# Nanomaterials in Craniofacial Tissue Regeneration: A Review
## 3 Clinical Applications
### Cartilage Tissue Regeneration (Temporomandibular Joint)  
Up to 70% of temporomandibular joint disorder (TMD) cases are associated with displacement of the temporomandibular joint (TMJ) disc [44]. The difficulty in restoring the damaged TMJ disc lies in its limited intrinsic regenerative capacity. Current treatments of a severely damaged or displaced TMJ disc often results in a disectomy when the TMJ disc becomes too difficult to repair or to reposition [45; 46]. Research in TMJ disc tissue engineering has explored methods based on scaffolds, cell sources, and biological/biomechanical stimuli [44; 47]. Potential applications for TMJ disc regeneration include the incorporation of nanomaterial scaffolds (nanosurfaces, nanofibers, and nanocomposites) used for cartilage tissue engineering [48; 49; 50].  
Nanosurface-type scaffolds have geometrically defined nanopatterns on their surfaces [50]. [PERSON] et al. modified polyurethane and PCL surfaces by casting these surfaces over a spiky titanium surface, which resulted in an increase of chondrocyte numbers, intracellular chondrocyte protein production, and chondrocyte collagen secretion [51]. Surface modifications were also performed by [PERSON] et al., who modified PLGA scaffolds with sodium hydroxide, resulting in an increase of chondrocyte numbers, and intracellular/extracellular protein contents [52].  
Nanofibrous-type scaffolds consist of proteins such as collagen and elastin and can be created through electrospinning or thermally induced phase separation [53]. [PERSON] et al. found that a nanofibrous osteochondral scaffold could selectively differentiate human adipose-derived stromal cells resulting in the regeneration of osteochondral tissue [54]. In areas of increased insulin and \(\beta\)-glycerophosphate, they found that chondrogenic differentiation and mineralization increased, respectively [54]. Nanofibrous scaffolds were also made from poly(\(\beta\)-caprolactone)-blockpoly(L-lactide) copolymers and were found to increase collagen type II expression in chondrocytes [50]. Electrospun PLA nanofibers with surface carboxylate groups were created by [PERSON] and [PERSON] and were found to enhance the viability, proliferation, and differentiation of rabbit articular chondrocytes [55]. Similarly, electrospun poly(_z_-caprolactone) matrices with a nanofiber network also showed an increase in osteochondral regeneration [56].  
Nanocomposite-based scaffolds have been shown to be useful in this field as well. Electrospun PLA with hydroxyapatite nanoparticles have been found to increase chondrogenic differentiation of mesenchymal stem cells, while gold nanoparticles incorporated into porcine collagen hydrogels increased the mechanical properties of the hydrogel and increased chondrocyte proliferation [50]. Similarly, PLGA/titanium dioxide composite scaffolds with modified surfaces were created by treatment with various concentrations of sodium hydroxide and resulted in an increase in osteoblast and chondrocyte adhesion [57].  
Other studies, such as the one by [PERSON] et al., assessed the biocompatibility of single-wall carbon nanotubes for articular cartilage tissue engineering and found that these nanotubes promoted the expression of a chondrogenic ECM [58].  
TMJ disc cartilage tissue engineering is a relatively new and underexplored field [48]. The use of nanomaterials in cartilage tissue engineering has improved the interaction between cells and scaffolds to allow for greater tissue growth, cell differentiation, adhesion, and synthesis of a cartilaginous ECM [50]. Many cartilage tissue engineering studies, however, focus on the articular cartilage of the knee joint, and the data supporting TMJ disc regeneration is still lacking [7]. As research in this field further develops, it is expected that research involving the use of nanomaterials will play a greater role in addressing TMJ cartilage tissue engineering through engineered TMJ cartilage constructs that functionally resemble its natural cartilage tissue counterpart.