Methods and strategies of bioengineered cell exosomes for the treatment of osteoarthritis

Exosomes, as nanoscale extracellular vesicles, have emerged as vital mediators of intercellular communication through the delivery of functional cargos such as proteins, lipids, DNA, and regulatory RNAs, including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and small interfering RNAs (siRNAs). Their natural biocompatibility, targeting ability, and ability to cross biological barriers make them promising therapeutic tools for osteoarthritis (OA), a degenerative joint disease characterized by cartilage degradation and chronic inflammation. In recent years, the bioengineering of exosomes has opened new avenues for enhancing their therapeutic potential in cartilage regeneration and OA treatment. This review comprehensively summarizes recent progress in exosome engineering, including the selection of parental cells, the design and targeting of exosomes, and advanced bioengineering techniques such as RNA, protein, and drug loading, as well as surface modification. We further discuss scalable approaches for exosome purification and mass production, and the incorporation of exosomes into biomaterial scaffolds or hydrogels to enable controlled release and localized delivery. In addition, we explore therapeutic strategies involving gene therapy, chemotherapy, immunotherapy, and protein therapy, highlighting the versatility of engineered exosomes in modulating inflammation, promoting chondrocyte survival, and restoring cartilage homeostasis. Emerging technologies such as synthetic exosome mimics and vexosomes are also discussed, offering insight into future directions for enhanced delivery efficiency and clinical translation. By integrating molecular biology, materials science, and therapeutic design, engineered exosomes represent a powerful platform for precision treatment of OA. This review aims to provide a theoretical foundation and practical reference for future research and clinical application in exosome-based osteoarthritis therapy.