Fiorilli Sonia, Pagani Mattia, Boggio Elena, Gigliotti Casimiro Luca, Dianzani Chiara, Gauthier Rémy, Pontremoli Carlotta, Montalbano Giorgia, Dianzani Umberto, Vitale-Brovarone Chiara
Department of Applied Science and Technology, Politecnico di Torino, Corso Duca degli Abruzzi 24, 10129 Torino, Italy.
NOVAICOS s.r.l.s, Via Amico Canobio 4/6, 28100 Novara, Italy.
Nanomaterials (Basel). 2021 Jan 27;11(2):321. doi: 10.3390/nano11020321.
Osteoporotic bone fractures represent a critical clinical issue and require personalized and specific treatments in order to stimulate compromised bone tissue regeneration. In this clinical context, the development of smart nano-biomaterials able to synergistically combine chemical and biological cues to exert specific therapeutic effects (i.e., pro-osteogenic, anti-clastogenic) can allow the design of effective medical solutions. With this aim, in this work, strontium-containing mesoporous bioactive glasses (MBGs) were bio-functionalized with ICOS-Fc, a molecule able to reversibly inhibit osteoclast activity by binding the respective ligand (ICOS-L) and to induce a decrease of bone resorption activity. N adsorption analysis and FT-IR spectroscopy were used to assess the successful grafting of ICOS-Fc on the surface of Sr-containing MBGs, which were also proved to retain the peculiar ability to release osteogenic strontium ions and an excellent bioactivity after functionalization. An ELISA-like assay allowed to confirm that grafted ICOS-Fc molecules were able to bind ICOS-L (the ICOS binding ligand) and to investigate the stability of the amide binding to hydrolysis in aqueous environment up to 21 days. In analogy to the free form of the molecule, the inhibitory effect of grafted ICOS-Fc on cell migratory activity was demonstrated by using ICOSL positive cell lines and the ability to inhibit osteoclast differentiation and function was confirmed by monitoring the differentiation of monocyte-derived osteoclasts (MDOCs), which revealed a strong inhibitory effect, also proven by the downregulation of osteoclast differentiation genes. The obtained results showed that the combination of ICOS-Fc with the intrinsic properties of Sr-containing MBGs represents a very promising approach to design personalized solutions for patients affected by compromised bone remodeling (i.e., osteoporosis fractures).
骨质疏松性骨折是一个关键的临床问题，需要个性化的特定治疗方法来刺激受损骨组织的再生。在这种临床背景下，开发能够协同结合化学和生物学信号以发挥特定治疗效果（即成骨、抗破骨）的智能纳米生物材料，可以设计出有效的医疗解决方案。为此，在本研究中，含锶介孔生物活性玻璃（MBG）用ICOS-Fc进行了生物功能化，ICOS-Fc是一种能够通过结合相应配体（ICOS-L）可逆地抑制破骨细胞活性并降低骨吸收活性的分子。采用N吸附分析和傅里叶变换红外光谱（FT-IR）来评估ICOS-Fc在含Sr的MBG表面的成功接枝，结果还证明功能化后的材料保留了释放成骨锶离子的特殊能力以及优异的生物活性。一种类似酶联免疫吸附测定（ELISA）的方法证实了接枝的ICOS-Fc分子能够结合ICOS-L（ICOS结合配体），并研究了酰胺键在水环境中直至21天的水解稳定性。与该分子的游离形式类似，通过使用ICOSL阳性细胞系证明了接枝的ICOS-Fc对细胞迁移活性的抑制作用，并通过监测单核细胞来源的破骨细胞（MDOC）的分化证实了其抑制破骨细胞分化和功能的能力，破骨细胞分化基因的下调也证明了这种强大的抑制作用。所得结果表明，ICOS-Fc与含Sr的MBG的固有特性相结合，是为受骨重塑受损（即骨质疏松性骨折）影响的患者设计个性化解决方案的一种非常有前景的方法。
