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

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 vesicl...

Full description

Saved in:
Bibliographic Details
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
Citations: Items that this one cites
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:2041-7314
2041-7314
DOI:10.1177/20417314241257781