# A Molecular View on Biomaterials and Dental Stem Cells Interactions: Literature Review
## 3 Biomaterials
### Natural Biomaterials  
Research carried out in the field of biomaterials using cells of dental origin has increased in recent years. Most studies have focused on explaining the cellular mechanisms that lead to the formation of dental structures (for example, dentin, the periodontal ligament, dental pulp, or enamel), which has contributed to this knowledge, leading to the design of novel biomaterials destined to stimulate regeneration in dental and nondental tissues. Natural biomaterials are constituents of the ECM or represent macromolecular properties that are similar to the ECM. These can be classified into two main categories, protein-based and natural biomaterials based on polysaccharides. Collagen, fibrin, and elastin are the most explored natural protein-based biomaterials [13, 37]. Polysaccharide-based biomaterials are natural polymers consisting of sugar monomers. Chitosan, alginate, glycosaminoglycans (GAGs), and hyaluronic acid are examples [38]. Most natural biomaterials present favorable biocompatibility and immunogenicity and low cost [39], making them attractive for their application in tissue engineering in the field of endodontics. One of the most widely studied biomaterials in the dental field is collagen due to its role in ECM in dental pulp and dentin, its function as a natural hemostatic agent [40], its hydrophilicity, biocompatibility, biodegradability, and its low immunogenicity and cytotoxicity [41]. In this sense, biomaterials based on type I collagen (Col-I) have been developed to generate tissues, such as dental pulp [42], dentin [43], and guided bone regeneration treatments [44]. This shows that collagen-based biomaterials are an important element in dental research; however, the difficulties encountered in regenerative endodontics of root canals indicate irregular biodegradation and the generation of connective tissue instead of dentin in vivo. Another widely investigated polysaccharide is chitosan (CHS), which is purified mainly from chitin. Chemically, CHS is a polymeric material comprised of N-acetylglucosamine and glucosamine copolymer units [45]. CHS has also been reported to be a direct pulp cap with the purpose of initiating the formation of reparative dentin to help protect the pulp, favoring the differentiation of DPSCs into odontoblast-like cells [46]. The use of CHS in conjunction with DPSCs has been studied to induce bone regeneration and for the treatment of chronic periodontitis. [47]. For example, [PERSON] and [PERSON] (2018) [48] used CHS with DPSCs to evaluate the potential for bone formation around dental implants. They noted that this method helped bone maturation around the implant, suggesting its potential use in bone regeneration [48]. Fibrin is a fibrillar biopolymer and the main component of the blood coagulation matrix. This protein has been reported as a vehicle for the release of dental stem cells since it facilitates their union, growth, and differentiation [49, 50]. Its advantages include excellent biocompatibility, bioresorbability, hemostatic properties, nontoxicity of degradation products, and the short-term generation of an ECM produced by stem cells incorporated into the biomaterial. Although there is increasing development of biomaterials with natural polymers due to their similarity with ECM, the biochemical characteristics of fibrin make it suitable as a platform for autologous cell release. For a better understanding of the composition, structure, biochemical characteristics and mechanical properties of fibrin, the reader is referred to excellent reviews about this biomaterial [51; 52; 53]. One of the interesting features of fibrin is that it can form a three-dimensional network of elastic fibers which can promote biological interactions during the regeneration of target tissues. [49]. To date, two types of fibrin-based products have been used: glue and hydrogels.