alloys are commonly used in dentistry for bone tissue engineering due to their ability to induce osteogenic differentiation of dental stem cells; as reported in the literature, composite biomaterials with a polymeric matrix of polycaprolactone diol-based segmented polyurethane and titanium particles enhance the viability of pulp stem cells and osteoblasts, as it increases with the amount of titanium in composites [64]. According to [PERSON], mineral trioxide aggregates and nanohydroxyapatite could enhance the odontogenic differentiation of human dental pulp stem cells, as assessed by tracing genes characteristic of different stages of odontoblasts via qRT-PCR and calcific nodule formation evaluated by Alizarin red staining [65]. Ceramics, as bioactive glass, promote odontogenic differentiation of DPSCs; as reported by [PERSON] et al. (2020) [66] in their study, composites of mesoporous bioactive glass nanoparticles (MBNs) and graphene oxide (GO) were prepared and analyzed, and they concluded that MBN/GO promoted the proliferation and odontogenic differentiation of DPSCs [66]. In another study, composites of nano bioactive glass synthesized by the sol-gelmethod (58 SiO2:40 CaO:5P2O5) and Biodentine (Septodont, Saint Maur des Fosses, France) were prepared and tested, and they found cell adhesion and proliferation on nBG/BD nanocomposites and increased odontogenic differentiation of DPSCs, as measured by alkaline phosphatase activity after 7 and 14 days of exposure [67]. Polymers and composites of polymeric matrices are biomaterials that have been the focus of increased interest in recent years due to their capability for being designed, modified, and reinforced according to the requirements for an extensive range of therapeutic and regenerative purposes. Polymers for regenerative medicine include polyethylene glycol (PEG), polylactic acid (PLA), poly(lactic-co-glycolic acid) (PLGA), polyvinyl alcohol (PVA), and polycaprolactone (PCL) [13]. A study by [PERSON] concluded that poly(L-lactic acid) (PLLA), with recombinant human bone morphogenetic protein 2 (BMP-2), produced odontogenic differentiation of SCAP, leading to in vivo dentin regeneration [68]. Another study with PCL scaffolds reported attachment, growth, and proliferation of human SCAPs with calcification nodules detected [69]. [PERSON] et al. (2019) [70] reported that PCL-PEG-PCL/zeolite nanofibrous scaffolds produced adhesion and proliferation of DPSCs and their osteo/odontogenic differentiation and concluded that zeolite nanoparticles on PCL-PEG-PCL scaffolds could have a crucial role in osteoblastic physiology [70].