Jing Zhaopu, Zhang Guangyang, Cai Yuanqing, Liang Jialin, Lv Leifeng, Dang Xiaoqian
The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
J Tissue Eng. 2024 Jul 24;15:20417314241257781. doi: 10.1177/20417314241257781. eCollection 2024 Jan-Dec.
Osteoarthritis (OA) is a disease that affects the entire joint. To treat OA, it may be beneficial to inhibit the activity of TGF-β in the subchondral bone. However, delivering drugs to the subchondral bone using conventional methods is challenging. In this study, we developed an extracellular vesicle delivery system. The utilization of macrophage-derived extracellular vesicles as a drug-carrying platform enables drugs to evade immune clearance and cross biological barriers. By incorporating targeting peptides on the surface of extracellular vesicles, the drug platform becomes targeted. The combination of these two factors results in the successful delivery of the drug to the subchondral bone. The study evaluated the stability, cytotoxicity, and bone targeting capability of the engineered extracellular vesicle platform (BT-EV-G). It also assessed the effects of BT-EV-G on the differentiation, proliferation, and migration of bone mesenchymal stem cells (BMSCs). Additionally, the researchers administered BT-EV-G to anterior cruciate ligament transection (ACLT)-induced OA mice. The results showed that BT-EV-G had low toxicity and high bone targeting ability both in vitro and in vivo. BT-EV-G can restore coupled bone remodeling in subchondral bone by inhibiting pSmad2/3-dependent TGF-β signaling. This work provides new insights into the treatment of OA.
骨关节炎（OA）是一种影响整个关节的疾病。为了治疗OA，抑制软骨下骨中转化生长因子-β（TGF-β）的活性可能有益。然而，使用传统方法将药物递送至软骨下骨具有挑战性。在本研究中，我们开发了一种细胞外囊泡递送系统。利用巨噬细胞衍生的细胞外囊泡作为载药平台可使药物逃避免疫清除并跨越生物屏障。通过在细胞外囊泡表面掺入靶向肽，药物平台实现了靶向性。这两个因素的结合导致药物成功递送至软骨下骨。该研究评估了工程化细胞外囊泡平台（BT-EV-G）的稳定性、细胞毒性和骨靶向能力。它还评估了BT-EV-G对骨间充质干细胞（BMSC）分化、增殖和迁移的影响。此外，研究人员将BT-EV-G给予前交叉韧带横断（ACLT）诱导的OA小鼠。结果表明，BT-EV-G在体外和体内均具有低毒性和高骨靶向能力。BT-EV-G可通过抑制pSmad2/3依赖的TGF-β信号通路恢复软骨下骨的耦合骨重塑。这项工作为OA的治疗提供了新的见解。
