Engineered extracellular vesicle-delivered TGF-β inhibitor for attenuating osteoarthritis by targeting subchondral bone

• Published in: Journal of tissue engineering 2024-01, Vol.15, p.20417314241257781
• Main Authors: Jing, Zhaopu, Zhang, Guangyang, Cai, Yuanqing, Liang, Jialin, Lv, Leifeng, Dang, Xiaoqian
• Format: Article
• Language: English
• Subjects: Anterior cruciate ligament; Biocompatibility; Biological effects; Bone remodeling; Cell differentiation; Cell proliferation; Cytotoxicity; Drug delivery; Drug delivery systems; Drugs; Extracellular vesicles; Immune clearance; Immunosuppressive agents; Leukocyte migration; Macrophages; Mesenchymal stem cells; Osteoarthritis; Peptides; Stem cells; Subchondral bone; Toxicity; Transforming growth factor-b; Vesicles
• ISSN: 2041-7314; 2041-7314
• DOI: 10.1177/20417314241257781

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. Graphical Abstract Mechanism of Engineered Extracellular Vesicle-Delivered TGF-β Inhibitor for Attenuating Osteoarthritis by Targeting Subchondral Bone.