# Bioactivity and Delivery Strategies of Phytochemical Compounds in Bone Tissue Regeneration
## 5 Phytochemical-Delivery Vehicles in Bone Tissue Regeneration
### Nanoparticles  
The therapeutic efficacy of natural bioactive molecules can be improved by nanotechnological approaches. The design of drug delivery systems with pre-determined physico-chemical properties permits an increase of phytochemical bioavailability and reduces their toxic side effects [53]. For example, positive surface charges could facilitate the transport of nanoparticles through small intestinal epithelial cells improving the oral bioavailability, while the introduction of polyethylene glycol chains limits opsonization prolonging circulation times [143; 144; 145]. Moreover, the modulation of structure-property  
Figure 4: Photographs of animal modeling in vivo. Defects on the cranial bone (**a**,**b**) materials implanted. Courtesy of: [PERSON], [PERSON], [PERSON], [PERSON], [PERSON] Surface modification of strontium-doped porous bioactive ceramic scaffolds via poly(DOPA) coating and immobilizing silk fibroin for excellent angiogenic and osteogenic properties. Biomater Sci. April 2016;4(4):678-88. doi: 10.1039/c5 bm00482a. Epub 12 February 2016. PMID: 26870855.  
Figure 3: Image (**1**) represents cells cultured with different scaffolds. Image (**2**) shows scaffolds alizarin red staining on day 4 (**a**–**c**), day 7 (**d**–**f**), day 10 (**g**–**i**), day 14 (**j**–**l**); SCPP (**a**,**d**,**g**,**j**), D-SCPP (**b**,**e**,**h**,**k**), SCPP/D/SF (**c**,**f**,**i**,**l**), respectively. Green arrows: calcium nodules. Courtesy of: [PERSON], [PERSON], [PERSON], [PERSON], [PERSON] Surface modification of strontium-doped porous bioactive ceramic scaffolds via poly(DOPA) coating and immobilizing silk fibroin for excellent angiogenic and osteogenic properties. Biomater Sci. April 2016;4(4):678-88. doi: 10.1039/c5 bm00482a. Epub 12 February 2016. PMID: 26870855.  
relationships (i.e., size, geometry or shape, material composition, etc.) of nanoparticles can influence the transport mechanism, facilitating their internalization into the target cells.  
[PERSON] et al. produced tea polyphenol-modified calcium phosphate nanoparticles (TP-CaP) able to enhance remineralization of preformed enamel lesions on bovine incisors. Moreover, the released tea polyphenols inhibited bacterial growth and enzyme activities [146]. [PERSON] produced gold nanoparticles (Au-NPs) formed using Anogeissus latifolia (A. latifolia) phytochemicals. Such nano-vehicles showed great osteoinductive potential and analgesic properties and were characterized by exceptional blood compatibility and cytocompatibility [147]. [PERSON] et al. synthesized polyphenol-based mucoadhesive polymeric nanoparticles (GSE-NP) able to protect endothelial progenitor cells (EPCs) from oxidative stress. These vehicles demonstrated strong antioxidant capacity thanks to their high content in total polyphenols [148]. [PERSON] et al. synthesized nanoparticles of PCL and Pluronic(r) F-68, loaded with curcumin. These nanoparticles were able to reduce cell proliferation without affecting cell migration and adhesion, and decrease the oxidative stress induced by hydrogen peroxide exhibiting a cytoprotective effect [149]. Finally, [PERSON] and [PERSON] used chitosan to prepare Naringin-loaded chitosan nanoparticles (NCN). The NCN had strong anti-inflammatory, anti-coagulant, antioxidant, and anti-cancerous effects. Furthermore, these nanoparticles promoted osteoblast differentiation, so they could be considered an efficient model for bone tissue regeneration [150]. All described delivery systems are summarized in Table 2.