PDF(Pubmed)
Abstract：
Conventional bone scaffolds, which are mainly ascribed to highly active osteoclasts and an inflammatory microenvironment with high levels of reactive oxygen species and pro-inflammatory factors, barely satisfy osteoporotic defect repair. Herein, multifunctional self-assembled supramolecular fiber hydrogels (Ce-Aln gel) consisting of alendronate (Aln) and cerium (Ce) ions were constructed for osteoporotic bone defect repair. Based on the reversible interaction and polyvalent cerium ions, the Ce-Aln gel, which was mainly composed of ionic coordination and hydrogen bonds, displayed good injectability and autocatalytic amplification of the antioxidant effect. In vitro studies showed that the Ce-Aln gel effectively maintained the biological function of osteoblasts by regulating redox homeostasis and improved the inflammatory microenvironment to enhance the inhibitory effect on osteoclasts. Ribonucleic acid (RNA) sequencing further revealed significant downregulation of various metabolic pathways, including apoptosis signaling, hypoxia metabolism and tumor necrosis factor-alpha (TNF-α) signaling via the nuclear factor kappa-B pathway after treatment with the Ce-Aln gel. In vivo experiments showed that the clinical drug-based Ce-Aln gel effectively promoted the tissue repair of osteoporotic bone defects by improving inflammation and inhibiting osteoclast formation at the defect. Notably, in vivo systemic osteoporosis was significantly ameliorated, highlighting the strong potential of clinical translation for precise therapy of bone defects.
摘要：
传统的骨支架，这主要归因于高活性破骨细胞和具有高水平活性氧和促炎因子的炎症微环境，勉强满足骨质疏松缺损修复。在这里，构建了由阿仑膦酸盐（Aln）和铈（Ce）离子组成的多功能自组装超分子纤维水凝胶（Ce-Alngel），用于骨质疏松性骨缺损的修复。基于与多价铈离子的可逆相互作用,Ce-Aln凝胶，主要由离子配位和氢键组成，表现出良好的可注射性和抗氧化作用的自催化放大。体外研究表明，Ce-Aln凝胶通过调节氧化还原稳态，有效维持成骨细胞的生物学功能，改善炎症微环境，增强对破骨细胞的抑制作用。核糖核酸（RNA）测序进一步揭示了各种代谢途径的显着下调，包括凋亡信号，Ce-Aln凝胶治疗后，缺氧代谢和肿瘤坏死因子-α（TNF-α）信号通过核因子κB途径。体内实验表明，临床药物Ce-Aln凝胶通过改善炎症反应和抑制缺损处破骨细胞的形成，有效促进骨质疏松性骨缺损的组织修复。值得注意的是,体内全身性骨质疏松症显着改善，突出了临床转化对精确治疗骨缺损的强大潜力。
