# Nanomaterials in Bone Regeneration
## 4 Nanoparticles
### Gold Nanoparticles  
Gold nanoparticles (Au-NPs) are the most interesting among the noble metal nanoparticles. The unique properties of Au-NPs, such as good biocompatibility, easy synthesis, and surface ligand functionalization, make them promising nanomaterials in biomedical applications like drug delivery, biological imaging, diagnosis, and treatment of diseases [94].  
In recent years, Au-NPs have gained attention as next-generation osteogenic agents for bone regeneration [95]. [PERSON] et al. reported that Au-NPs have regulatory effects on macrophages and osteogenesis of stem cells and osteoblasts. This effect depends on different particle sizes, concentrations, and surface modifications. Au-NPs promoted osteogenic differentiation in a size-dependent manner. Three sizes of nanoparticles (5 nm, 13 nm, and 45 nm) were used for the experiment. Particles sized 13 nm and 45 nm showed the highest potency to promote osteogenesis on periodontal ligament progenitor cells and expressed _OPN_ mRNA. On the other hand, 5 nm Au-NPs significantly reduced ALP activity, expression of osteogenic genes, and mineralized nodule formation [96]. These results support the finding that smaller nanoparticles do not produce enough free energy and therefore form clusters to receive the driving force to enter the cells [97].  
Au-NPs promote the osteogenesis of MSCs through different signaling pathways. [PERSON] et al. studied osteogenic differentiation of stem cells through the Wnt/\(\beta\)-catenin pathway. Osteogenesis of bone-derived MSCs and AD-MSCs was promoted by activating the p38 MAPK signaling pathway and the Wnt/\(\beta\)-catenin signaling pathway, respectively [98]. The osteogenic differentiation of bone marrow-derived MSCs (BM-MSCs) was stimulated by citrate-reduced Au-NPs through the mitogen-activated protein kinase signaling pathway. An Au-NPs-hydrogel complex increased the osteogenic differentiation of fibroblasts through the BMP signaling [99].  
In a study by [PERSON] et al., Au-NPs coated with synthetic oligonucleotides showed good biocompatibility, stability, and efficient uptake by the cells. Au-NPs tailored with oligonucleotides facilitate the targeted detection of specific mRNA and can be used to isolate specific skeletal cell populations from the mixture of bone marrow stromal cells. Transmission electron microscope analysis revealed that the Au-NPs interacted with cytoplasmic proteins of specific signaling pathways, upregulated osteogenic genes, and downregulated adipogenic genes [100].  
[PERSON] et al. integrated Au-NPs into the bone scaffolds. This enhancement helps bone regeneration by achieving properties such as osteoconductivity, osteoinduction, appropriate resorption rate, and mechanical strength. Au-NPs synthesized through immobilization of _Bacillus licheniformis_ crude enzyme were studied on murine preosteoblast cell line (MC3T3) and BM-MSCs. Good osteocompatibility, anti-oxidant, osteopromotive and hemocompatibility properties, and increased bone mineralization were observed [95]. [PERSON] et al. prepared nanomaterials by incorporating hydrogel with Au-NPs by photo-crosslinking. The addition of Au-NPs promoted high ALP activity, cell proliferation, cell viability, and osteogenic differentiation of adipose-derived stromal cells [101].