Drohat Philip, Baron Max, Kaplan Lee D, Best Thomas M, Kouroupis Dimitrios
Department of Orthopedics, UHealth Sports Medicine Institute, Miller School of Medicine, University of Miami, Miami, FL 33146, USA.
Diabetes Research Institute, Cell Transplant Center, Miller School of Medicine, University of Miami, Miami, FL 33136, USA.
Bioengineering (Basel). 2025 May 15;12(5):525. doi: 10.3390/bioengineering12050525.
Osteoarthritis (OA) is a chronic degenerative joint disease characterized by low-grade inflammation, cartilage breakdown, and persistent pain. Despite its prevalence, current therapeutic strategies primarily focus on symptom management rather than modifying disease progression. Monoclonal antibodies and cytokine inhibitors targeting inflammatory pathways, including TNF-α and IL-1, have shown promise but remain limited by inconsistent efficacy and safety concerns. Long-acting biologic therapies-ranging from extended-release formulations, such as monoclonal antibodies and cytokine inhibitors, to gene therapy approaches-have emerged as promising strategies to enhance treatment durability and improve patient outcomes. Extracellular vesicles (EVs) have gained particular attention as a novel delivery platform due to their inherent stability, biocompatibility, and ability to transport therapeutic cargo, including biologics and immunomodulatory agents, directly to joint tissues. This review explores the evolving role of EVs in OA treatment, highlighting their ability to extend drug half-life, improve targeting, and modulate inflammatory responses. Additionally, strategies for EV engineering, including endogenous and exogenous cargo loading, genetic modifications, and biomaterial-based delivery systems, are discussed.
骨关节炎（OA）是一种慢性退行性关节疾病，其特征为低度炎症、软骨破坏和持续性疼痛。尽管其发病率很高，但目前的治疗策略主要集中在症状管理上，而非改变疾病进程。靶向包括TNF-α和IL-1在内的炎症途径的单克隆抗体和细胞因子抑制剂已显示出前景，但仍受到疗效不一致和安全性问题的限制。长效生物疗法——从缓释制剂，如单克隆抗体和细胞因子抑制剂，到基因治疗方法——已成为增强治疗持久性和改善患者预后的有前景的策略。细胞外囊泡（EVs）因其固有的稳定性、生物相容性以及将治疗性货物（包括生物制剂和免疫调节剂）直接运输到关节组织的能力，作为一种新型递送平台而受到特别关注。本综述探讨了EVs在OA治疗中不断演变的作用，强调了它们延长药物半衰期、改善靶向性和调节炎症反应的能力。此外，还讨论了EV工程策略，包括内源性和外源性货物装载、基因修饰以及基于生物材料的递送系统。
