Flavonoid‐Modified Surfaces: Multifunctional Bioactive Biomaterials with Osteopromotive, Anti‐Inflammatory, and Anti‐Fibrotic Potential

Abstract

Flavonoids are small polyphenolic molecules of natural origin with antioxidant, anti-inflammatory, and antibacterial properties. Here, a bioactive surface based on the covalent immobilization of flavonoids taxifolin and quercitrin on titanium substrates is presented, using (3-aminopropyl)triethoxysilane (APTES) as coupling agent. FTIR and XPS measurements confirm the grafting of the flavonoids to the surfaces. Using 2-aminoethyl diphenylborinate (DPBA, a flavonoid-specific dye), the modified surfaces are imaged by fluorescence microscopy. The bioactivity of the flavonoid-modified surfaces is evaluated in vitro with human umbilical cord derived mesenchymal stem cells (hUC-MSCs) and human gingival fibroblasts (HGFs) and compared to that of simple flavonoid coatings prepared by drop casting. Flavonoid-modified surfaces show anti-inflammatory and anti-fibrotic potential on HGF. In addition, Ti surfaces covalently functionalized with flavonoids promote the differentiation of hUC-MSCs to osteoblasts--enhancing the expression of osteogenic markers, increasing alkaline phosphatase activity and calcium deposition; while drop-casted surfaces do not. These findings could have a high impact in the development of advanced implantable medical devices like bone implants. Given the broad range of bioactivities of flavonoid compounds, these surfaces are ready to be explored for other biomedical applications, e.g., as stent surface or tumor-targeted functionalized nanoparticles for cardiovascular or cancer therapies.

Bioinspired Quercitrin Nanocoatings: A Fluorescence-Based Method for Their Surface Quantification, and Their Effect on Stem Cell Adhesion and Differentiation to the Osteoblastic Lineage

“…The surfaces showed promising bone-stimulating, anti-inflammatory, and antifibrotic effects in vitro, on human mesenchymal stem cells (hMSCs) derived from umbilical cord, and human gingival fibroblasts cultured on the surfaces. 11 Furthermore, the biological effects were similar to those observed previously on cells treated with these flavonoid compounds in solution, 12−14 proving that the covalent immobilization of flavonoids to a surface through its ketone group does not impair its bioactive behavior. These multifunctional bioactive flavonoid-modified surfaces could have a potential application in bone implant surfaces to decrease the risk of implant failure, since the main causes of bone implant failure are related either to a fibrous tissue integration around the implant, which causes an encapsulation of the implant, or to the occurrence of inflammatory procedures or bacterial infections such as peri-implantitis.…”

“…Then the coins were dried under a N 2 flow and immediately aminosilanized with 2% APTES in dry toluene for 24 h. To obtain QR samples (Figure 1), the aminosilanized surfaces were chemically functionalized with quercitrin by immersion in a quercitrin hydrate 1 mM aqueous solution (250 μL/ coin) at pH 5.5 for 1 h, as previously described. 11 In this step, the reaction of the ketone moiety of the flavonoid with the terminal amine group of the silane at mildly acidic pH gave an imine (CN) bond between the APTES cross-linker and the flavonoid. To optimize the quercitrin coating, the use of NaCNBH 3 to selectively reduce the imine bond between the flavonoid and the silane to a single C−N bond was evaluated.…”

“…22 In our previous work, we observed that surfaces functionalized with flavonoids were more hydrophilic than control Ti substrates. 11 On the other hand, Choi et al 23 confirmed the need for specific interactions between the catechol moieties and the cells when comparing surfaces with similar surface wettabilities, and proposed an adhesion mechanism dependent on the specific linkage between catechol and thiolated biological molecules such as proteins. We hypothesized here that quercitrin coatings could enhance a rapid cell adhesion due to the presence of cathecol groups on the surface.…”

The role of kaempferol-induced autophagy on differentiation and mineralization of osteoblastic MC3T3-E1 cells

“…Flavonoids are naturally occurring compounds found in food in the human diet [6]. They are also used in medicine [6].…”

“…They are also used in medicine [6]. Flavonoids are known to be very effective in the prevention of cancer and cardiovascular, neurodegenerative [24] and metabolic bone diseases [25].…”