Han Zhihui, Gao Xiang, Wang Yuanjie, Huang Cheng, Song Hao, Cheng Shuning, Yang Xiaoyuan, Cui Xiaoliang, Wu Jie, Wei Kailu, Cheng Liang
Institute of Functional Nano & Soft Materials (FUNSOM), Collaborative Innovation Center of Suzhou Nano Science and Technology, Soochow University, Suzhou 215123, China.
Department of Orthopedics, The Second Affiliated Hospital of Soochow University, Suzhou 215004, China.
Natl Sci Rev. 2024 Jun 20;11(7):nwae209. doi: 10.1093/nsr/nwae209. eCollection 2024 Jul.
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. 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. 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, systemic osteoporosis was significantly ameliorated, highlighting the strong potential of clinical translation for precise therapy of bone defects.
传统的骨支架主要归因于高活性破骨细胞以及具有高水平活性氧和促炎因子的炎症微环境，几乎无法满足骨质疏松性骨缺损的修复需求。在此，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-Aln凝胶）用于骨质疏松性骨缺损修复。基于可逆相互作用和多价铈离子，主要由离子配位和氢键组成的Ce-Aln凝胶表现出良好的可注射性和抗氧化作用的自催化放大。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，并改善炎症微环境以增强对破骨细胞的抑制作用。核糖核酸（RNA）测序进一步揭示，在用Ce-Aln凝胶处理后，包括凋亡信号传导、缺氧代谢和通过核因子κB途径的肿瘤坏死因子-α（TNF-α）信号传导在内的各种代谢途径均显著下调。实验表明，基于临床药物的Ce-Aln凝胶通过改善炎症和抑制缺损处破骨细胞形成，有效促进了骨质疏松性骨缺损的组织修复。值得注意的是，全身性骨质疏松症得到了显著改善，突出了其在骨缺损精准治疗临床转化方面的强大潜力。
