# Bioactivity and Delivery Strategies of Phytochemical Compounds in Bone Tissue Regeneration
## 5 Phytochemical-Delivery Vehicles in Bone Tissue Regeneration
### Ceramics  
Synthetic ceramic materials are inorganic material favorably used in dentistry that proved excellent mechanical properties and osteo-conduciveness owing to their good biocompatibility, reproducibility, non-immunogenicity [117; 118]. Ceramic nanocomposites in the form of particles or nanofibers could mimic the hierarchical arrangement of native bone mineral phase, providing a functional scaffold for cell adhesion [119; 120; 121; 122], but are  
\begin{table}
\begin{tabular}{c c c} \hline \hline
**Pytochemical** & **Signaling Pathway** & **Reference** \\ \hline Curcumin & NF-kB pathways, & [75; 89; 90] \\ \multirow{2}{*}{EGCG} & Redox-sensitive signaling pathways & [82] \\  & COX2/HIF1 assigning & [83; 84; 108] \\  & ERK1-2/MAPKs signaling & [83; 84; 108] \\ \multirow{2}{*}{Resveratrol} & Redox-sensitive signaling pathways & \\  & Stir/RUNX2 signaling & [89; 90; 109] \\  & MAPKs pathways & \\ \multirow{2}{*}{Incaritin} & NFATc signaling & [87] \\  & _Glutathione Pathway (GSH)_ & [88] \\ \multirow{2}{*}{Myricetin} & SMAD/BMP signaling & [97] \\  & Wnt/\(\beta\)-catenin signaling & [101] \\ \multirow{2}{*}{Vanillic acid} & ERs pathways & [102; 103] \\ \multirow{2}{*}{Rutin} & ERs pathways & [102; 103] \\ \hline \hline \end{tabular}
\end{table}
Table 1: Summary of phytochemical signaling pathways for bone regeneration.  
not able to prevent the cause of bone resorption, to control specific anti-osteoclasteogenic actions, or to counteract the damage related to oxidative stress. To overcome these disadvantages, polyphenols are widely used to enhance periodontal regeneration or to re-mineralize bone tissue, due to their antioxidant, free-radical scavenging, and antimicrobial properties [123; 124; 125]. The preparation of these composites is often optimized to form nanopores (pore diameter < 0.1 \(\upmu\)m) to increase the specific surface area of the scaffolds, allowing for better drug loading and higher bioactivity [125]. For example, [PERSON] et al. patented a polyphenol-based collagen gel with granular ceramic fillers to fill the peri-implant bone defects. Such material, characterized by strong mechanical scaffolding properties, combines the pro-osteogenic action of collagen with the anti-inflammatory, antioxidant, and anti-osteoclasteogenic activity of a polyphenic mixture extracted from the pomace of the _Croatina_ grape variety [126]. In vitro and in vivo results demonstrated that both the control of inflammation and oxidative stress and the enhancement of early bone matrix deposition are necessary in the case of oral disease. [PERSON] et al. produced a silica-based bioactive glass coupled with gallic acid and polyphenols extracted from red grape skins and green tea leaves. These modified bioactive glasses showed enhanced free radical scavenging activity [127]. [PERSON] et al. proposed a simple protocol to functionalize porous calcium phosphate ceramics (PCPC) using dietetic tea polyphenols (TP). TP molecules modulated the nucleation and crystallization of calcium phosphate nanorods and promoted bone mesenchymal stem cell (BMSC) proliferation and differentiation, increasing BMP2, ErK/MAPK, and JNK/MAPK levels and cell mineralization capacity [128].  
Figure 2: Schematic representation of the main phyto-bioactive nano delivery systems involved in bone regeneration.