title: 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.
authors.affiliation: Group of Cell Therapy and Tissue Engineering, Research Institute on Health Sciences (IUNICS), University of the Balearic Islands, Ctra. Valldemossa km 7.5, 07122, Palma de Mallorca, Spain.
authors.forename: Alba
authors.initials: A
authors.lastname: Córdoba
authors.forename: María
authors.initials: M
authors.lastname: Satué
authors.forename: Manuel
authors.initials: M
authors.lastname: Gómez-Florit
authors.forename: Margarita
authors.initials: M
authors.lastname: Hierro-Oliva
authors.forename: Christiane
authors.initials: C
authors.lastname: Petzold
authors.forename: Staale P
authors.initials: SP
authors.lastname: Lyngstadaas
authors.forename: María Luisa
authors.initials: ML
authors.lastname: González-Martín
authors.forename: Marta
authors.initials: M
authors.lastname: Monjo
authors.forename: Joana M
authors.initials: JM
authors.lastname: Ramis
mesh_terms: D000469:Alkaline Phosphatase / Q000378:metabolism; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001672:Biocompatible Materials / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D048430:Cell Shape / Q000187:drug effects; D002478:Cells, Cultured; D005347:Fibroblasts / Q000166:cytology; D005355:Fibrosis; D005419:Flavonoids / Q000737:chemistry / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects; D005881:Gingiva / Q000166:cytology; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008856:Microscopy, Fluorescence; D010012:Osteogenesis / Q000187:drug effects*; D056951:Photoelectron Spectroscopy; D017550:Spectroscopy, Fourier Transform Infrared; D014025:Titanium / Q000494:pharmacology; D017155:Wettability
chemical_list: D000893:Anti-Inflammatory Agents; D001672:Biocompatible Materials; D005419:Flavonoids; D014025:Titanium; D007770:L-Lactate Dehydrogenase; D000469:Alkaline Phosphatase; D002118:Calcium
keywords: bioactivity; biomaterials; flavonoids; surface functionalization; titanium