Harnessing exosomes for advanced osteoarthritis therapy.

Exosomes are nanosized, lipid membrane vesicles secreted by cells, facilitating intercellular communication by transferring cargo from parent to recipient cells. This capability enables biological crosstalk across multiple tissues and cells. Extensive research has been conducted on their role in the pathogenesis of degenerative musculoskeletal diseases such as osteoarthritis (OA), a chronic and painful joint disease that particularly affects cartilage. Currently, no effective treatment exists for OA. Given that exosomes naturally modulate synovial joint inflammation and facilitate cartilage matrix synthesis, they are promising candidates as next generation nanocarriers for OA therapy. Recent advancements have focused on engineering exosomes through endogenous and exogenous approaches to enhance their joint retention, cartilage and chondrocyte targeting properties, and therapeutic content enrichment, further increasing their potential for OA drug delivery. Notably, charge-reversed exosomes that utilize electrostatic binding interactions with cartilage anionic aggrecan glycosaminoglycans have demonstrated the ability to penetrate the full thickness of early-stage arthritic cartilage tissue following intra-articular administration, maximizing their therapeutic potential. These exosomes offer a non-viral, naturally derived, cell-free carrier for OA drug and gene delivery applications. Efforts to standardize exosome harvest, engineering, and property characterization methods, along with scaling up production, will facilitate more efficient and rapid clinical translation. This article reviews the current state-of-the-art, explores opportunities for exosomes as OA therapeutics, and identifies potential challenges in their clinical translation.