Flavonoid-Modified Surfaces: Multifunctional Bioactive Biomaterials with Osteopromotive, Anti-Inflammatory, and Anti-Fibrotic Potential
Flavonoid-Modified Surfaces: Multifunctional Bioactive Biomaterials with Osteopromotive, Anti-Inflammatory, and Anti-Fibrotic Potential
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DOI：
10.1002/adhm.201400587
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发表时间：
2015-03-11
影响因子：
10
通讯作者：
Ramis, Joana M.
中科院分区：
文献类型：
--
作者：
Cordoba, Alba;Satue, Maria;Ramis, Joana M.
黄酮类化合物是天然来源的小多酚分子，具有抗氧化、抗炎和抗菌特性。在这里，提出了一种生物活性表面的基础上共价固定的类黄酮紫杉叶素和槲皮苷钛基板上，使用（3-氨丙基）三乙氧基硅烷（APTES）作为偶联剂。FTIR和XPS测量证实了类黄酮接枝到表面。使用2-氨基乙基二苯基硼酸酯（DPBA，类黄酮特异性染料），改性的表面通过荧光显微镜成像。类黄酮修饰的表面的生物活性在体外用人脐带来源的间充质干细胞（hUC-MSC）和人牙龈成纤维细胞（HGFs）进行评估，并与通过滴铸制备的简单类黄酮涂层的生物活性进行比较。类黄酮修饰的表面显示出对HGF的抗炎和抗纤维化潜力。此外，类黄酮共价功能化的钛表面促进hUC-MSCs向成骨细胞的分化，增强成骨标志物的表达，增加碱性磷酸酶活性和钙沉积;而滴铸表面则没有。这些发现可能对骨植入物等先进植入式医疗器械的开发产生重大影响。鉴于类黄酮化合物的广泛生物活性，这些表面准备用于其他生物医学应用，例如，作为用于心血管或癌症治疗的支架表面或肿瘤靶向功能化纳米颗粒。
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 osteoblastsenhancing 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.