# Nanomaterials in Craniofacial Tissue Regeneration: A Review
## 3 Clinical Applications
### Bone Regeneration for Dental Implants and Mandibular Defects  
With the wide use of dental implants as an option to replace missing teeth, bone regeneration is becoming an integral part of oral rehabilitation. Prior to the placement of a dental implant, an adequate amount of alveolar bone is essential. Similarly, segmental bone defects in the oral maxillofacial region--a condition that arises through trauma, infection, tumor resection or osteoradionecrosis--can also be addressed, given a sufficient amount of alveolar process. To facilitate such repairs, autogenous bone grafts (autografts) have been the gold standard in bone regeneration [59]. While serving as a scaffold for bone formation, autografts also contain bone-forming cells and bioactive substances that induce new bone formation. However, several disadvantages are associated with autograft use, including endogenous donor site morbidity and limited availability. A potential need for general anesthesia motivates clinicians and researchers to develop substitute bone graft materials that have excellent bioactivity and osteoconductivity [60]. The success of new bone regeneration can be greatly improved when the osteoconductive scaffold in use contains macropores (>200 \(\upmu\)m). Such a structure allows for adequate flow and distribution of biofactors such as oxygen and nutrients, rapid vascularization, osteoblast proliferation and differentiation, bone remodeling, and osseointegration throughout the healing process [61; 62]. New bone deposition can be furthered by enhancing these scaffolds with bactericidal properties, which ultimately control infection post-treatment [62]. This section will explore the feasibility of using various nanomaterials in dental implants and mandibular bone defects, such as nHA composite scaffolds, nanomodified mineral trioxide aggregate, and graphene. Previously, a multitude of synthetic bone graft substitutes have been developed to function as scaffolds, including hydroxyapatite (HA), biphasic calcium phosphate ceramics, and tricalcium phosphate. The field of nanotechnology can be applied to scaffolds such as HA to create nHA, which was shown to enhance bone regeneration and to accelerate healing after sinus augmentation [60]. In fact, nHA displayed similar effects in bone regeneration compared to freeze dried bone allografts in a rabbit model [63]. In addition, nHA used in the augmentation of extraction sockets was shown to reduce the degree of gingival invaginations [64]. While nHA was promising for bone regeneration, there were some drawbacks, such as its brittleness and low mechanical properties. These limitations consequently prevented nHA from bearing larger loads or forces. However, using nHA in combination with other high molecular weight polymers could improve its mechanical strength as well as its biocompatibility. nHA was combined with other materials, including collagen, PLA, PLGA, polyamide, coralline, chitosan, and PCL [7]. For example, a nanostructured carbonate hydroxyapatite/calcium alginate (CHA) microsphere was developed by substituting the phosphate group (PO\({}_{4}\)) with a carbonate group (CO\({}_{3}\)). The microspheres produced at low temperatures showed lower crystallinity and higher solubility, which favored an earlier resorption time and improved bone regeneration [65; 66]. When combined with collagen, nHA/collagen composite scaffolds aimed to mimic the architecture of native bone. In a study by [PERSON] et al., they showed that as the ratio of collagen to nHA increased, the mechanical property of the scaffold decreased but could increase the rate of bone tissue formation [67]. Another group, [PERSON] et al., studied the effects of nHA/collagen/PLA composite scaffolds with human alveolar BMSCs and determined that they could be used to successfully correct mandibular bone defects, while [PERSON] et al. improved the osteogenesis activity of nHA/recombinant human-like collagen/PLA scaffolds with the addition of a polydopamine-assisted BMP-2-derived peptide [59; 68].