# Nanomaterials in Craniofacial Tissue Regeneration: A Review
## 3 Clinical Applications
### Vascular Tissue Regeneration (Endodontics)  
#### 3.2.1 Dental Pulp  
Underneath the exterior hard tissues of a tooth is an unmineralized soft tissue core called dental pulp. The pulp is composed of connective tissue, immune cells, odontoblasts, nerve fibers, and blood vessels [15; 34]. This unique composition enables the pulp to produce and maintain dentin, and provides immunity, nutrition, tooth vitality, and sensation. However, the pulp is prone to caries, trauma, and infections, which lead to pulpitis--inflammation of the pulp, which is generally painful and irreversible. This ultimately results in pulp necrosis, which ceases tooth functionality and vitality [15; 16; 35]. There is an ongoing challenge in overcoming these pulpal injuries; to date, there is little to no success in the restoration of the pulp tissue once diseased or damaged. A major challenge that hinders the success of restoring pulp tissue is due to difficulties in revascularization of the tissue caused by the unique and miniscule source of blood flow at the apex of the tooth root [17]. The lack of a -vasculature system leads to a loss of nutrients diffusion. As a result, patients will often have to undergo a root canal procedure to salvage the remaining hard tissues of the tooth, which leaves the tooth in a weakened, nonvital state [15; 17]. The crucial role of vascular tissue, in addition to the insufficient repair protocols for dental pulp, highlights the need for research in alternative methods for treating dental pulp injury. This section aims to examine recent studies exploring the uses of nanomaterials as a potential alternative solution to address pulp injuries. There is increasing evidence on the feasibility of using nanomaterials in tissue engineering in recent literature. In general, using nanomaterials as a scaffold offers improved controlled allocation of active molecules and, thus, better promotion of niche formations, mirroring the complexity found in soft tissues [35]. Polymeric nanomaterials, more specifically, are explored for drug delivery, tissue engineering scaffolds, the creation of medical devices, and for diagnosis due to their advantages, as previously discussed in Section 2.2. [36]. In a study by [PERSON] et al., they addressed pulp injuries by exploring pulp tissue regeneration via a biomaterial scaffold composed of self-assembling peptide nanofibers [15]. The small 6-nm-diameter property of these nanofibers enabled the synthetic scaffold to mimic a structural mesh that was similar to a naturally-occurring ECM, which was optimal for cellular activities such as cell-cell and cell-matrix interactions. Additionally, the nanofiber material was also able to encapsulate dental pulp stem cells (DPSCs) and the various growth factors needed to foster angiogenesis (the formation of new blood vessels) and cell growth, differentiation, and morphogenesis, such as the fibroblast growth factor 2 (FGF2), transforming growth factor \(\beta\)1, and vascular endothelial growth factor (VEGF) [15]. The encapsulation of such growth factors allows for the sustained and unmonitored, yet controlled release of these factors over a period of time. [PERSON] et al. were able to induce in vivo angiogenesis in artificial teeth implanted in mice using these self-assembling peptide nanofibers. To investigate the potential of graphene in tissue engineering, [PERSON] et al. compared the effect of graphene to glass. They found that graphene could induce greater mineralization, and osteogenic, but not odontoblastic, differentiation of DPSCs [37]. Similarly, the concept of using polymeric nanomaterials to encapsulate drugs, particles, cells, and/or growth factors to facilitate tissue engineering was reinforced in other studies, such as the ones by [PERSON] et al. and [PERSON] et al. [16; 17]. However, while both studies also took advantage of polymeric nanofibers to simulate natural ECM to promote pulp formation and vascularization, different types of polymers were used to form the nanofibers; [PERSON] et al.