Extracellular Vesicle-Mimicking Nanoparticles as Advanced Drug Delivery Systems in Cartilage Tissue Engineering: A Critical Review

Articular cartilage possesses a profoundly limited capacity for self-repair, making its degeneration in conditions like osteoarthritis (OA) a major clinical challenge. Current treatments are largely palliative or involve invasive surgical procedures with significant drawbacks, such as the formation of mechanically inferior fibrocartilage. Tissue engineering has emerged as a promising alternative, yet its success is often hampered by the difficulty of delivering therapeutic agents in a controlled and sustained manner within the complex joint microenvironment. Natural extracellular vesicles (EVs), particularly those derived from mesenchymal stem cells (MSCs), have shown considerable therapeutic potential due to their innate ability to modulate cellular communication. However, their clinical translation is severely constrained by fundamental biological limitations, including low production yields, cargo heterogeneity, and inefficient loading of exogenous drugs. This review critically examines the rise of a novel bio-inspired platform: extracellular vesicle-mimicking nanoparticles (EVNs). These bio-hybrid constructs are engineered to overcome the deficiencies of natural EVs while retaining their key biological functionalities. We provide a comprehensive overview of top-down and bottom-up fabrication strategies, methods for therapeutic cargo encapsulation, and the physicochemical and biological characterization of these advanced nanocarriers. Furthermore, we synthesize preclinical evidence demonstrating the efficacy of EVNs in targeted drug delivery, immunomodulation, and the promotion of anabolic pathways essential for cartilage regeneration. Finally, we discuss the critical barriers to clinical translation—including manufacturing, quality control, and regulatory hurdles—and outline future perspectives for the development of next-generation 'smart' EVNs for cartilage tissue engineering.

کلیدواژه ها:

Cartilage ، Tissue engineering ، Extracellular vesicles ، Nanoparticles ، Drug delivery